Patent Docs

University of California/Berkeley et al. Authorized to File Motion Opposed to Broad Substantive Motion No. 1

By Kevin E. Noonan --

In a brief Order issued September 25, 2019, the U.S. Patent and Trademark Office's Patent Trial and Appeal Board authorized the Junior Party (the University of California, Berkeley; the University of Vienna; and Emmanuelle Charpentier; collectively, "CVC") in Interference No. 106,115 to file a motion opposing Senior Party's (the Broad Institute, Harvard University and MIT, collectively, "the Broad") Substantive Motion No. 1 pursuant to 37 CFR §41.104(a).  As explained in an earlier post (see "Broad Institute Takes Its Turn in Interference Motion Practice"), the basis of this motion is 37 C.F.R. § 41.127(a)(1) and MPEP § 2308.03(b) (interference estoppel).  If granted, the motion would resolve the interference in the Broad's favor and could possibly preclude the Junior Party from pursuing priority of invention over eukaryotic cell embodiments of CRISPR technology.

The Order sets a deadline date of October 18, 2019, for filing an opposition, and extends the page limit from 25 to 32 pages (equivalent to the extended page limit the PTAB permitted the Broad to file in its Substantive Motion No. 1.  This Order is neither unexpected nor particularly informative; any decision other than outright denial of the Broad's Substantive Motion No. 1 requires granting CVC the right to have their say (and the Broad's motion is too substantive for that to occur).  But these circumstances make possible a reprise of the outcome in the earlier interference between these parties (No. 106,048), wherein CVC will be prevented from having the opportunity to have the PTAB determine on the merits whether CVC's inventors (including recognized inventors of CRISPR, Jennifer Doudna and Emmanuelle Charpentier) or Feng Zhang et al. were the first to invent applications of CRISPR for use in eukaryotic cells.

For additional information regarding this and other related topics, please see:

• "Broad Institute Takes Its Turn in Interference Motion Practice," September 24, 2019
• "CRISPR Interference: Motion Practice," September 11, 2019
• "PTAB Redeclares CRISPR Interference and Grants Leave for Some (But Not All) of Parties' Proposed Motions," August 29, 2019
• "University of California/Berkeley Granted Yet Another CRISPR Patent," August 25, 2019
• "CRISPR Interference Parties Propose Motions," August 1, 2019
• "Sigma-Aldrich Wants Its Piece of CRISPR Pie," July 21, 2019
• "New CRISPR Interference: The Details," July 8, 2019
• "CRISPR Battle Joined Again," July 1, 2019
• "Another U.S. Patent Issued for CRISPR," April 28, 2019
• "CRISPR Patent Watch," March 12, 2019
• "Whither CRISPR? University of California/Berkeley Granted Another CRISPR Patent," October 30, 2018
• "Regents of the University of California v. Broad Institute, Inc. (Fed. Cir. 2018)," September 10, 2018
• "The CRISPR Chronicles -- Broad Institute Wins One and Loses One," January 24, 2018
• "Berkeley Files Opening Brief in CRISPR Appeal," July 31, 2017
• "University of California/Berkeley Appeals Adverse CRISPR Decision by PTAB," April 13, 2017
• "PTAB Decides CRISPR Interference in Favor of Broad Institute -- Their Reasoning," February 16, 2017
• "PTAB Decides CRISPR Interference -- No interference-in-fact," February 15, 2017

Microsoft Corporation v. Proxyconn, Inc. (Fed. Cir. 2015)

By Andrew Williams --

Earlier this week, we noted that parties wishing to challenge IPR Final Written Decisions from the PTAB on appeal to the Federal Circuit would face an uphill challenge.  However, even if that challenge is extremely difficult, it is not necessarily futile.  This was demonstrated by the Federal Circuit on June 16, 2015 when it remanded part of a PTAB decision in the Microsoft Corporation v. Proxyconn, Inc. case.  The Court held that even though it does not constitute error to use the "Broadest Reasonable Interpretation" (or BRI) standard for claim construction, it is error to adopt a construction that is "unreasonable," which the Board did for two of the construed claim terms.  Otherwise, the Court did not find error with the Board's validity determination with respect to the claims not impacted by the improperly construed claims.  The Federal Circuit also addressed, for the first time, the standards implemented by the Board for amending claims during IPR proceedings.  Specifically, the Court found that the Board's Idle Free decision included a permissible interpretation of the PTO regulations at least with respect to the burden placed on the patentee to demonstrate patentability of any claim amended in view of the prior art of record.  The Court did, however, stop short of indicating that it is proper to require the patentee to address patentability over the entirety of the prior art.

At the risk of oversimplifying the technology at issue, the patent in this case, U.S. Patent No. 6,757,717, related to decreasing traffic over the internet.  Specifically, it sought to address the problem of sending files between computers multiple times when either the original computer, or an intermediary computer, already contained a copy of the file.  Basically, the computer wishing to access a particular file (the receiver/computer) sends a request to a sender/computer that has a copy of the file.  Instead of immediately sending the file, the sender/computer calculates a "digital digest," or code (our term), that can be used to uniquely identify the file.  This code is used by the receiver/computer to determine if it already has a copy of the file on its memory.  Only if the answer is negative does the sender/computer transmit the whole file over the internet.  The patent also envisioned an intermediary "gateway" computer which would use the code to determine whether a "caching" computer had a copy of the file that could be sent to the receiver/computer.  This is demonstrated in Figure 11 from the '717 patent, which was reproduced in the opinion:

Microsoft filed two IPR petitions related to the '717 patent, each challenging different claims.  The Board joined the two proceedings, and determined that claims 1, 3, 6, 7, 9-12, 14, 22, and 23 were unpatentable as anticipated, and claims 1, 3, and 10 were additionally unpatentable as obvious.  However, claim 24 survived.  Microsoft appealed the determination that claim 24 was found to be patentable, and Proxyconn cross-appealed almost everything else.  Chief Judge Prost wrote the decision for a unanimous panel that included Judge Lourie and District Judge Gilstrap from the Eastern District of Texas sitting by designation.

Was the Use of the BRI Standard Revesable Error?

Proxyconn first challenged the Board's use of the BRI standard.  While the appeal was pending, the In re Cuozzo case was decided.  The Federal Circuit in this case said it was bound by the Cuozzo decision to approve of the use of the BRI standard.

However, the Court pointed out that even though the Board may construe the claims broadly, they may not do so unreasonably.  Therefore, for example, if the PTAB adopts a construction that is contrary to arguments made or positions taken during the original prosecution, it could be reversible error.  Moreover, "[a] construction that is 'unreasonably broad' and which does not 'reasonably reflect the plain language and disclosure' will not pass muster."  In other words, the construction cannot be divorced from the specification or the record.

Was the Construction of the Claim Terms Really "Reasonable"?               

Proxyconn next challenged the claim constructions as unreasonable.  The first related to the phrase "gateway . . . connected to said packet-switched network in such a way that network packets send between at least two other computers."  The Board adopted the construction proffered by Microsoft that the "two other computers" were not limited to just the sender/computer and the receiver/computer, but could encompass the gateway and caching computers.  As a result, it found claims 6, 7, and 9 anticipated by the "DRP" reference.

The Federal Circuit did not find this construction to be reasonable.  A plain reading of the impacted claims indicated that the "two other computers" were meant to be alternatives to the gateway and caching computers.  Indeed, the term "other" denoted distinction between the "two other computers" and the gateway and caching computers separately identified in the claims.  Therefore, a construction that included them would be nonsensical.  Furthermore, the specification consistently used this term to distinguish the two computers from the gateway and caching computers.  Therefore, the Board's construction was determined to be unreasonably broad.

Similarly, Proxyconn challenged the construction of the terms "sender/computer" and "receiver/computer."  Specifically, the Board construed these claim terms in such a way as to encompass the intermediary gateway and caching computers.  But, with similar logic as used above, the Federal Circuit found that such constructions did not reasonably reflect the language and disclosure of the '717 patent.

Because the Board's determination of patentability was necessarily flawed with regard to the claims that contained any of these claim terms, the Federal Circuit vacated the findings of unpatentability of these claims and remanded for proceedings consistent with the opinion.  Because Microsoft filed a petition for panel rehearing at the end of July, the case has not yet made its way back to the PTAB.  It will be interesting to see how they handle the remand, and how fast they handle it, once it returns.  Without the "one-year-to-final-decision" time constraints, the PTAB may not feel compelled to deal with the remand in an expedited fashion.  We will, of course, monitor the case and report any interesting developments.

