Patent Docs

USPTO Women's Entrepreneurship Symposium

The U.S. Patent and Trademark Office will be holding the 2021 Women's Entrepreneurship Symposium on March 3, 2021, from 12:30 pm to 3:15 pm (EST).  The Symposium, which is being held as a free online event, will allow attendees to:

• Learn about navigating today's changing marketplace and the challenges and opportunities for women to succeed;
• Hear about ongoing efforts to bring more women into the innovation ecosystem; and
• Hear personal stories from senior USPTO officials and other intellectual property experts.

The Symposium will offer presentations on the following topics:

• Fireside Chat: Advancing the Role of Women in the Intellectual Property Ecosystem
• Always Dancing: Entrepreneurship and the Art of the Pivot
• Creating a Pathway to Innovation

Additional information regarding the Symposium, including an agenda and list of speakers, can be found here.  Those interested in registering for the event, can do so here.

Webinar on Claim Scope and Sufficiency

J A Kemp will be offering a webinar entitled "Claim Scope and Sufficiency: When Does a Broad Claim Fall for Insufficiency?" on March 4, 2021 from 2:30 to 3:30 pm GMT (Greenwich Mean Time).  Ravi Srinivasan and Chris Milton of J A Kemp will review the key EPO and UK cases concerning claim scope and sufficiency and further consider to what extent the recent UK Supreme Court decision in Regeneron v Kymab moves the dial in this regard.  The webinar will address the following topics:

• Review of key UK and EPO cases in this field
• Regeneron v Kymab from the UK Supreme Court -- does the legal test change?
• Recent cases applying Regeneron v Kymab

Those wishing to register can do so here.

Webinar on Protecting and Enforcing Intellectual Property Rights in Southeast Asia

The U.S. Patent and Trademark Office, in cooperation with the US-ASEAN Business Council and the U.S. Department of Commerce International Trade Administration and U.S Commercial Service, will be offering a webinar entitled "Protecting and Enforcing Intellectual Property Rights in Southeast Asia: What Small Businesses Need to Know" on March 4, 2021, from 7:00 pm to 8:45 pm (ET).  The webinar will consist of the following panel discussions:

• Panel 1: Protecting and Enforcing IP in Architecture, Engineering, and Construction (AEC) Markets
• Panel 2: Practical Market Experiences in Southeast Asia
• Panel 3: U.S. Government Resources

Additional information regarding the webinar, including an agenda and list of speakers, can be found here.  Those interested in registering for the event, can do so here.

ACI 36th Annual FDA Boot Camp

American Conference Institute (ACI) will be holding its 36th Annual FDA Boot Camp on March 24th from 8:15 am to 5:45 pm EST and March 25th from 8:30 am to 1:45 pm EST as a VIRTUAL conference.  ACI faculty will give presentations on:

• Understanding the Relevance of New FDA Initiatives and Policies and How They May Redefine the Life Sciences Industry in the Aftermath of COVID-19, by co-chairs Kurt K. Karst and Torrey Cope;
• Navigating the Approval Process for Drugs and Biologics;
• Exploring FDA's Expedited Review and Approval Programs: Applicability and Eligibility;
• Appreciating the Nuances of the Approval Process for Controlled Substances;
• Clarifying the Clinical Trial Process for Drugs and Biologics;
• Patents and Related IP Protections and Mechanisms;
• Hatch-Waxman and BPCIA Fundamentals: Understanding Follow-On Products and the Rules for Generic Entry;
• Drugs and Biologics Labeling: Appreciating the Importance of the Final Step of the Approval Process;
• Discovering the Unique Role of Current Good Manufacturing Practices ("cGMPs") in the Post Approval Process Part 1: Drug and Biologics Advertising and Promotion 101 and Part 2: Exploring the Subtleties and Safe Zones of Off-Label Communications;
• Preparing for the Worst: Adverse Events Monitoring, Pharmacovigilance, Risk Management, and Recalls; and
• Understanding the Scope of FDA Enforcement Authority and Actions.

In addition, there will be two Pre-Conference Workshops on March 23rd.  The first, entitled "FDA 101: A Guide to Agency Structure, Jurisdiction, Regulation, and Applicable Laws," which will be held from 9:00 am until noon.  The second, entitled "Medical Devices Combination Products, and Companion Diagnostics Boot Camp: A Review of FDA Guidelines and Regulations," will be held from 1:30 until 1:40 pm.  There will also be a Post-Conference Workshop on March 25th, entitled "Hatch-Waxman and BPCIA in the Trenches: Exclusivity and Bioequivalency."

