Patent Docs

Webinar on Prosecuting Patents for Sales and Licensing

The American Bar Association (ABA) Center for Professional Development, Section of Intellectual Property Law, and Young Lawyers Division will be offering a live webinar entitled "Prosecuting Patents for Sales and Licensing" on May 26, 2015 from 1:00 to 2:30 pm (ET).  Alexander Franco (moderator) of Patent GC; Christopher K. Agrawal of Bookoff McAndrews, PLLC; and Sabrina Chang, Patent Director of Brokerage Services, Epicenter IP Group will give a brief overview of today’s patent brokerage and licensing markets, along with basic valuation principles and metrics to show which aspects of patents are most sought after or avoided.  The panel will also identify strategies for both drafting applications and prosecuting patent applications to maximize marketability of patent assets, both individually and collectively as a portfolio, and identify attack plans for positioning both small and large portfolios for sale, including how best to utilize the seller's potentially scarce resources before a sale.

The registration fee for the webcast is $150 for members, $95 for sponsor members, and $195 for the general public.  Those interested in registering for the webinar, can do so here.

Patent Profile: DermTech Receives Patent for Method of Detecting Melanoma in Human Subjects

By Josh Bosman --

The U.S. Patent and Trademark Office recently issued a notice of allowance for U.S. Application No. 14/199,900, which is entitled "Diagnosis of Solar Lentigo by Nucleic Acid Analysis."  The '900 application, which is assigned to the DermTech International, contains claims to a method of detecting melanoma in a human subject.  DermTech is a San Diego-based biotechnology company developing and commercializing gene expression tests to facilitate the diagnosis of dermatologic conditions.

Melanoma is the most serious type of skin cancer, but can be treated successfully if it is detected early.  Most melanoma deaths can be prevented by surgical excision if they are detected in their early stages.  The methods of the '900 application help to enable physicians to determine the nature and extent of suspicious lesions of the skin by providing accurate, objective information to the physicians to improve care while reducing costs.  More specifically, DermTech's technology allows the analysis of skin samples collected non-invasively using an adhesive patch.

The '900 application has two independent claims which recite:

Claim 1.    A method of detecting melanoma in a human subject comprising:
    (a) obtaining a sample of a skin lesion suspected of comprising melanoma from a human subject, wherein the skin lesion sample comprises or is suspected of comprising a nucleic acid molecule expressed from C6orf218;
    (b) detecting the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample, whereby the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample in an amount that is greater than the presence of C6orf218 in a non-melanoma sample is indicative of melanoma in the skin lesion sample, wherein detecting the presence of a nucleic acid molecule expressed from C6orf218 is by application of a detectably labeled probe that hybridizes to a nucleic acid molecule expressed from C6orf218; and
    (c) characterizing the skin lesion as having melanoma or not having.

Claim 15.    A method for diagnosing melanoma in a subject, comprising:
    (a) obtaining a sample of a skin lesion suspected of comprising melanoma from a subject, wherein the skin lesion sample comprises or is suspected of comprising a nucleic acid molecule expressed from C6orf218;
    (b) detecting the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample, wherein detecting the presence of a nucleic acid molecule expressed fromC6orf218 is by application of a detectably labeled probe that hybridizes to a nucleic acid molecule expressed from C6orf218; and
    (c) comparing the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample to the presence of C6orf218 in a non-melanoma sample, whereby the increased presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample as compared to the non-melanoma sample is indicative of melanoma, thereby diagnosing the skin lesion as having melanoma.

A review of the file history of the `900 application (examined under Track I) indicates a rejection under 35 U.S.C. § 101 was issued (along with rejections under §§ 112, 102, and 103) in the first Office Action, mailed December 10, 2014.  The Action stated that the claimed invention was directed to patent ineligible subject matter.  Specifically, the Action asserted that the claims were directed to a natural correlation or a natural principle (i.e., the claims reflect the natural correspondence between gene expression and melanoma).  Furthermore, the Action asserted that the claimed methods failed to incorporate steps that amount to significantly more than the natural principles themselves because the steps merely incorporate conventional, routine techniques while failing to incorporate some other inventive concept.