Did the Board Properly Deny Proxyconn's Motion to Amend

As another interesting aspect of this case, the Federal Circuit for the first time addressed one the largest criticisms levied against the PTAB for these new post-grant proceeding challenges to issued patents -- the ability (or lack thereof) to amend the claims.  Proxyconn had moved to replace claims 1 and 3 with claims 35 and 36, respectively.  Microsoft alleged that the substitute claims were not patentable because they were anticipated by the prior art reference DRP, which was of record, but was not a reference cited when trial was instituted for these two claims.  The Board denied the motion for two reasons.  First, it found that Proxyconn had not met its burden of establishing a prima facie case of patentability.  Essentially, among other defects, it had failed to provide constructions of the newly added claim terms, failed to address the manner in which the claims were patentable over the art, and failed to identify the closest prior art.  Second, it rejected Proxyconn's argument that the Board was precluded from relying on the DRP reference.

At center stage in this appeal was the "informative" decision Idle Free, which was decided by a six-member panel.  As such, even though it is not necessarily binding on other panels, it has been cited on numerous occasions in the denial of motions to amend.  Basically, the Idle Free decision clarifies that the burden is on the patent owner to show "a patentable distinction over the prior art of record and also prior art known to the patent owner."  Interestingly, because the DRP reference was of record in the case, the Federal Circuit made clear that it was not deciding whether every requirement in Idle Free constitutes permissible interpretations of the PTO's regulations.  As indicated in footnote 4, "[t]he Idle Free decision is not itself before us . . . ."  Therefore, it remains a question whether a patentee is properly required to provide a distinction over the all of the prior art (at least of which it is aware).

But, with regard to the prior art of record, the Court found the Idle Free requirement to be reasonable.  First, it found that establishing "rules" within adjudicated cases was permissible.  While it might be advantageous to establish such rules with traditional notice and comment rule-making, the decision ultimately rests with the agency's discretion.  As such, the use of adjudication over rulemaking was not an abuse of discretion.  Second, the Court found that the Board acted reasonably when it interpreted its rules to require a patentee to show patentability over the art of record, because nothing in the statute or regulations prohibits it.  Moreover, it is consistent with the very nature of these IPR proceedings.  If the motion is granted, the claims will be added to an issued patent without further examination.  Therefore, to limit any challenge to only the art cited at institution could prevent the Board from denying the motion despite being in possession of art that undermines patentability.  Finally, the Court rejected Proxyconn's argument that such an interpretation was "fundamentally unfair."  Proxyconn was clearly aware of the DRP reference because it was a part of the entire proceedings.  It also had an opportunity to respond to Microsoft's opposition which cited the DRP reference, although it chose not to.  As such, the Court determined that this was not a case in which Proxyconn was taken by surprise and was not given the opportunity to respond.

Microsoft Corporation v. Proxyconn, Inc. (Fed. Cir. 2015)
Panel: Chief Judge Prost, Circuit Judge Lourie, and District Judge Gilstrap (sitting by designation)
Opinion by Chief Judge Prost

BPAI Seeks Further Briefing on Claim Encompassing "400 Billion Oligomers"

By Donald Zuhn --

Last week, in Ex parte DeGrado, an appeal before the Board of Patent Appeals and Interferences concerning U.S. Application No. 10/801,951 (U.S. Patent Application Publication No. US 2006/0041023), the Board issued an order calling for further briefing on two issues related to a claim that the Board "conservatively estimate[s] . . . encompasses in excess of 400 billion oligomers."  In particular, the Board is requiring Applicants to brief the following questions:

1.  Whether Applicants may be required to restrict their claims to a single invention under the provisions of 35 U.S.C. § 121.

2.  Whether Claim 16 is a proper "Markush Claim."

Aside from the issues for which the Board seeks further briefing, the appeal is notable in that the panel consists of the Commissioner of Patents.

In its order, the Board notes that claim 16 relates to a method for treating microbial infections by administering a compositions including at least one amphiphilic oligomer, and that the amphiphilic oligomers falling within the scope of the claims are defined by the formula R¹-[-x-A₁-x-y-A₂-y-]m-R² (wherein the definitions of R¹, R², x, y, A₁, A₂, and m take up three pages of the 12-page order).  Reviewing the prosecution history, the Board stated that the application as originally filed contained seven independent claims, five directed to methods of treating microbial infections by administering oligomers and two directed to groups of oligomers.  None of the originally filed claims required that the oligomers be amphiphilic.

The Examiner opened prosecution by issuing a restriction requirement that identified fifteen inventions and required Applicants to select one of the inventions as well as a single species of oligomer from the elected group.  Following Applicants' selection of the invention of Group III and a specific oligomer, the Examiner issued an additional restriction requirement for the invention of Group III that identified 28 classes of oligomers within Group III and required Applicants to select one of the classes as well as a single species of oligomer from the elected class.  Applicants responded by amending claim 16 to require that the oligomers be amphiphilic, and traversing the restriction and election requirement, in part, on the ground that it ignored the amphiphilicity feature of the invention, which Applicants explained gave the oligomers their anti-microbial property.  Applicants also argued that they could not elect one of the 28 classes of oligomers because none of the classes "permit the property of amphiphilicity, which is the central feature of Applicants' invention."  Applicants further argued that requiring a restriction between independent inventions present in a single claim is improper under In re Weber, 580 F.2d 455 (C.C.P.A. 1978) and In re Haas, 580 F.2d 461 (C.C.P.A. 1978), and that M.P.E.P. § 803.02 requires the Office to examine all claims exactly as presented by Applicants unless the claims lack "unity of invention."  Applicants contended that the recited amphiphilic oligomers demonstrated unity of invention because they share the common utility of antimicrobial activity and the structural feature of amphiphilicity.  Following Applicants' amendment of claim 16, the Examiner withdrew the earlier restriction requirements and issued a new restriction requirement that identified 21 inventions.  Applicants selected the same group of claims (16-48) and oligomer as selected in response to the initial restriction requirement, and again argued that the property of amphiphilicity common to all the claimed compounds and their effectiveness for treating microbial infections precluded restriction.  Applicants also argued the impropriety of restricting between multiple inventions in a single claim, noting that 35 U.S.C. § 121 "does not grant the PTO the authority to refuse to examine a single claimed invention."

The Board notes in its order that in Weber:

The Court held that in requiring that "[t]he specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention," 35 U.S.C. § 112, 2nd paragraph, allows the inventor to claim the invention in the way he chooses (subject to the other requirements of law), including claiming multiple independent and distinct inventions in a single claim.

However, the order "require[s] that Applicants brief the apparent conflict between the plain language of § 121 [which appears to empower the Director to require any "application to be restricted to one of the inventions"] and the Weber and Haas opinions.

Citing In re Harnisch, 631 F.2d 716, 722 (C.C.P.A. 1980), and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984), the Board states that "[a] Markush claim is improper if the inventions (1) do not share a common use; or (2) do not share a 'single structural similarity,' that is, a substantial structural feature disclosed as being essential to the common utility."  Noting that the Examiner restricted claims 16-48 into 21 inventions on the basis of "the markedly different chemical structures between the oligomers in the different groups," the Board also requires additional briefing from Applicants on whether claims 16-48 are proper Markush Claims.  In particular, the Board states that:

Applicants are required to brief whether the recitation of a broad general formula covering a very large group of compounds, the recitation of a general chemical property (amphiphilicity) that may be possessed by those compounds, and the recitation of the single broad step of "administering an effective amount" is per se sufficient to create "unity of invention" as that concept was used by the Harnisch court.

Applicants must submit their brief by June 6.

Ex parte Competitive Technologies, Inc. (B.P.A.I. 2009)

Board Finds Metabolite Claim to be Patentable

    By Kevin E. Noonan --

The most significant non-decision from the Supreme Court in recent memory is Justice Breyer's dissent over the Court's decision to dismiss its granted certiorari petition (as improvidently granted) in the Laboratory Corp. v. Metabolite Laboratories, Inc. case regarding the patent-eligibility of this claim:

13.  A method for detecting a deficiency of cobalamin or folate in warm-blooded animals comprising the steps of:  assaying a body fluid for an elevated level of total homocysteine; and correlating an elevated level of total homocysteine in said body fluid with a deficiency of cobalamin or folate.

The bases for the dissenters' objections to the patentability of this claim has been discussed in prior Patent Docs posts (see "The Supreme Court, In re Bilski and the Lingering Question of Labcorp v. Metabolite").  Today, the Board of Patent Appeals and Interferences issued its decision in an appeal from a final rejection of this claim in reexamination, reversing the Examiner's assertion that the claim was unpatentable for obviousness.