An agenda for the conference and additional information regarding the workshops can be found here.  A complete brochure for this conference, including an agenda, detailed descriptions of conference sessions, list of speakers, and registration form can be obtained here.

The registration fee for the conference alone is $1,695 (paid registration by March 5th) or $1,795 for paid registration by March 23rd.  Workshop registration is $400 apiece, and there is an All-Access Pass for the conference and all three workshops for $2,095 (paid registration by March 5th) or $2,195 for paid registration by March 23rd.  Patent Docs readers are entitled to a 10% discount off of registration using discount code D10-874-874EX06.  Those interested in registering for the conference can do so here, by e-mailing CustomerService@AmericanConference.com, or by calling 1-888-224-2480.

Patent Docs is a media partner of ACI's Inaugural Summit on Women Leaders in IP Law.

DNA from Pleistocene Era Mammoth Lineages Elucidated

By Kevin E. Noonan --

The wooly mammoth (Mammuthus primigenius) is an iconic animal, like the saber tooth tiger or dire wolf, from a time in human history when our position at the top of the global food chain was decidedly not assured (and being something's prey was not limited to just other humans).  Perhaps this is a reason that resurrection of mammoths using Jurassic Park-like technology has some currency and appeal (but see How to Clone a Mammoth for reasons why this may not be such a good idea).  Perhaps paradoxically, the mammoth arose in Africa 5 million years ago and like its (very) distant Homo sapiens relatives migrated to colonize the Northern Hemisphere, with most of the evolutionary adaptations to new habitats (and speciation that accompanied them) rising in the Pleistocene Era (from about 2.6 million to 12 years ago).  From these speciation events arose the Columbian mammoth in North America about 1.5 million years ago and the "classic" wooly mammoth in northeastern Siberia about 700,000 years ago.

Recently an international team* elucidated some genetic relationships between mammoths using DNA extracted from specimens from the Early and Middle Pleistocene, in a paper entitled "Million-year-old DNA sheds light on the genomic history of mammoths," in the journal Nature.  These results, termed "deep-time paleogenomics" by the authors, were obtained from three specimens, two of which were more than 1 million years old.  The specimens represented two distinct lineages present in Eastern Siberia in early Pleistocene, one of which resulted in wooly mammoth populations that survived to become contemporaneous with humans.  The third lineage gave rise to first mammoths in North America (Mammuthus columbi), resulting from a hybrid between these two lineages in Siberia in the Middle Pleistocene.  And perhaps not surprisingly, these researchers found most of the adaptation to cold seen in these animals were present in the samples from one million years ago.

As reported by these researchers, DNA was extracted from the three specimens using now established techniques for highly degraded DNA samples and libraries prepared.  The libraries were sequenced and these sequences compared to genomic DNA sequences from the African savannah elephant (Loxodonta africana) and mitochondrial DNA from the Asian elephant (Elephas maximus).  Perhaps not unexpectedly, the specimen DNA was "considerably more fragmented and had higher levels of cytosine deamination than DNA from permafrost-preserved samples dating to the Late Pleistocene subepoch," which required modifications to the sequence analysis protocols.  Nevertheless, these researchers reported that they obtained complete mitochondrial DNA genomes from the three samples and 49 million (from the oldest sample, named Krestovka), 884 million (the Adycha sample)  and 3,671 million base pairs (the Chukochya sample) of nuclear genomic data from the three samples (with the highest DNA recovery coming from the most recent specimen, which from tooth morphology they thought to be an early wooly mammoth specimen).

The ages of these specimens were then determined using the mitochondrial DNA sequences, ranging from 1.65 Ma (2.08–1.25 Ma; Krestovka), 1.34 Ma (1.69–1.06 Ma; Adycha) and 0.87 Ma (1.07–0.68 Ma; Chukochya). Genomic DNA was used to verify the two specimens having the highest amount of gDNA sequence obtained, against estimates of the highest number of changes from the latest Africa savannah element ancestor, which yielded 1.28 Ma (1.64–0.92 Ma) and 0.62 Ma (1.00–0.24 Ma), respectively.  These results were similar to the dates derived from the generally more intact mitochondrial DNA, but the authors cautioned that "this analysis is based on low-coverage data and the confidence intervals are wide."  Nevertheless, the authors also note that "[t]he DNA-based age estimates for the [the two genomic DNA] specimens are consistent with the geological age inferences that were independently derived from biostratigraphy and palaeomagnetism."