In response, with respect to the 101 rejection, the Applicant argued that the claims, as amended, are patent eligible because the amended claims do not seek to tie up the use of C6orf218, and others are not excluded from using C6orf218 or C6orf218 expression products in other ways that do not utilize the claimed methods for detecting or diagnosing melanoma.  Furthermore, the Applicant argued that the claims as amended are not directed to a judicial exception because the claims are directed to methods of using "a detectably labeled probe that hybridizes to a nucleic acid molecule expressed from C6orf218" and to determine the presence of C6orf218 for "detecting melanoma in a human subject" or for "diagnosing melanoma in a subject".

Finally, the Applicant argued that the amended claims recite an inventive concept because claims 1 and 15, provide methods for "detecting melanoma in a human subject" or for "diagnosing melanoma in a subject," by "detecting the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample," which, according to the Applicant, is not taught, alone or in combination, by the art cited in the Action.

Claims 1 and 15 as amended recited:

Claim 1.    A method of detecting distinguishing melanoma from dysplastic nevi or normal pigmented skin in a human subject comprising:
    (a) obtaining a sample of a skin lesion suspected of comprising melanoma from a human subject, wherein the skin lesion sample comprises or is suspected of comprising a nucleic acid molecule expressed from C6orf218;
    (b) detecting the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample, whereby the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample in an amount that is greater than the presence of C6orf218 in a non-melanoma sample is indicative of melanoma in the skin lesion sample, wherein detecting the presence of a nucleic acid molecule expressed from C6orf218 is by application of a detectably labeled probe that hybridizes to a nucleic acid molecule expressed from C6orf218analyzing expression of a nucleic acid molecule encoded by C6orf218; and
    (c) characterizing the skin lesion as having being melanoma or not having ,dysplastic nevi, or normal pigmented skin, thereby distinguishing melanoma from dysplastic nevi or normal pigmented skin in a human subject.

Claim 15.    A method for diagnosing melanoma in a subject, comprising:
    (a) obtaining a sample of a skin lesion suspected of comprising melanoma from a subject, wherein the skin lesion sample comprises or is suspected of comprising a nucleic acid molecule expressed from C6orf218;
    (b) detecting the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample, wherein detecting the presence of a nucleic acid molecule expressed fromC6orf218 is by application of a detectably labeled probe that hybridizes to a nucleic acid molecule expressed from C6orf218; and
    (c) comparing the presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample to the presence of C6orf218 in a non-melanoma sample, whereby the increased presence of a nucleic acid molecule expressed from C6orf218 in the skin lesion sample as compared to the non-melanoma sample is indicative of melanoma, thereby diagnosising the skin lesion as having melanoma providing a gene expression profile of a target area suspected of being melanoma on the skin of the subject; and
(b) analyzing the subject's gene expression profile with respect to a reference gene expression profile obtained from a corresponding normal skin sample, wherein the reference gene expression profile comprises an expression value of a target gene that is C6orf218.

The file history indicates that a search was performed by the Examiner following the Applicant's response, but the notice of allowance mailed on March 30, 2015 provides no additional comments concerning the allowability of the claims other than noting that the application is in condition for allowance.

Final "Ministerial" Rule Amendments for Practice Before the PTAB

By Andrew Williams --

On May 19, 2015, the U.S. Patent and Trademark Office published its first "Final Rules" package of amendments to the Rule of Practice before the Patent Trial and Appeal Board ("PTAB").  Keeping with Director Lee's announcement on March 27, 2015 (see "USPTO Director Announces "Quick-Fix" and Anticipated Changes to PTAB Practice"), this set of rules was described as including more ministerial changes.  The Office promised a second set of rules that will address more "involved" changes to the rules.  These rules changes stemmed from a "nationwide listening tour" last year, which culminated in a request last June for public feedback about the AIA post-grant proceedings.  This request was in the form of seventeen questions.  According to the current Final Rules, thirty-seven comments were submitted from individuals, corporations, bar associations, and law firms.  The Office promised to address all of these comments that do not involve changes to page limitations in the second rule package later this year.  Please find below the changes made in the current rules package:

Patent Owner's Motion to Amend

In perhaps the most significant change of the current rules package, the Patent Office is increasing the page limit for Motions to Amend by ten pages (to a total of twenty-five pages), and removing the necessity of including the claim listing within this limit.  Instead, the claim listing can now be provided in an appendix.  In order to keep things equivalent, the Office also increased by a commensurate amount the number of pages for an opposition to the motion to amend.  The Office had received a wide range of suggestions to deal with this issue, including creating a flexible page limit based on the number of substitute claims, or allowing the patent owner to allocate any unused pages from the Patent Owner's Response.  However, these suggestions would have been difficult to administer.

Petitioner's Reply

This Office is also increasing the page limit for the Petitioner's reply brief from fifteen pages to twenty five.  The problem was that fifteen page was believed to not be commensurate with the Patent Owner's response.  This was especially problematic for the petitioner when the Patent Owner raised new issues in the response.  One suggestion was to increase the number of pages by a flexible amount, to be set by the amount of space addressing new issues.  However, this too would have been difficult to administer.

Required Font

The new rules will require the use of 14-point Times New Roman proportional font, with normal spacing.  Originally, the Office only required a proportional or monospaced font, 14-point or larger (with the additional requirement that monospaced font not contain more than ten characters per inch.  However, because parties have used overly narrow fonts that met the letter of the rule, but proved difficult to read, the Board is now going to require uniformity in font type to ensure readability.

Counsel

The Office is clarifying that more than one back-up counsel can be designated.  This will be accomplished with an amendment to 37 C.F.R. § 42.10(a), changing "a" to "at least one."

Fees

The Office is requiring that fees due under 37 C.F.R. § 42.15 be based on not only the number challenged claims, but also on the claims from which they depend (unless already included).  The reason given was that, in order to understand the scope of a dependent claim, it is necessary to also construe the claims from which it depends.

Oppositions and Replies and Page Limits for Petitions, Motions, Oppositions, and Replies

The Office is clarifying that a statement of material fact in an opposition or reply is optional.  37 C.F.R. §§ 42.23 and 42.24 are amended to make this clear.

Discovery

The Office is also clarifying that routine discovery includes only the cross-examination of affidavit testimony.  Nothing more.

Taking Testimony

37 C.F.R. § 42.53(c)(2) is being amended to clarify that uncompelled direct testimony must be in the form of an affidavit.

Motions in Limine

The rules do not provide for motions in limine, but the term was include at 37 C.F.R. § 42.64.  This reference is being deleted.

Oppositions

37 C.F.R. § 42.64(b)(1) is being amended to require the filing of objections to the admissibility of evidence, rather than just service as originally required.  The problem stemmed from the fact that motions to exclude evidence require identification in the record when the objection was first made.  However, when they were only served and not filed, the objections did not become part of the record.  This amendment solves that problem.

Decision on Petition or Motion

The Office is clarifying that a party may only file one request for rehearing as a matter of right.

The Office also made a couple of changes to the transitional program for covered business method patent review.  First, it was clarified that the pendency of the review can be extended.  Second, the Office clarified that a petitioner is barred from challenging the validity of patent if it already filed a civil action challenging the validity of a claim.

As mentioned, there will be a second rules package that will hopefully come out later this year.  According to Director Lee's announcement of about two months ago, we can expect to see in this second package, modifications to the motion to amend process; adjustments to the evidence a patent owner can provide in a preliminary response; and clarification of the claim construction standard as applied to expired patents in AIA proceedings.  We will, of course, report the new rules package once they are published.