The ex parte reexamination, Control No. 90/008,305, of U.S. Patent 4,940,658 was requested on October 23, 2006, and claims 13, 15-17 and 33 were finally rejected for obviousness over the following references:

•  Refsum et al., "Radioenzymic Determination of Homocysteine in Plasma and Urine," Clinical Chemistry 34: 624-28 (1985), cited for teaching methods for determining homocysteine levels in plasma by converted total homocysteine to radiolabeled S-adenosylhomocysteine and then quantifying;

•  Kass, "Cytochemical Detection of Homocysteine in Pernicious Anemia and in Chronic Erythremic Myelosis," American Journal of Clinical Pathology 67: 53-56 (1977), cited for teaching chemical methods of homocysteine detection in permicious anemia to detect B12 deficiency, but which test showed cross-reactivity with Coenzyme A;

•  Wilcken et al., "Homocysteinemia, Ischemic Heart Disease, and the Carrier State for Monocystinuria," Metabolism 32: 363-70 (1983), cited for teaching homocysteine detection in a twin study showing different folate and B12 levels consistently detected from RBCs; and

•  Westhyyzen et al., "Plasma amino acids and tissue methionine levels in fruit bats (Rousettus aegyptiacus) with nitrous oxide-induced vitamin B12 deficiency," British Journal of Nutrition 53: 657-62 (1985), cited for showing in correlation between plasma methionine levels and vitamin B12 deficiency.

The Examiner rejected the claims in reexamination for obviousness, citing the Refsum reference as the primary reference (showing a method for detecting plasma homocysteine) combined with the other references showing a correlation with vitamin deficiency.  It would have been obvious to combine the teachings of these references, according to the Examiner, "[b]ased on the correlation between the elevated levels of homocysteine (free and/or complexed) in blood and urine samples with deficiency of cobalamin or folate taught by Kass, Wilcken . . . and Westhuyzen."

Saith the Board:  We disagree.  The panel first stated the principle, enunciated in KSR International Co. v. Teleflex Inc., requiring "some articulated reasoning with some rationale underpinning to support the legal conclusion of obviousness" (550 U.S. 398, 418 (2007)).  Here, the Board opined that the claimed invention requires assaying for "total" homocysteine, which comprises four species (homocysteine, homocystine, homocysteine-cysteine disulfides, and protein-homocysteine mixed disulfides), based on specific findings of fact, and correlating elevated levels with folate and/or vitamin B12 deficiency (without discriminating between the two).  The panel then distinguished the cited secondary references (which the Examiner used to establish the correlation between elevated homocysteine levels and vitamin deficiency) from the claimed invention.  According to the Board, Kass teaches a chemical reaction test that measures not only homocysteine (and not "total" homocysteine) but also Coenzyme A and further distinguishes between B12 and folate deficiency (contrary to the claimed invention).  The Board further opined that the ordinarily skilled worker would not have "reasonably" read the Wilcken reference as teaching a correlation between elevated total homocysteine levels and either folate or B12 deficiency, since neither twin was reliably deficient in either folate or B12.  The Westhuyzen reference does suggest a correlation between elevated plasma homocysteine and B12 deficiency, the Board conceded, but only detects homocysteine, not total homocysteine, and there is no evidence that the detected increased in homocysteine would "necessarily mean an increase in 'total' homocysteine."  In addition to these deficiencies, the Board found that none of the cited references show any correlation between plasma homocysteine levels and folate deficiency.

The Board then held that "[t]he Examiner has failed to provide a sufficient factual basis to support her conclusion of obviousness i.e. that the applied prior art teaches or suggests all of the claim limitations" (phraseology applying -- but not rigidly applying -- the traditional TSM test remaining as one option under KSR and the Patent Office Guidelines for implementing the KSR decision).

This decision cannot be appealed by the third-party requester, and at least with regard to claim 13 provides no basis for appeal by the patentee (since the patentability of this claim was affirmed in unamended fashion by the Board's decision).  It is unlikely that this determination would change Justice Breyer's mind, in any event, since he is on record as believing that:

Even were I to assume (purely for argument's sake) that claim 13 meets certain general definitions of process patentability, however, it still fails the one at issue here:  the requirement that it not amount to a simple natural correlation, i.e., a "natural phenomenon."  See Flook, supra, at 588, n. 9 (even assuming patent for improved catalytic converter system meets broad statutory definition of patentable "process," it is invalid under natural phenomenon doctrine); Diehr, 450 U. S., at 184–185 (explaining that, even if patent meets all other requirements, it must meet the natural phenomena requirement as well).

At most, respondents have simply described the natural law at issue in the abstract patent language of a "process."  But they cannot avoid the fact that the process is no more than an instruction to read some numbers in light of medical knowledge.  Cf. id., at 192 (warning against "allow[ing] a competent draftsman to evade the recognized limitations on the type of subject matter eligible for patent protection").  One might, of course, reduce the "process" to a series of steps, e.g., Step 1: gather data; Step 2: read a number; Step 3: compare the number with the norm; Step 4: act accordingly.  But one can reduce any process to a series of steps.  The question is what those steps embody.  And here, aside from the unpatented test, they embody only the correlation between homocysteine and vitamin deficiency that the researchers uncovered.  In my view, that correlation is an unpatentable "natural phenomenon," and I can find nothing in claim 13 that adds anything more of significance.

The Board's decision properly addresses the legal flaw in Justice Breyer's reasoning, as explicated by Judge Rich in In re Bergy:  the question of patent eligibility is distinct from whether an invention satisfies the statutory requirement for patentabity.  The Board has affirmed that Claim 13 is patentable; perhaps the Supreme Court will use its review of In re Bilski to address the question of whether the claim is also patent-eligible.

Ex parte Competitive Technologies, Inc. (B.P.A.I. 2009)
Panel: Administrative Patent Judges Spiegel, Adams, and Delmendo
Opinion by Administrative Patent Judge Spiegel

Ex parte Chuang (B.P.A.I. 2008)

    By Kevin E. Noonan --

The correspondence between a nucleic acid sequence and its encoded amino acid sequence is the basis for a great deal of how the U.S. Patent and Trademark Office examines biotechnology claims.  In many instances the Office treats these sequences differently.  For example, it is common practice for the Office to impose a restriction requirement between them, requiring applicants to elect to pursue examination of either nucleic acid claims or protein (amino acid sequence) claims in an application disclosing both.  Nucleic acid claims encompassing all of the nucleic acids encoding an amino acid sequence are typically granted, while amino acid sequence variants have become increasingly more difficult to obtain, based in part on the unpredictability of the effects of variants on biological activity.

In the recent non-precedential decision by the Board, Ex parte Chuang, the Office affirmed rejection under 35 U.S.C. § 102(b) of claims to an isolated protein over prior art disclosing a nucleic acid encoding the protein.  The rejected claims were directed to the isolated polypeptide:

Claim 4.  An isolated polypeptide, comprising the amino acid sequence of SEQ ID NO: 1.

Claim 20.  An isolated polypeptide, comprising a sequence that has at least 95% sequence identity to SEQ ID NO: 1, wherein the polypeptide reduces 15-keto prostaglandin but does not reduce leukotriene B4.

The Office cited three prior art references, directed towards large collections of isolated and sequenced mouse cDNA sequences.  These references disclosed the amino acid sequence encoded by the cDNA and identified it as a member of a zinc-containing alcohol dehydrogenase superfamily.  The references did not produce the encoded protein nor did they identify the biochemical activity of the protein encoded by the sequence.  Nevertheless, the Board affirmed the Examiner's rejection that disclosure in the prior art of a nucleic acid that encodes a protein isolated thereafter anticipates the protein, even if the cited art did not disclose the isolated protein.

The Board distinguished over an earlier Board decision, Lee v. Dryja, 79 U.S.P.Q.2d 1614 (B.P.A.I. 2005), holding that a "cDNA is at most an equivalent of its encoded protein but does not contain every element of the isolated protein encoded thereby."  Moreover, the Lee case further held:

[A]ssuming arguendo that it was well within ordinary skill in the art to prepare, isolate and purify the protein product of a given cDNA clone at the time the '163 application [the patent application at issue] was filed, the 4.7 kb cDNA described in the '163 specification would have made its encoded protein obvious at best.

The Board based its reasoning on In re Donohue, 766 F.2d 531 (Fed. Cir. 1985), which held that "[i]t is not, however, necessary that an invention disclosed in a publication shall have actually been made in order to satisfy the enablement requirement."  Accordingly, the Board reasoned that the references cited by the examiner provided an enabling disclosure of the protein encoded by the disclosed nucleic acids, and were anticipating.  The Board noted that the burden is on applicants to establish that the cited art is not enabling.

Specifically with regard to the Lee case, the Board first noted that Lee was an interference case, and the issue decided therein was whether Dryja had produced sufficient evidence that it had possession of a single enabled embodiment within the scope of the interference count.  This standard for interferences differs from the standard for anticipation, said the Board, although here that statement seems in error:  the Board would have been in the same position with regard to the cited references if each had only enabled the embodiment identified as SEQ ID NO: 1.  Second, the Board noted that Dryja did not disclose a complete coding sequence for the protein at issue in the interference count.  In that case, the presence of a translation stop codon in the cDNA prevented Dryja's cDNA from expressing full length protein.  None of the references cited against applicants in this case suffered from this infirmity, and it was undisputed that the cDNA could have (but had not) been used to produce the claimed protein.