The genetic analyses indicated that the samples were divergent from known mammoth species from the Late Pleistocene, and were consistent with the younger two specimens (Adycha and Chukochya) being ancestral to the wooly mammoths, while the oldest specimen (Krestovka) apparently diverged prior to the species split between the wooly mammoth and the Columbian (North American) mammoths.  The oldest specimen was estimated by these authors to have split from the later mammoth lineages between 2.66 and 1.78 million years ago based on both mitochondrial and genomic DNA data and had fewer derived alleles that differed from the Asian elephant than the younger two (indicating a closer evolutionary relationship).  Due to the relative closeness in time for the eldest and one of the younger specimens, these results are consistent with these two lineages together inhabiting eastern Siberia in the Early Pleistocene, with the earliest having diverged from all later mammoth species before mammoths appeared in North America.

Regarding the Columbian (North American) mammoth, the genetic analyses also indicated that these mammoths shared a higher proportion of it ancestry from the earlier-diverging Krestovka species, which showed "excess derived allele-sharing between the Columbian mammoth and the Krestovka specimen."  These statistics were further consistent with one migration of n admixture of mammoth populations of the species from the Krestovka specimen (38-43% ancestry) and the wooly mammoth (57-62% ancestry).  Further analysis of later Columbian mammoth specimens indicated a second admixture with North American wooly mammoth species.

The researchers then assessed the genetic adaptations expected to be found in animals descendent from African elephants living in Siberia, notably cold-tolerance and open-habitat adaptations.  These analyses were performed using protein-coding portions of the genetic information derived from these samples in comparison with known adaptations from Late Pleistocene wooly mammoths (as further compared with African and Asian elephants, who carried the "ancestral" alleles).  As reported in the paper, "85.2% (782 out of 918) and 88.7% (2,578 out of 2,906) of the mammoth-specific protein-coding changes were already present in the genomes of Adycha . . . and Chukochya [specimens], respectively."  These specimens showed no specific genetic changes arising in these populations in response to known changes in climate and mammoth morphology arising in the Middle Pleistocene.  These researchers also interrogated the DNA samples for 91 changes known to have arisen in the mammoth lineage.  These included genes thought to be involved in "hair growth, circadian rhythm, thermal sensation and white and brown fat deposits," the researchers finding "the vast majority of coding changes were present in both the Adycha (87%) and Chukochya (89%) genomes."  In contrast, another gene ("TRPV3, which encodes a temperature-sensitive transient receptor channel that is potentially involved in thermal sensation and hair growth") possessed only 2 of 4 amino acid sequence changes found in Late Pleistocene wooly mammoths, which indicated to these authors that these genetic alterations "occurred over several hundreds of thousands of years, rather than during a single brief burst of adaptive evolution."

The authors conclude by a discussion of their results suggesting an admixture of an earlier-arising mammoth ancestor with wooly mammoths to produce the Columbian (North American) mammoth through a "hybrid speciation event" resulting in an almost 50:50 mix of ancestor species DNA.  Mitochondrial DNA assessments suggested that the most recent common female ancestor of all Late Pleistocene Columbian mammoths lived about 420 thousand years ago, which these authors use as a minimum date for the admixture event.  Because it is known that mammoths existed in North America 1.5 million years ago, these authors posit initial North American colonization by the Krestovka ancestral species.  They conclude their report by stating:

The retrieval of DNA that is more than one million years old confirms previous theoretical predictions that the ancient genetic record can be extended beyond what has been previously shown.  We anticipate that the additional recovery and analysis of Early and Middle Pleistocene genomes will further improve our understanding of the complex nature of evolutionary change and speciation.  Our results highlight the value of perennially frozen environments for extending the temporal limits of DNA recovery, and hint at a future deep-time chapter of ancient DNA research in which specimens from high latitudes will have an important role.