While non-precedential, this case illustrates that the Office will now consider disclosed nucleic acids to be anticipating references to claims for isolated polypeptides.  This attitude has far-reaching implications for biotechnology, in view of the extensive public disclosure and annotation of open reading frames in sequences determined by the Human Genome Project.  It also contrasts starkly with the more stringent utility requirement for claiming such sequences, wherein applicants must show possession of not only the isolated nucleic acid and expressed protein thereof but also a specific, substantial, and credible utility for nucleic acids and proteins.  Thus, the Office imposes a standard of knowing the function of a protein encoded by a nucleic acid, but considers the mere disclosure of the nucleic acid to anticipate not only the nucleic acid but the protein encoded thereby.  Under these circumstances, it is likely that no later-filed claims to proteins encoded by open reading frames identified from the Human Genome Project will be patented, even if the protein has a unique, unappreciated biological activity.  This stance by the Office will put to the test the belief by many in the biotechnology community that patent protection is necessary to obtain investment in technologies derived from the explosion of genetic information that even now has not been completely elucidated, and that the absence of patent protection will retard if not preclude such investment.  It may be an expensive lesson to learn.

Ex parte Chuang (B.P.A.I. 2008)
Panel: Administrative Patent Judges Grimes, Lebovitz, and Fredman
Opinion by Administrative Patent Judge Fredman

Genetic code image: Madprime, Wikipedia Commons, GNU Free Documentation License

In re Kubin to Be Argued before the Federal Circuit on Thursday

    By Kevin E. Noonan --

The Federal Circuit will hear oral argument on Thursday for In re Kubin, a case having great significance for biotechnology patenting.  At issue is the question of whether the existence in the prior art of a purified protein, combined with "routine" cloning methods, renders obvious a claim to a nucleic acid encoding the protein.  This was the Patent Office position twelve years ago, which was rejected by the Federal Circuit in the In re Bell and In re Deuel decisions.  But the Supreme Court's KSR Int'l Co. v. Teleflex Inc. decision emboldened the Patent Office to challenge the Federal Circuit on this issue.  As a bonus, the Court will also be asked to opine on how the Office has interpreted its frequently-conflicting written description jurisprudence.

To recap, the case involved an application claiming an isolated cDNA encoding Natural Killer Cell Activation Inducing Ligand (abbreviated as NAIL).  The Board determined that all the claims would stand or fall together, since they were not argued separately; accordingly, its analysis was confined to claim 73:

73.  An isolated nucleic acid molecule comprising a polynucleotide encoding a polypeptide at least 80% identical to amino acids 22-221 of SEQ ID NO:2, wherein the polypeptide binds CD48.

The Board cited three prior art references, including (1) Valiante, which identified the existence of a protein, p38, present on the cell surface of natural killer cells and a monoclonal antibody specific for p38; and (2) Sambrook et al., a standard reference work describing gene cloning techniques (otherwise known as the "Maniatis manual").  The Valiante reference contained a prophetic example to the effect that the gene encoding the p38 protein could be isolated using methods such as those disclosed in Sambrook et al.  The Board considered but did not rely upon a reference to Matthews, which disclosed a mouse protein, 2B4, expressed on the cell surface of natural killer cells (2B4 is the mouse ortholog of human p38 although that was not disclosed in the art).  The Board stated that it found Matthews "cumulative" of the teachings of Valiante and Sambrook et al.; nevertheless, it used this reference as an "illustration" of how a gene could be isolated.  The evidence from the applicants' specification was that their NAIL cDNA clones were produced using an expression library screened with a commercially-available monoclonal antibody against human p38.

The Board based its factual determinations on the notion that the art had progressed since the time Deuel was decided.  These differences included:

1.  In Kubin, a cell "unambiguously" (see below) expressing the gene was known; in Deuel, the cloned gene was isolated from a cDNA library prepared from placenta, even though the protein encoded thereby was expressed specifically in brain.

2.  In Kubin, the art provided an isolated preparation of the cognate protein and a monoclonal antibody that binds to the protein; in Deuel, the art disclosed isolated preparations of three different brain-specific proteins but no antibodies.

3.  In Kubin, the art provided a monoclonal antibody specific for the gene product of the desired cDNA and thus providing a specific probe; in Deuel, the probes were a plurality of degenerate oligonucleotides prepared from the partial amino-terminal amino acid sequences.

4.  In Kubin, the art has developed expression cloning technology and provided an antibody probe specific for the gene product of the desired clone; in Deuel, the absence of a specific antibody precluded use of expression cloning technology.

Even if the Board was correct in considering these factual distinctions, the Board's decision demonstrated that it did not learn the fundamental lesson from the Federal Circuit's decision in Deuel:  that the obviousness of a method for producing a cloned nucleic acid is not sufficient to render obvious the cDNA itself.  Rather, the Board attempted to apply the Supreme Court's statements from KSR regarding the obviousness of what is "obvious to try."  Expressly citing the Supreme Court's language:

When there is motivation to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp.  If this leads to anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.  In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.  KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, ___, 82 USPQ2d 1385, 1397 (2007).

the Board opined, "[t]his reasoning is applicable here."  The Board then went on to state:

The "problem" facing those in the art was to isolate NAIL cDNA, and there were a limited number of methodologies available to do so.  The skilled artisan would have had reason to try these methodologies with the reasonable expectation that at least one would be successful.  Thus, isolating NAIL cDNA was "the product not of innovation but of ordinary skill and common sense," leading us to conclude NAIL cDNA is not patentable as it would have been obvious to isolate it.

Using this reasoning as its basis, the Board showed its willingness to continue to conflate whether the method for making a cDNA such as the NAIL cDNA would be obvious with the obviousness of the cDNA itself.  This is consistent with the reasoning, and the mistakes, made by the Board in Deuel:

The PTO's focus on known methods for potentially isolating the claimed DNA molecules is also misplaced because the claims at issue define compounds, not methods.  See In re Bell, 991 F.2d 781, 785, 26 USPQ2d 1529, 1532 (Fed. Cir. 1993).  In Bell, the PTO asserted a rejection based upon the combination of a primary reference disclosing a protein (and its complete amino acid sequence) with a secondary reference describing a general method of gene cloning.  We reversed the rejection, holding in part that "the PTO's focus on Bell's method is misplaced.  Bell does not claim a method.  Bell claims compositions, and the issue is the obviousness of the claimed compositions, not of the method by which they are made."  Id.

We today reaffirm the principle, stated in Bell, that the existence of a general method of isolating cDNA or DNA molecules is essentially irrelevant to the question whether the specific molecules themselves would have been obvious, in the absence of other prior art that suggests the claimed DNAs.  . . .  There must, however, still be prior art that suggests the claimed compound in order for a prima facie case of obviousness to be made out; as we have already indicated, that prior art was lacking here with respect to claims 5 and 7.  Thus, even if, as the examiner stated, the existence of general cloning techniques, coupled with knowledge of a protein's structure, might have provided motivation to prepare a cDNA or made it obvious to prepare a cDNA, that does not necessarily make obvious a particular claimed cDNA.  "Obvious to try" has long been held not to constitute obviousness.  In re O'Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1680-81 (Fed. Cir. 1988).  A general incentive does not make obvious a particular result, nor does the existence of techniques by which those efforts can be carried out.  Thus, Maniatis's teachings, even in combination with Bohlen, fail to suggest the claimed invention.

The problem with the Board's analysis is that KSR requires a "finite number of identified, predictable solutions" (something that does not apply to nucleic acids and which was the basis for the Federal Circuit's decisions in In re Deuel and In re Bell).  Such a "finite number" of "identified, predictable" solutions were not known in the prior art cited by the Board.

An important factor discounted by the Board comes from the disclosure of the Matthews reference, relating to the isolation of the mouse ortholog of the human NAIL cDNA.  This reference was not considered by the Board, which seemed to recognize that the art did not teach that p38 was the mouse ortholog of NAIL.  Moreover, the Matthews reference contained Northern blot experiments (for detecting mRNA expression of NAIL) from human cells and tissues indicating that NAIL expression could not be detected in the immune cell types that applicants used for cloning the human NAIL cDNA.  The Board thus ignored evidence in the art that reduced the likelihood that the human NAIL cDNA could be isolated using the methods disclosed in the Sambrook et al. reference, since the art taught that human cells that actually expressed the NAIL cDNA did not do so.  This is an important distinction with Deuel:  in that case the gene was isolated from a tissue where its expression was not expected, while in Kubin the art taught affirmatively that the gene was not expressed in the tissue source of the cDNA used by applicants.

The other issue to be decided by the Federal Circuit involves the Board's decision to affirm the Examiner's determination that the application failed to satisfy the written description requirement for claims reciting nucleic acids encoding proteins at least 80% identical to the disclosed amino acid sequence of the claimed human NAIL protein.  The Board held that Kubin was not entitled to a claim to an isolated nucleic acid encoding a protein having 80% identity to the disclosed amino acid sequence and that bound to CD48.  Kubin's specification disclosed the amino acid sequence of the protein encoded by the NAIL gene, as well as domains of the protein (signal peptide, extracellular domain, transmembrane domain, and cytoplasmic domain), including the portion of the protein that bound to CD48 (amino acids 22-221).  The specification also disclosed conservative substitutions of these sequences, in addition to deletions, insertions, and fusions.  These teachings were generic, however, and no specific amino acid sequence variants were disclosed.  The Board held that the absence of any specifically-disclosed variants was a failure to satisfy the written description requirement and upheld rejection on these grounds.

The Federal Circuit's decision on the written description issue may be at least as important as its determination of what is non-obvious, since it presents a question not yet squarely put to the Federal Circuit.  The Federal Circuit has developed its written description jurisprudence (in Regents of the University of California v. Eli Lilly & Co., Enzo Biochem, Inc. v. Gen-Probe Inc., and University of Rochester v. G.D. Searle & Co.) generally in the context of patent infringement litigation and, except for dicta in its second Enzo decision, has not had the opportunity to provide guidance to the Office on how (or whether) its Guidelines are properly applying the Court's case law.  The Patent Office has applied its Guidelines to effectively preclude an applicant from claiming "conservative substitutions," on the basis that there was no disclosure of a "representative number of species."  (Of the 8,367 issued U.S. patents reciting "isolated" and "nucleic acid" in the claims, only 20 contain the term "conservative substitution.")  It has become clear that the Office's use of the Guidelines would prevent an applicant from ever disclosing a sufficient number of substitutions that the Office would consider "representative" based on the type of generic disclosure set forth in Kubin's specification, and that it was impractical if not impossible to comply with the Office's requirements.  The Office appears to have extended the Federal Circuit's requirement that structural domains important for biological activity be identified, to require that an applicant identify which amino acid residues can be modified and which cannot.  This is a clear extension of the analysis set forth in Eli Lilly that has no support in any Federal Circuit decision.  Yet, the Office routinely refuses to allow claims containing "conservative substitutions" within their scope.  In re Kubin puts the question squarely before the Federal Circuit for the first time.

Patent Docs will provide a synopsis of the argument in a subsequent post.

For information regarding this and other related topics, please see:
• "Docs at BIO: Panel Discusses IP Strategies after KSR," June 26, 2008
• "Docs at BIO: 'Gotcha' Games Continue at USPTO," June 25, 2008
• "Docs at BIO: Representatives from JPO, EPO, SIPO, and USPTO Discuss Recent Developments in Japan, Europe, China, and the U.S.," June 22, 2008
• "Briefs for In re Kubin filed by Amgen and BIO," June 12, 2008
• "USPTO's Bruce Kisliuk Addresses ACI Conference," March 3, 2008
• "DNA Non-obviousness under Ex parte Kubin (It Gets Worse)," October 18, 2007
• "Ex parte Kubin (B.P.A.I. 2007)," July 18, 2007

The Written Description Training Materials and Ex parte Porro

    By Donald Zuhn --

Last month, we reported on a presentation that Dr. George Elliott, Group 1600 Director of the U.S. Patent and Trademark Office, gave at this year's BIO International Convention (see "Docs at BIO: Representatives from JPO, EPO, SIPO, and USPTO Discuss Recent Developments in Japan, Europe, China, and the U.S." and "Docs at BIO: "Gotcha" Games Continue at USPTO").  Among the topics that Dr. Elliott addressed during his presentation were the new written description training materials -- specifically, Example 11, which concerns claims directed to a polynucleotide or polypeptide sequence that shares percent identity with another sequence.

As we noted in an earlier report, Example 11 seems to suggest that the recitation of a functional limitation can render an otherwise allowable claim unallowable (see "An Analysis of the New Written Description Training Materials - DNA Hybridization & Percent Identity").  In particular, Example 11 introduces the following exemplary claims:

Claim 1:  An isolated nucleic acid that encodes a polypeptide with at least 85% amino acid sequence identity to SEQ ID NO: 2.

Claim 2:  An isolated nucleic acid that encodes a polypeptide with at least 85% amino acid sequence identity to SEQ ID NO: 2; wherein the polypeptide has activity X.

Example 11 concludes that despite the specification's disclosure of only a single species encoding the polypeptide of SEQ ID NO: 2 (i.e., SEQ ID NO: 1), and the lack of any teaching in the specification regarding which amino acid residues in SEQ ID NO: 2 are tolerable to change, the specification satisfies the written description requirement with respect to claim 1 (because a skilled artisan could use a computer to identify all of the nucleic acids encoding a polypeptide sharing at least 85% sequence identity with SEQ ID NO: 2), but not claim 2 (because the specification lacks any teaching of the residues associated with the recited function).

During his BIO presentation, Dr. Elliott noted that with respect to the situation presented in Example 11, the USPTO had reversed its position, having previously asserted that claims lacking functional language failed to comply with the written description requirement and that claims possessing such language complied with the requirement.  According to Dr. Elliott, claims with functional language (where the specification lacks any teaching regarding the amino acid residues that are tolerable to change) do not satisfy the written description requirement because "the minute you add function, you've limited the claim to a subset of species, and you don't know which species are in the subset and which species aren't."  In other words, absent any teaching of structure/function relationships, the USPTO's (and Dr. Elliott's) position is that one cannot determine the species that share at least 85% sequence identity with the recited sequence and also possess the recited function (this explanation does not, of course, take into account case law that allows for the recitation of a genus containing some inoperative species).

Dr. Elliott also acknowledged that Example 11 may be a little disingenuous in that it appears to suggest that an applicant would be better off omitting a functional limitation from a claim.  However, he pointed out that this example includes the following practice note:

Dr. Elliott informed session attendees that just because claim 1 in Example 11 satisfied the written description requirement, this does not mean that the claim would necessarily satisfy the enablement and utility requirements.  For a more thorough discussion of the rationale behind the USPTO's reversal on functional limitations, Dr. Elliott recommended that attendees read the decision in Ex parte Porro.  We decided to take Dr. Elliott's advice.

In Porro, which was decided last March, the Board of Patent Appeals and Interferences affirmed the Examiner's determination that claims to a method of making ascorbic acid (vitamin C) lacked an adequate written description.  Claims 12-14 were at issue on appeal; representative claim 13 recites:

13.  A method of generating ascorbic acid, comprising:
    a) obtaining a recombinant yeast capable of converting an ascorbic acid precursor into ascorbic acid, wherein the yeast is functionally transformed with a coding region encoding L-galactose dehydrogenase (LGDH) enzyme having at least about 90% identity with SEQ ID NO: 11,
    b) culturing the recombinant yeast in a medium comprising an ascorbic acid precursor, thereby forming ascorbic acid, and
    c) isolating the ascorbic acid.

During prosecution of the claims at issue, the Examiner noted that the specification disclosed only a single LGDH sequence (i.e., SEQ ID NO: 11), which the inventors had obtained from Arabidopsis thaliana.  The Examiner also noted that the prior art failed to disclose other LGDH enzymes sharing 90% identity to SEQ ID NO: 11.  Concluding that the claims encompassed a very large genus of sequences and that the specification and prior art provided a limited description of the motifs or structures responsible for LGDH activity, the Examiner determined that the specification did not adequately describe the genus of "L-galactose dehydrogenase (LGDH) enzyme[s] having at least about 90% identity with SEQ ID NO: 11."

The Board affirmed the Examiner's determination that claims 12-14 lacked an adequate written description, citing University of California v. Eli Lilly and Co., 119 F.3d 1559 (Fed. Cir. 1997) and University of Rochester v. G.D. Searle & Co., 358 F.3d 916 (Fed. Cir. 2004) in support of its decision.  With respect to Eli Lilly, the Board determined that "[t]he Eli Lilly court held that a fully described genus is one for which a person skilled in the art can 'visualize or recognize the identity of the members of the genus,'" and in the instant case, "the Specification does not provide guidance regarding what structural features are responsible for the enzymatic activity of LGDH, nor does it describe what amino acid changes can be made in the wild-type sequence without affecting the enzymatic activity of the protein."  The Board concluded that "the Specification does not describe the recited genus adequately for those skilled in the art to distinguish the SEQ ID NO: 11 variants that are within the claims from other variants of SEQ ID NO: 11," and therefore, "does not adequately describe the recited genus under the standard of Eli Lilly."