* From Centre for Palaeogenetics, Stockholm, Sweden; Department of Bioinformatics and Genetics, Swedish Museum of Natural History, Stockholm, Sweden; Department of Cell and Molecular Biology, National Bioinformatics Infrastructure Sweden, Science for Life Laboratory, Uppsala University, Uppsala, Sweden; Department of Zoology, Stockholm University, Stockholm, Sweden; Section for Computational and RNA Biology, Department of Biology, University of Copenhagen, Copenhagen, Denmark; The Francis Crick Institute, London, UK; Department of Biomolecular Engineering, University of California Santa Cruz, Santa Cruz, CA; Institute for Biochemistry and Biology, University of Potsdam, Potsdam, Germany; Department of Biological Sciences, Middle East Technical University, Ankara, Turkey; Department of Earth Sciences, Natural History Museum, London, UK; College of Plant Protection, China Agricultural University, Beijing, China; The Arctic University Museum of Norway, UiT – The Arctic University of Norway, Tromsø, Norway; Geological Institute, Russian Academy of Sciences, Moscow, Russia; Department of Ecology and Evolutionary Biology, University of California Santa Cruz, Santa Cruz, CA; Howard Hughes Medical Institute, University of California Santa Cruz, Santa Cruz, CA; and Department of Archaeology and Classical Studies, Stockholm University, Stockholm, Sweden.

Image of Woolly mammoth model Royal BC Museum in Victoria by Thomas Quine, from the Wikimedia Commons under the Creative Commons Attribution 2.0 Generic license.

Infinity Computer Products, Inc. v. Oki Data Americas, Inc. (Fed. Cir. 2021)

By Michael Borella --

Infinity Computer Products ("Infinity") sued Oki Data in the District of Delaware for infringement of four patents.  The District Court found the patents invalid due to indefiniteness and the Federal Circuit affirmed.  This case serves to illustrate two important points in patent law: (i) taking contradictory positions during prosecution will be held against the applicant, and (ii) the Federal Circuit will take said contradictory positions to an unnecessary extreme in order to support a holding of indefiniteness.

Representative of the Infinity patents is U.S. Patent No. 6,894,811, claim 1 of which recites:

A method of creating a scanning capability from a facsimile machine to a computer, with scanned image digital data signals transmitted through a bi-directional direct connection via a passive link between the facsimile machine and the computer, comprising the steps of:
    by-passing or isolating the facsimile machine and the computer from the public network telephone line;
    coupling the facsimile machine to the computer;
    conditioning the computer to receive digital facsimile signals representing data on a scanned document; and
    conditioning the facsimile machine to transmit digital signals representing data on a scanned document to the computer, said computer being equipped with unmodified standard protocol send/receive driver communications software enabling the reception of scanned image signals from the facsimile machine, said transmitted digital facsimile signals being received directly into the computer through the bi-directional direct connection via the passive link, thereafter, said computer processing the received digital facsimile signals of the scanned document as needed.

The '811 patent is a continuation in part of U.S. Patent No. 5,530,558.  The emphasized term "passive link" was a point of contention in the suit and ultimately led to the invalidation of all of the Infinity patents.

The claimed invention is directed to "using a fax machine as a printer or scanner for a personal computer."  According to the specification, its goal is to "provide a circuit for interfacing a PC and a facsimile to enable the facsimile to be utilized as a scanner or a printer for a PC and to accomplish all of the objectives of a scanner or a printer."

Various embodiments involve this circuit being internal or external to a PC.  The internal version, with the circuit integrated into a fax modem, is illustrated in Figure 2b of the '811 patent, reproduced below.

An alternative embodiment involves the fax modem and circuit being integrated into the fax machine, and the PC connected to the fax machine by way of an RS232 serial cable.  This is illustrated in Figure 2f of the '811 patent, also reproduced below.  The parent '558 patent does not include Figure 2f.

During initial prosecution, the examiner cited U.S. Patent No. 5,452,106 ("Perkins") against the claims as anticipatory art.  Perkins discloses a similar arrangement in which a PC uses a fax machine as a printer and scanner.

After a series of amendments, Infinity achieved an allowance by amending the claims as shown above.  This involved introducing the aforementioned term "passive link".  Notably, this term does not appear in the '811 patent nor does it appear in the parent '558 patent.  Nonetheless, Infinity relied heavily on this term and argued:

The Applicant creates a passive link between the facsimile machine and the computer in order to accommodate the signal transfer for printing or scanning.  Therefore, the Applicant does not require any intervening apparatus as does Perkins.  The applicant therefore believes Perkins did not anticipate the methods used by the Applicant.