With respect to University of Rochester, the Board stated that:

Just as in University of Rochester, the present application discloses a genus of chemical compounds (proteins having amino acid sequences at least 90% identical to SEQ ID NO: 11).  According to Appellants’ calculations, the genus encompasses 3.4 x [ten to the power of 41] different proteins.  But the claims are limited to only those compounds having a desired characteristic (having LGDH enzymatic activity).  Just as in University of Rochester, the present Specification does not guide the skilled artisan to the subset of proteins within the genus of 3.4 x [ten to the power of 41] proteins that are at least 90% identical to SEQ ID NO: 11 that have the recited enzymatic activity.

In affirming the Examiner's rejection, the Board concluded that a subgenus of "functional variants" within a genus of "variants" must be described by disclosing a representative number of functional variants or by disclosing "structural features that are common to functional variants that distinguish them from the rest of the genus (i.e., structural features that correlate with enzymatic activity regardless of other variations from SEQ ID NO: 11)," and that the application at issue provided neither.  Interestingly, the Board conceded that there may be other ways to describe such a subgenus, but that "the case law is a little hazy in this area."

While the Written Description Training Materials (which were published in late March) do not mention the Porro case by name, the language of Example 11 leaves little doubt that Porro (which was decided March 11) served as the basis for Example 11.  For example, the Board states that:

Certainly SEQ ID NO: 11 is adequately described.  We can also assume, for present purposes, that a description of SEQ ID NO: 11 is adequate to describe amino acid sequences that are 90% identical to SEQ ID NO: 11[.]  Given a computer and sequence-comparison software, a skilled artisan may well be able to visualize or recognize the identity of members of that genus.

The Board's conclusion and reasoning in Porro is nearly identical to that provided by the Training Materials for exemplary claim 1 (including statements about using a computer to identify sequence variants).

Moreover, the Board's response to the applicants' argument that "[t]he skilled artisan would have a reasonable expectation that an LGDH . . . would be operable in the claimed methods" evokes Example 11's Practice Note.  In particular, the Board stated that such an argument was not directed to the issue raised on appeal since the Examiner had not made an enablement rejection.  In view of the decision in Porro and the new Training Materials, it will be interesting to see how the Patent Office balances the issues of operability and enablement with respect to pending claims that resemble exemplary claim 1 of Example 11 (particularly since Judge Lourie did not find these issues to present a problem for hybridization variants in Enzo Biochem, Inc. v. Gen-Probe Inc., 296 F.3d 1316 (Fed. Cir. 2002)).

Ex parte Porro (B.P.A.I. 2008)
Panel: Administrative Patent Judges Scheiner, Mills, and Grimes
Opinion by Administrative Patent Judge Grimes

Ex parte Kubin (B.P.A.I. 2007)

    By Kevin E. Noonan --

The Board of Patent Appeals and Interferences recently got its long awaited opportunity to opine on the continued validity of the Federal Circuit's In re Deuel decision in light of the Supreme Court's recent decision in KSR Int'l Co. v. Teleflex Inc.  Deuel is widely acknowledged (and decried in the Patent and Trademark Office) as settling "once and for all" (or at least until now) that isolation of a nucleic acid encoding a "known" gene is nonobvious.

The case, Ex parte Kubin, involved an application for isolated cDNA encoding Natural Killer Cell Activation Inducing Ligand (abbreviated as NAIL).  The Board affirmed the Examiner's rejection based on prior art including U.S. Patent No. 5,688,690, disclosing the human NAIL gene product (p38), methods for producing a cDNA encoding p38, a scientific journal article disclosing the nucleotide sequence of the mouse ortholog, and that old stand-by, the Maniatis cloning manual (Sambrook et al.).  The evidence from the applicants' specification was that their NAIL cDNA clones were produced using an expression library screened with a commercially-available monoclonal antibody against human p38.

The Board correctly noted that the art had progressed since the time Deuel was decided.  Indeed, there are at least the following differences between the factual situation in Kubin and Deuel:

1.  In Kubin, a cell "unambiguously" (see below) expressing the gene was known; in Deuel, a protein that the prior art taught was expressed in brain was cloned from placenta.

2.  In Kubin, the nucleotide and amino acid sequence of the mouse ortholog of human NAIL was known; in Deuel, the prior art disclosed three different brain-specific proteins and a partial amino-terminal amino acid sequence thereof.

3.  In Kubin, the art provided an isolated preparation of the cognate protein and a monoclonal antibody that binds to the protein; in Deuel, the art disclosed isolated preparations of three different brain-specific proteins but no antibodies.

4.  In Kubin, the art provided a monoclonal antibody specific for the gene product of the desired cDNA and thus providing a specific probe; in Deuel, the probes were a plurality of degenerate oligonucleotides prepared from the partial amino-terminal amino acid sequences.

5.  In Kubin, the art has developed expression cloning technology and provided an antibody probe specific for the gene product of the desired clone; in Deuel, the absence of a specific antibody precluded use of expression cloning technology.

Despite these valid reasons for coming to a different conclusion in Kubin than the Federal Circuit mandated in Deuel, the Board in dicta shows that it has still not learned, or refuses to acknowledge the teachings of In re Deuel.  In attempting to apply the Supreme Court's teachings from KSR, the Board cites the decision's dicta on the application of the principle of "obvious to try":

When there is motivation to solve a problem and there are a finite number of identified, predictable solutions, a person of ordinary skill has good reason to pursue the known options within his or her technical grasp.  If this leads to anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.  In that instance the fact that a combination was obvious to try might show that it was obvious under § 103.

KSR Int'l Co. v. Teleflex Inc., 127 S. Ct. 1727, ___, 82 USPQ2d 1385, 1397 (2007).  This reasoning is applicable here.

While this is an accurate statement of the Supreme Court's dicta, the Board misapplies it.  The Board goes on to state:

The "problem" facing those in the art was to isolate NAIL cDNA, and there were a limited number of methodologies available to do so.  The skilled artisan would have had reason to try these methodologies with the reasonable expectation that at least one would be successful.  Thus, isolating NAIL cDNA was "the product not of innovation but of ordinary skill and common sense," leading us to conclude NAIL cDNA is not patentable as it would have been obvious to isolate it.

Thus, the Board continues to conflate whether the method for making a cDNA such as the NAIL cDNA would be obvious with the obviousness of the cDNA itself.  At least they are consistent; this is the same mistake that the Board made in Deuel:

The PTO's focus on known methods for potentially isolating the claimed DNA molecules is also misplaced because the claims at issue define compounds, not methods.  See In re Bell, 991 F.2d 781, 785, 26 USPQ2d 1529, 1532 (Fed. Cir. 1993).  In Bell, the PTO asserted a rejection based upon the combination of a primary reference disclosing a protein (and its complete amino acid sequence) with a secondary reference describing a general method of gene cloning.  We reversed the rejection, holding in part that "the PTO's focus on Bell's method is misplaced.  Bell does not claim a method.  Bell claims compositions, and the issue is the obviousness of the claimed compositions, not of the method by which they are made."  Id.

We today reaffirm the principle, stated in Bell, that the existence of a general method of isolating cDNA or DNA molecules is essentially irrelevant to the question whether the specific molecules themselves would have been obvious, in the absence of other prior art that suggests the claimed DNAs.  . . .  There must, however, still be prior art that suggests the claimed compound in order for a prima facie case of obviousness to be made out; as we have already indicated, that prior art was lacking here with respect to claims 5 and 7.  Thus, even if, as the examiner stated, the existence of general cloning techniques, coupled with knowledge of a protein's structure, might have provided motivation to prepare a cDNA or made it obvious to prepare a cDNA, that does not necessarily make obvious a particular claimed cDNA.  "Obvious to try" has long been held not to constitute obviousness.  In re O'Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1680-81 (Fed. Cir. 1988).  A general incentive does not make obvious a particular result, nor does the existence of techniques by which those efforts can be carried out.  Thus, Maniatis's teachings, even in combination with Bohlen, fail to suggest the claimed invention.

This analysis has not been overturned by KSR (see "Trying to Understand What's Not Obvious about What's 'Obvious to Try'").  The problem with the Board's analysis is that KSR requires a "finite number of identified, predictable solutions" which does not apply to nucleic acids (and which was the basis for the Federal Circuit's decisions in In re Deuel and In re Bell).  The Board continues to conflate the obviousness of a method for isolating a cDNA with obviousness of the cDNA isolated.  Insofar as the applicants were claiming a method of isolating the cDNA, it may be obvious.  But that isn't what they are claiming, and there is nothing in KSR that mandates the result provided by the Board.  And KSR does not stand for the proposition that the "finite number of solutions" is that the invention either will work, or it won't.

An important factor discounted by the Board comes from the disclosure of the Mathew reference, relating to the isolation of the mouse ortholog of the human NAIL cDNA.  As urged by the applicants, the Mathew reference showed the results of Northern blot experiments (for detecting mRNA expression of NAIL) from human cells and tissues; these results indicated that NAIL expression could not be detected in the immune cell types that applicants used for cloning the human NAIL cDNA.  The Board thus ignored evidence in the art that reduced the likelihood that the human NAIL cDNA could be isolated using the methods disclosed in the Sambrook reference, since the art taught that human cells that actually expressed the NAIL cDNA did not do so. KSR did not negate the impact of affirmative evidence that would teach away from an invention, or would teach the skilled worker than an invention would not work.

There is some good news in the decision regarding the requirements for enablement under § 112, first paragraph.  The Board now recognizes that merely routine experimentation is required to enable the full scope of applicants' claims, which recited nucleic acids encoding proteins at least 80% identical to the disclosed amino acid sequence of the claimed human NAIL protein.  Thus, claims having scope broader than the exact amino acid or nucleotide sequence disclosed should not be rejected under the enablement requirement of 35 U.S.C. § 112, first paragraph.  With regard to the written description requirement, on the other hand, the Board affirmed the Examiner's determination that the application failed to satisfy the written description requirement due to the lack of any disclosure of which residues could be changed or any structure/function relationships that would inform the skilled worker about which residues could (and which should not) be changed.

This first foray in the Patent and Trademark Office's application of the rubrics of KSR to patentability of nucleic acid sequences is not really a surprise, in view of the animus with which the examining corps continues to hold the decision (see, e.g., Kintisch, "Patent Experts Hope High Court Will Clarify What's Obvious," Science 314:1230-31).  However, and fortunately, the multiple factual distinctions between the Kubin case and In re Deuel should limit the applicability of the decision.

Ex parte Kubin (B.P.A.I. 2007)
Precedential opinion
Panel: Chief Administrative Patent Judge Fleming and Administrative Patent Judges Gron, Scheiner, Grimes, and Linck
Opinion by Administrative Patent Judge Linck

Patent Docs would like to thank Patently-O for bringing this decision to their attention; additional information regarding this case can be found at Patently-O.

Ex parte Levi (B.P.A.I. 2006)

    By Mark Chael --

On November 24, 2006, the Board of Patent Appeals and Interferences (BPAI) at the U.S. Patent and Trademark Office affirmed the examiner's rejection of the pending claims in U.S. Patent App. No. 10/305,577 (U.S. Patent App. Publication No. 2004/0101613) based on obviousness.  The invention disclosed in the application relates to water-oil-water (w/o/w) emulsions "that are microbiologically stable and free of a distinct sour taste" (see Abstract).  The application is assigned on its face to Unilever Bestfoods North America.

The examiner had rejected the pending claims in view of U.S. Patent No. 4,447,464 to Schwartz & Cornwell, U.S. Patent No. 4,882,187 to Izzo et al., and Schwartzberg, H.G. (1992) Physical Chemistry of Foods, Inst. of Food Technologists, ed., pp. 264-65.

In affirming the examiner's rejection, the Board cited In re Woodruff, 919 F.2d 1575 (Fed. Cir. 1990), and In re Aller, 220 F.2d 454 (C.C.P.A. 1955), for the proposition that "it is well settled that where patentability is predicated upon a change in a condition of a prior art composition, such as a change in concentration or the like, the burden is on the applicant to establish with objective evidence that the change is critical, i.e., it leads to a new, unexpected result," which the Board contended the appellant had not done in this case.

Furthermore, the Board relied on In re Merck & Co., 800 F.2d 1091 (Fed. Cir. 1986), in finding that the appellant had not established on the available record that the data in the specification relating to a claimed unexpected result or benefit "would be considered truly unexpected by one of ordinary skill in the art, especially in light of [the prior art] disclosure."  The Board contended that the appellant had offered no analysis of the available data; apparently leaving it to the Board to analyze the data in the specification and interpret that data in the appellant's favor.  The Board reminded the appellant "that the burden of showing unexpected results rests on the party asserting them" (see In re Klosak, 455 F.2d 1077 (C.C.P.A. 1972)).

Ex parte Levi (B.P.A.I. 2006)
Panel:  Administrative Patent Judges Kimlin, Timm, and Gaudette
Opinion by Administrative Patent Judge Kimlin

Bergsma vs. Sutcliffe (B.P.A.I. 2006)

    By Mark Chael --

On November 22, 2006, the Board of Patent Appeals and Interferences (BPAI) at the U.S. Patent and Trademark Office decided a patent interference in favor of Prof. J. Gregor Sutcliffe and colleagues at the Scripps Research Institute related to hypocretins.

Hypocretins are a recently discovered family of neuropeptide hormones comprising Hcrt 1 and Hcrt 2, derived from a common precursor protein.  They are synthesized by neurons located in the hypothalamus and may act in the CNS as neurotransmitters, including possible roles in nutritional homeostasis and narcolepsy, among others.

The interference was originally requested on December 12, 2000, in U.S. Patent App. No. 09/735,138 titled "Hypothalamus-Specific Polypeptides," however the USPTO and the applicants had to come to terms on allowable claims before the interference could be declared, a process which took about three years.

Previously, on December 14, 1999, Drs. Bergsma and Yanagisawa, the junior parties in the interference, were awarded U.S. Patent No. 6,001,963, which is titled "Ligands of the Neuropeptide Receptor HFGAN72."  That patent is assigned on its face to SmithKline Beecham Corporation and the University of Texas Southwestern Medical Center at Dallas.

In the interference, Drs. Bergsma and Yanagisawa filed a concession of priority, thereby prompting the Board to rule in favor of Dr. Sutcliffe and colleagues.  It was also noted by the Board that a settlement agreement existed between the parties and the Board directed the parties' attention to 35 U.S.C. § 135(c) and 37 C.F.R. § 41.205(a).  The Board ordered that the inventors were not entitled to claims 1 and 3 of the '963 patent, which corresponded to the only count in the interference (Count 2).

Bergsma v. Sutcliffe (B.P.A.I. 2006)
Panel: Administrative Patent Judges Schafer, Medley, and Moore
Opinion by Administrate Patent Judge Moore

Ex parte Bandman (B.P.A.I. 2004)

    By Donald Zuhn --

In an appeal from a final rejection of claims 3, 6, 7, 9, and 12 of U.S. Application No. 09/915,694, the Board of Patent Appeals and Interferences reversed the rejection of the claims under both the written description and enablement requirements of 35 U.S.C. § 112, first paragraph, and entered a new ground of rejection under 35 U.S.C. § 112, second paragraph, for claim 12.

Claims 3 and 12 of the '694 application, which were representative of the subject matter on appeal, recite, inter alia, an isolated polynucleotide encoding a polypeptide comprising a naturally occurring amino acid sequence at least 95% identical to the amino acid sequence of SEQ ID NO: 1 (claim 3) and an isolated polynucleotide comprising a naturally occurring polynucleotide sequence at least 95% identical to the polynucleotide sequence of SEQ ID NO: 2 (claim 12).

The Examiner had rejected claims 3, 6, 7, 9, and 12 for failing to comply with the written description requirement, asserting that the specification provides only a single representative species -- the polynucleotide of SEQ ID NO: 2, and fails to disclose any structure-function relationship in this species.  The Examiner had also rejected claims 3, 6, 7, 9, and 12 for failing to comply with the enablement requirement, asserting that because the specification does not teach the specific amino acids and structural motifs in the proteins encoded by the claimed polynucleotides that are essential for protein activity (specifically, malate dehydrogenase activity), the amount of experimentation required to make the claimed polynucleotides was undue.  Appellants contended that because the claims at issue recite polynucleotides having a naturally occurring polynucleotide sequence, or that encode a polypeptide having a naturally occurring amino acid sequence, "through the process of natural selection, nature will have determined the appropriate amino acid sequences [i.e., those retaining malate dehydrogenase activity]."

With regard to the written description rejection, the Board noted that "[t]he written description requirement . . . does not require a description of the complete structure of every species with a chemical genus" (Ex parte Bandman, No. 2004-2319, slip op. at 3 (B.P.A.I. January 6, 2005)).  The Board also compared the circumstances of the instant case with those faced by the Federal Circuit in Enzo Biochem, Inc. v. Gen-Probe Inc., 296 F.3d 1316 (Fed. Cir. 2002).  In Enzo Biochem, the Federal Circuit determined that an "[a]dequate written description may be present for a genus of nucleic acids based on their hybridization properties, 'if they hybridize under highly stringent conditions to known sequences because such conditions dictate that all species within the genus will be structurally similar'" (Ex parte Bandman, No. 2004-2319, slip op. at 4 (B.P.A.I. January 6, 2005) (citing Enzo Biochem, Inc., 296 F.3d at 1327)).  In the instant case, the Board determined that the genus of molecules defined by the claims was similarly limited and reversed the Examiner's written description rejection.