Perkins' device 3 or card design requires a modem to be integrated into it in order to transfer signals for scanning or printing as part of his computer and facsimile transceiver interface.  In contrast, the Applicant can transfer digital signals between the facsimile transceiver and the computer without the need for a modem at the computer interface.

In making this argument, Infinity relied on the disclosure of Figure 2f, that did not have a modem between the fax machine and the PC.  Infinity stated that:

Contrary to the above, when the Applicant transfers digital data from the facsimile transceiver through a passive link for scanning to the computer, the non-intercepted data enters through the RS 232 type connector port of the computer and passes directly to the I/O Bus and is processed by the receiving circuits (i.e., UART, CPU) of the computer, providing a true non intercepted digital signal between the facsimile transceiver and the computer.

In effect, the Applicant's method does not use intermediary peripheral circuitry for signal interception, resulting in demodulation or modulation which is required by Perkins with his card or device 3.

Thus, Infinity's claims should have been narrowed by prosecution history estoppel to the embodiment of Figure 2f, or to at least exclude the embodiment of Figure 2b which does not have an RS 232 line and instead uses a modem between the fax machine and PC.

After issuance, the '811 patent was subject of three ex parte re-examinations.  In one, U.S. Patent No. 5,900,947 ("Kenmochi") was cited against the claims.  To antedate this reference, Infinity argued that claim 1 should be given the earlier effective filing date of the '558 parent.  But as noted above, the '558 patent does not include Figure 2f (recall that that '811 patent is a continuation in part).

In arguments, Infinity changed its tune and stated that "the RJ-11 telephone cable shown in Figs. 2b, 2c and 2d of the ['278 application] is the 'direct' and 'passive link.'"  This is problematic, because Infinity's previous arguments over Perkins effectively required the claims to be limited to the embodiment of Figure 2f, and also because Perkins arguably read on the embodiments of the '811 patent containing the RJ-11 cable.  Nonetheless, the re-examination resulted in another allowance.

In the District Court, Oki Data contended that Infinity took two conflicting positions during prosecution, one to overcome Perkins and the other to overcome Kenmochi.  According to the Oki Data, this created uncertainty "as to where the 'passive link' ends and where the 'computer' begins".  The District Court agreed, finding that "Infinity had taken materially inconsistent positions regarding the extent of the claimed "passive link"—specifically, whether it ends at the I/O bus inside the computer (as argued to distinguish Perkins) or merely at the computer's port (as argued to antedate Kenmochi)."  This rendered the claims indefinite.

On Appeal, the Federal Circuit agreed.  First, the Court noted that "a patent is invalid for indefiniteness if its claims, read in light of the specification delineating the patent, and the prosecution history, fail to inform, with reasonable certainty, those skilled in the art about the scope of the invention."  Of particular relevance is the principle that "[i]ndefiniteness may result from inconsistent prosecution history statements where the claim language and specification" otherwise do not afford the claims definiteness.

The facts on record, as described above, probably should have been sufficient to affirm the District Court.  But the Federal Circuit went further, stating that Infinity's arguments to overcome Perkins "would lead one of ordinary skill to believe a passive link does not end at the computer's port but rather reaches to the I/O bus of the computer."  Thus, the Court found both the claimed "passive link" and "computer" to be indefinite.

This appears to be a stretch, however.  Based on Figure 2f, one of ordinary skill in the art would understand that an RS 232 link is serial and would terminate at an RS 232 port.  Such a skilled person would also understand that the typical I/O bus is parallel.  Therefore, behind this port would be circuitry to serialize / de-serialize the bits transported by the link to a parallel format supported by the I/O bus.

The notion that the passive link would somehow extend to the I/O bus was not supported by the state of the art nor was it actually argued by Infinity.  Instead, Infinity wrote that "the non-intercepted data enters through the RS 232 type connector port of the computer and passes directly to the I/O Bus and is processed by the receiving circuits (i.e., UART, CPU) of the computer."  The language here about the UART circuit (which processes serialized communications) is somewhat confusing but should not override the more logical conclusion that the passive link is coextensive with the RS 232 cable.

The Court seems to recognize that it is wandering into Kafkaesque territory, and noted that "[w]e recognize that, in a vacuum, it might seem odd to hold 'computer' indefinite."  But the Court justified the outcome by shifting the blame to Infinity's own unclear statements.

In short, the outcome for this case appears to be correct.  Infinity took contradictory positions during prosecution, which is enough to render the claims indefinite.  The whole discussion of the boundary between the passive link and the computer being uncertain was superfluous at best and specious at worst.

Infinity Computer Products, Inc. v. Oki Data Americas, Inc. (Fed. Cir. 2021)
Panel: Chief Judge Prost and Circuit Judges Clevenger and Taranto
Opinion by Chief Judge Prost

Amgen Inc. v. Sanofi (Fed. Cir. 2021)

By Kevin E. Noonan --

A little less than four years ago, the Federal Circuit rendered a decision in Amgen Inc. v. Sanofi that brought clarity to how the Court (and U.S. Patent and Trademark Office) should apply the written description requirement in 35 U.S.C. § 112(a) to properly circumscribe the scope of claims to monoclonal antibodies.  Earlier this month, on an appeal from remand, the Court took aim at the enablement requirement for antibody claims, with similar, scope-limiting results.

The case arose when Amgen sued Sanofi and Regeneron over sales of Praluent® (alirocumab), which allegedly competes with Amgen's Repatha™ (evolocumab); Amgen's asserted patents, U.S. Patent Nos. 8,829,165 ("'165 patent") and 8,859,741 ("'741 patent"), claim a genus of antibodies that encompass Praluent®.  As background, blood plasma contains low-density lipoproteins that bind cholesterol and are associated with atherosclerotic plaque formation.  Liver cells express receptors for LDL (LDL-R) wherein binding thereto reduces the amount of LDL cholesterol in blood and reduces the risk of plaque formation and cardiovascular disease.  PCSK9 (proprotein convertase subtilisin kexin type 9) is a molecule that binds to and causes liver cell LDL-R to be destroyed, thus reducing the capacity and effectiveness of the liver cell's ability to reduce serum LDL-cholesterol.  The antibodies at issue in this suit bind to PCSK9 and prevent PCSK9 from binding to LDL-R, preventing their destruction and resulting in lower serum cholesterol.

The following claims were recited in the opinion as being relevant to the issues before the Court:

Claims of the '165 patent:

1.  An isolated monoclonal antibody, wherein, when bound to PCSK9, the monoclonal antibody binds to at least one of the following residues: S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of SEQ ID NO:3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDL[-]R.

19.  The isolated monoclonal antibody of claim 1 wherein the isolated monoclonal antibody binds to at least two of the following residues S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of PCSK9 listed in SEQ ID NO:3.

29.  A pharmaceutical composition comprising an isolated monoclonal antibody, wherein the isolated monoclonal antibody binds to at least two of the following residues S153, I154, P155, R194, D238, A239, I369, S372, D374, C375, T377, C378, F379, V380, or S381 of PCSK9 listed in SEQ ID NO: 3 and blocks the binding of PCSK9 to LDLR by at least 80%.

Claims of the '165 patent:

1.  An isolated monoclonal antibody that binds to PCSK9, wherein the isolated monoclonal antibody binds an epitope on PCSK9 comprising at least one of residues 237 or 238 of SEQ ID NO: 3, and wherein the monoclonal antibody blocks binding of PCSK9 to LDLR.

2.  The isolated monoclonal antibody of claim 1, wherein the isolated monoclonal antibody is a neutralizing antibody.

7.  The isolated monoclonal antibody of claim 2, wherein the epitope is a functional epitope.

It is important to note that, while reciting the structure of the residues on PCSK9 (the antigen) that are bound by the claimed antibody, the claim does not recite any structural limitations of the antibody.  The only antibody characteristics recited as limitation are functional, i.e., the ability to bind (and not even specifically bind) to at least one of the recited PCSK9 residues and block PCSK9's interaction with the LDL-R.

Evidence at the first trial showed that Amgen had produced a plurality of anti-PCSK9 antibodies and screened them for the ability to inhibit PCSK9 binding to LDL-R.  This screening was done using a "trial and error" process that reduced 3,000 human monoclonal antibodies down to 85 antibodies that "blocked interaction between the PCSK9 . . . and the LDLR [at] greater than 90%," of which the specification illustrated the three-dimensional binding arrangement for two (one of which became the Repatha™ antibody) by x-ray crystallography.  The specification of the Amgen patents in suit disclose amino acid sequence information for twenty-two human anti-PCSK9 antibodies able to compete for PCSK9 binding with these two more fully characterized antibodies.  Regeneron's patents (not at issue here) recited antibody-specific amino acid sequences for its claimed anti-PCSK9 antibodies.