With regard to the enablement rejection, the Board disagreed with the Examiner's assertion that in order to satisfy this requirement, the specification must provide guidance regarding the specific amino acid residues that are tolerant to change without affecting malate dehydrogenase activity.  Instead, the Board deemed persuasive Appellants' argument that because the claims were limited to naturally occurring sequences, nature will have determined the amino acid residues that are tolerant to change (i.e., naturally occurring variants will presumably retain malate dehydrogenase activity).  In particular, in reversing the Examiner's enablement rejection, the Board determined that the Examiner had not provided sufficient evidence that a naturally occurring polypeptide that is at least 95% identical to the amino acid sequence of SEQ ID NO: 1 or a polypeptide encoded by a naturally occurring polynucleotide sequence that is at least 95% identical to the polynucleotide sequence of SEQ ID NO: 2 would not retain malate dehydrogenase activity.

Although the Board reversed both the written description and enablement rejections, it also entered a new ground of rejection for claim 12 under 35 U.S.C. § 112, second paragraph.  The Board found that the specification provided no guidance that would allow one of ordinary skill in the art to determine, with a reasonable degree of confidence, whether a polynucleotide sequence that is at least 95% identical to the polynucleotide sequence of SEQ ID NO: 2 occurs naturally.  The Board concluded that the metes and bounds of claim 12 were unclear, and therefore, that the claim was indefinite.

Ex parte Bandman (B.P.A.I. 2004)
Panel: Administrative Patent Judges Smith, Grimes, and Green
Opinion by Administrative Patent Judge Green

This article was originally published on Patently-O on June 14, 2005.

In re Fisher: EST Utility Redux

    By Donald Zuhn --

On Tuesday, the Federal Circuit will hear In re Fisher, in which the Court will address the utility requirement for the first time since the Patent Office set forth revised Utility Examination Guidelines in January 2001.  Specifically, in Fisher, the issue of patentable utility is being raised with respect to nucleic acid molecules.  In commenting on the possible importance of this case, Harold Wegner has described Fisher as having "the potential of being either the single most important pharmaceutical patent case in recent years - or a yawn."  Amicus briefs filed by such well-known biotech and pharmaceutical companies as Affymetrix, Eli Lilly, and Genentech in support of the Board's decision in Ex parte Fisher suggest that it may be the former as opposed to the latter.

The particular controversy presented in Fisher can be traced back as far as 1991, when a group of NIH investigators led by J. Craig Venter sought to protect thousands of DNA sequences corresponding to portions of expressed genes.  Venter called these gene fragments expressed sequence tags, or ESTs.  Venter's group sought to protect not only the ESTs themselves, but also the full-length sequences from which the ESTs were derived and the protein products encoded by the full-length sequences, without first determining the biological function of the encoded protein products.  In several applications filed on its ESTs, the NIH asserted a number of utilities, including the design of oligonucleotides for use in chromosomal analysis, PCR amplification, and recovering the corresponding full-length gene.  After receiving a second rejection on its initial filing, the NIH abruptly abandoned its attempts to protect the ESTs, and withdrew all of its pending EST applications from consideration.

While the withdrawal of these applications temporarily quieted the debate surrounding EST patentability, the Patent Office again stoked the fires of controversy in 1995, when it published new Utility Examination Guidelines.  The new Guidelines removed some of the obstacles to EST patenting by only requiring that an applicant assert a utility that was "specific" and "credible."  The new Guidelines had thus omitted the requirement that the assertion of utility also be "substantial," as set forth by the Supreme Court in 1966 in Brenner v. Manson.  In 1997, the Patent Office further declared that since ESTs were acknowledged to have utility apart from the full-length sequences from which they were derived, an applicant would no longer be prevented from securing protection for an EST by the failure to specify the function of the full-length sequence from which that EST was derived.

The Patent Office reversed course again in 2001 when it publishing revised Utility Examination Guidelines, reinstating the Brenner substantial utility prong.  The revised Guidelines now required that an applicant assert a specific and substantial utility for the claimed invention that would be considered credible by a person of ordinary skill in the art.  The Patent Office also issued Revised Interim Utility Guidelines Training Materials, which provided Examples indicating how the revised Guidelines were to be applied to thirteen different types of biochemical subject matter, including ESTs, as well as definitions of the three utility prongs.  In particular, the Training Materials defined "specific utility" as utility that is specific to the subject matter claimed, as contrasted with a general utility that would be applicable to the broad class of the invention; "substantial utility" as utility having a "real world" use; and "credible utility" as utility that is believable to a person of ordinary skill in the art based on the totality of evidence and reasoning provided.

In the appeal to be heard Tuesday, Appellants Dane Fisher and Raghunath Lalgudi (employees of Monsanto Co., the real party in interest) seek to reverse the Board's decision affirming the final rejection of a claim directed to five ESTs isolated from maize leaf tissue.  The five ESTs constitute only a small portion of the 4,013 sequences that Appellants originally claimed and an even smaller portion of the 32,236 sequences that Appellants disclosed in their application.  Appellants also asserted a number of utilities for the claimed ESTs in their application, including the use of the ESTs to identify polymorphisms (i.e., alternate forms, or alleles, of the claimed sequences), to design oligonucleotide probes or primers for use in isolating DNA sequences from other plants and organisms, and to measure mRNA expression levels in plant cells using microarray technology.

The Board, in Ex parte Fisher, analyzed Brenner and subsequent CCPA and CAFC decisions in In re Kirk, In re Ziegler, In re Jolles, Cross v. Iizuka, and In re Brana, and determined that "[r]ather than setting a de minimis standard, Section 101 requires a utility that is 'substantial'," or in the words of the Brenner court, "one that provides a specific benefit in currently available form."  The Board then examined Appellants' asserted utilities and determined that none of the claimed ESTs provided a specific benefit in its currently available form.  In particular, with regard to Appellants' assertion that the claimed ESTs could be used to measure mRNA expression levels in plant cells using microarray technology, the Board declared that "the asserted utility of the claimed nucleic acid - as one component of an assay for monitoring gene expression - does not satisfy the utility requirement of Section 101."

In briefing the issues before the Federal Circuit, Appellants argue that the Board erred in concluding that an EST is "subject to a heightened standard of utility . . . that hinges upon some undefined 'spectrum' of knowledge about the function of the gene that corresponds to the EST."  Appellants also contend that the Board erred in concluding that the claimed ESTs lack patentable utility "despite the undisputed existence of eight scientifically useful applications for the claimed ESTs and a commercially successful industry built upon the sale and licensing of ESTs corresponding to genes of unknown function, just like those at issue here."  In arguing against the Patent Office's application of a "heightened standard" of utility in this case, Appellants note that the Patent Office has set forth "three substantially different constructions of the utility standard over the last decade alone," and that the Board has adopted a test "so ambiguous and impracticable that even the PTO cannot articulate with any reasonable certainty when the claimed ESTs - or any other EST - might be entitled to patent protection."  Appellants also contend that the Patent Office has applied the wrong test in determining whether there is an assertion of specific utility, since "the specific utility prong only requires the existence of an identifiable benefit for the claimed invention; it does not require a benefit that is unique to the claimed invention."

The Patent Office, on the other hand, denies that Appellants' ESTs have been subjected to a heightened standard, arguing instead that Appellants merely failed to assert a specific and substantial utility for the claimed ESTs that would be considered credible by a person of ordinary skill in the art.  In its brief, the Patent Office often focuses on Appellants' failure to satisfy the specific utility prong, arguing, for example, that Appellants' asserted utilities "would apply not only to the over 32,000 ESTs Fisher discloses, and to the over 600,000 ESTs disclosed in Monsanto's [six] related appeals, but also to any ESTs derived from any organism."  In particular, the Patent Office counters Appellants' argument that because each EST only specifically binds to its complement, the specific sequence of each EST makes its use as a probe or primer specific, by stating that "there is no specific reason for using the EST to bind its complement," and therefore, "[t]o the extent that more sequence data could be acquired by using the ESTs as probes, that result would likely be true for any scrap of DNA derived from nature."  Finally, in responding to Appellants' assertion that ESTs have a real world value as part of a multi-billion dollar industry, the Patent Office contends that "batches of ESTs of unknown significance are sold for the purpose of finding targets worthy of further development, not because the individual ESTs have any specific currently available benefit."

Dr. Zuhn's article "DNA Patentability: Shutting the Door to the Utility Requirement," which was published in the summer 2001 issue of the John Marshall Law Review, contains a more thorough discussion of the history of the utility requirement, particularly with respect to DNA sequences.

This article was originally published on Patently-O on May 2, 2005.