The jury in the earlier case found Amgen's patents not to be invalid.  The District Court had excluded evidence relating to written description and enablement based on Praluent® and other post-priority-date antibodies (i.e., that were produced after Amgen's earliest priority date).  The District Court, relying on Noelle v. Lederman as precedent, instructed the jury that an applicant can be entitled to claim scope encompassing generically described antibodies (as was the case for Amgen's claims) provided that the applicant provided a full characterized, novel antigen.

The Federal Circuit reversed in part, affirmed in part, vacated in part, and remanded, in an opinion by Chief Judge Prost, joined by Judges Taranto and Hughes.  With regard to the written description question, the Court vacated and remanded, on the grounds that the District Court had instructed the jury based on the Court's pre-Ariad Noelle v. Lederman precedent, which was inconsistent with the Court's later en banc decision in Ariad v. Eli Lilly & Co.  The Court also found it to be error for the District Court to have excluded evidence regarding enablement, related to the "lengthy and potentially undue experimentation" Amgen needed to employ to arrive at its antibodies that fell within the scope of the claims of the '165 and '741 patents.  The Federal Circuit ordered a new trial for the District Court to consider post-priority-date evidence for the purposes of both enablement.  The District Court remanded for a new trial on written description as well, based on the jury instruction and evidentiary errors.

On remand, the jury found that claim 7 of the '741 patent and claims 19 and 29 of the '165 patent were not invalid.  The District Court granted Sanofi's motion for JMOL with regard to enablement for these claims but denied JMOL on written description.  This appeal followed.

In the instant appeal, the Federal Circuit affirmed in an opinion by Judge Lourie, joined by Chief Judge Prost and Judge Hughes.  The panel grasps the nettle of the question before it immediately, stating that "[t]he claimed antibodies are defined by their function: binding to a combinations of sites (residues) on the PCSK9 protein, in a range from one residue to all of them; and blocking the PCSK9/LDLR interaction."  This aspect of the issue before the Court was just as important and dispositive for the enablement question as it has become for the question of written description, under the reasoning set forth in this opinion.  The panel reverted (as it must) to its decision in In re Wands (and its famous "Wands factors"), the dispositive factor in the Court's decision being the amount of experimentation required to encompass the full scope of the claims at issue.  Albeit being a question of law, enablement depends particularly on the facts from which conclusions of law are based.  The opinion is sensitive to the requirement for patenting that the specification enable practice of the claimed invention throughout its full scope, and with the Wands rubrics that the scope of the claims can determine the extent of experimentation required and whether such experimentation is undue.  The opinion then focused on claims 19 and 29 of the '165 patent and claim 7 of the '741 patent in rendering its decision.

Amgen's arguments were grounded in the disclosure in the specification regarding the type of experimentation required and the guidance provided therein on the extent of such experimentation, while Defendants argued that the scope of these claims encompassed "millions of antibody candidates," that antibody production was unpredictable, and that the specification lacked sufficient guidance because, inter alia, "practicing the full scope of the claims requires substantial trial and error."  Defendants emphasized not the antibodies Amgen had actually made but "the number of candidates that must be made and tested to determine whether they satisfy the claimed function."

Calling In re Wands the Court's "go to" precedent, the opinion states that while itself a monoclonal antibody case, "Wands did not proclaim that all broad claims to antibodies are necessarily enabled" because "[f]acts control."  Here, the panel considered the facts (and the findings of invalidity) in more recent cases, including Wyeth & Cordis Corp. v. Abbott Laboratories, Enzo Life Sciences, Inc. v. Roche Molecular Systems, Inc., and Idenix Pharmaceuticals LLC v. Gilead Sciences Inc.  In all these cases, of course, the Federal Circuit found that the claims were not enabled, due to the broad scope of embodiments the claims in these cases encompassed and the amount of undue experimentation required to satisfy the enablement requirement throughout its full scope.  The panel set forth its synthesis of the Federal Circuit's analysis regarding satisfaction of the enablement requirement arising from these cases:

What emerges from our case law is that the enablement inquiry for claims that include functional requirements can be particularly focused on the breadth of those requirements, especially where predictability and guidance fall short.  In particular, it is important to consider the quantity of experimentation that would be required to make and use, not only the limited number of embodiments that the patent discloses, but also the full scope of the claim.

And citing a footnote in McRO, Inc. v. Bandai Namco Games Am. Inc.:

In cases involving claims that state certain structural requirements and also require performance of some function (e.g., efficacy for a certain purpose), we have explained that undue experimentation can include undue experimentation in identifying, from among the many concretely identified compounds that meet the structural requirements, the compounds that satisfy the functional requirement [emphasis added].

This precedent was controlling here:  "[w]hile functional claim limitations are not necessarily precluded in claims that meet the enablement requirement, such limitations pose high hurdles in fulfilling the enablement requirement for claims with broad functional language."  As applied to Amgen's claims, the panel recognized each of them to be "a composition claim defined, not by structure but by meeting functional limitations."  This outcome is consistent with Wands, according to the opinion, because the "functional breadth" of these claims is "indisputably broad" and "the claims are far broader in functional diversity than the disclosed examples."  Taking a real property analogy from AbbVie Deutschland GmbH & Co. v. Janssen Biotech, Inc., the opinion states that "[i]f the genus is analogized to a plot of land, the disclosed species and guidance 'only abide in a corner of the genus.'"  The opinion also referenced the unpredictability of the antibody arts as a relevant (and supportive) Wands factor in favor of invalidity.  And the quantum of guidance factor from Wands was also deficient, according to the opinion, because "any reasonable factfinder would conclude that the patent does not provide significant guidance or direction to a person of ordinary skill in the art for the full scope of the claims."

Importantly, the panel cabined its decision by stating that while the "substantial amount of time and effort" required to produce the scope of antibodies claimed here is undue, "[w]e do not hold that the effort required to exhaust a genus is dispositive" (emphasis in opinion).  The Court struck a balance:  "[t]he functional limitations here are broad, the disclosed examples and guidance are narrow, and no reasonable jury could conclude under these facts that anything but 'substantial time and effort' would be required to reach the full scope of claimed embodiments."  But the facts here (which distinguish this decision from Wands) are that "the evidence showed that the scope of the claims encompasses millions of candidates claimed with respect to multiple specific functions, and that it would be necessary to first generate and then screen each candidate antibody to determine whether it meets the double-function claim limitations."  Under these facts, the substantialness of such time and effort was sufficient to be considered undue experimentation by the Court.

While providing yet another fact-bound basis for invalidating (or limiting the scope of) claims to biotechnological inventions, it is unlikely to have been a coincidence that the opinion is authored by Judge Lourie, the architect of the Court's emphasis on structure in applying the written description requirement to biotechnology claims.  As the Judge emphasized in his seminal Regents of the University of California v. Eli Lilly case:

Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention," citing Lockwood v. American Airlines, Inc. (Fed. Cir. 1997).

An adequate written description of a DNA, such as the cDNA of the recombinant plasmids and microorganisms of the '525 patent, "requires a precise definition, such as by structure, formula, chemical name, or physical properties," not a mere wish or plan for obtaining the claimed chemical invention.  Fiers v. Revel (Fed.Cir.1993).  Accordingly, "an adequate written description of a DNA requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it;  what is required is a description of the DNA itself."  Id.

A written description of an invention involving a chemical genus, like a description of a chemical species, "requires a precise definition, such as by structure, formula, [or] chemical name," of the claimed subject matter sufficient to distinguish it from other materials.  Fiers;  In re Smythe ("In other cases, particularly but not necessarily, chemical cases, where there is unpredictability in performance of certain species or subcombinations other than those specifically enumerated, one skilled in the art may be found not to have been placed in possession of a genus․").

This precedent is thus well grounded in the Federal Circuit's concern that a patentee must satisfy the quid pro quo of the patent grant, so that the specification supports its claims throughout their entire scope, whether on enablement or written description grounds.  It has been a bane for the biotechnology industry that the courts (and to a lesser extent, Congress) have played "catchup" in determining the proper application of these standards to biotechnology inventions, resulting in claims either invalidated under such changing standards or failing to encompass the activities of accused infringers.  But this decision provides a consistent standard ("structure, structure, structure," as recited by former Chief Judge Rader on several occasions) and one that can be applied with consistency even though the resulting scope may prove insufficient to provide enough support to justify the costs of commercialization.  Which will be a bane on everyone.

Amgen Inc. v. Sanofi (Fed. Cir. 2021)
Panel: Chief Judge Prost and Circuit Judges Lourie and Hughes
Opinion by Circuit Judge Lourie