And finally, we do wish to acknowledge that on the same day as this rules package, PTAB Chief Judge James Smith announced that he will be stepping down from that position later this year (according to a report from Law360).  Judge Smith was appointed to the position in 2011, when it was known as the Board of Patent Appeals and Interferences.  In addition, Judge Smith has been the only Chief Judge of the PTAB, which was created by the America Invents Act ("AIA") in 2012.  Not only was Judge Smith required to oversee the implementation of the new post-grant proceedings introduced by the AIA, but he was responsible for handling the backlog of appeals in other cases, such as prosecution appeals and reexaminations.  Nevertheless, Judge Smith in generally thought to have performed admirably in his tenure at that position.  We wish Judge Smith success in his future endeavors, and thank him for a job well done over the past four years.

For those interested in these topics, and would like to get (or share) more recent happening at the PTAB, we would like to remind everyone of the PTAB TRIALS group on LinkedIn, which provides up-to-date information on IPR, PGR and CBM Info.  That group will continue to cover the roll-out of the new AIA post-issuance proceeding rule packages.  And, of course, we will continue to cover any significant updates here on Patent Docs.

Biogen MA, Inc. v. Japanese Foundation for Cancer Research (Fed. Cir. 2015)

By Kevin E. Noonan --

The Federal Circuit affirmed a decision by the U.S. District Court for the District of Massachusetts that it lacked subject matter jurisdiction under 35 U.S.C. § 146 pursuant to changes in the statute provided by the Leahy-Smith America Invents Act, in Biogen MA, Inc. v. Japanese Foundation for Cancer Research.  Biogen brought suit after receiving an unfavorable PTAB determination in an interference, a proceeding eliminated by other changes in the AIA for patents having an earliest effective filing date after March 15, 2013.  At issue here was whether these AIA changes in the scope of appeals applied to interferences instituted after September 15, 2012 under circumstances wherein each party had an earliest effective filing date prior to the effective date of the change from the "first to invent" to "first inventor to file" standard.

This interference (No. 105,939) is one in a line with long provenance in biotechnology patent law, being related to the three-way interference that resulted in the Federal Circuit decision in Fiers v. Revel (v. Sugano, the latter inventor having been granted priority to claims for isolated human β-interferon DNA). That case stands for the proposition that conception of an invention comprising an isolated nucleic acid molecule requires that the molecule actually be isolated.  It is a decision that directly supports the further development of the Federal Circuit's written description jurisprudence, from Regents of the University of California v. Eli Lilly & Co. through Ariad v. Eli Lilly.

In the case at bar, the PTAB held that one of the inventors, Walter Fiers, was estopped by losses in two earlier interferences "covering the same subject matter" (the opinion notes that the '939 interference was directed to β-interferon protein).  The District Court determined that the AIA eliminated district court jurisdiction for appeals of PTAB decisions in interferences, and transferred the case to the Federal Circuit (which undoubtedly has jurisdiction under 35 U.S.C. § 141).  The Federal Circuit panel affirmed the District Court on the procedural question and the PTAB on the substantive question regarding interference estoppel, in a decision by Judge Dyk joined by Judges Schall and Chen.

Regarding the procedural issue, the panel decided the "threshold issue" of whether the Federal Circuit had jurisdiction to decide whether the District Court had properly decided that it did not have jurisdiction (a decision that the Japanese Foundation contended was not reviewable).  The Federal Circuit held that the District Court's decision was reviewable, citing In re Teles AG Informationstechnologien, 747 F.3d 1357 (Fed. Cir. 2014).  That case was one "virtually indistinguishable" from this one, but there the Court did not "explicitly discuss the basis for adjudicating the district court's jurisdiction" so the panel set forth its grounds in this opinion.  The opinion relied on its own "'inherent jurisdiction to determine [its] own jurisdiction,'" citing  C.R. Bard, Inc. v. Schwartz, 716 F.2d 874, 877 (Fed. Cir. 1983) (citing United States v. United Mine Workers of Am., 330 U.S. 258 (1947)), and noted that Congress had "provided two mutually exclusive avenues of review [of adverse interference decisions] under § 146 and § 141."  This proposition finds support not only in the Court's own jurisprudence (including  AbbVie Deutschland GmbH v. Janssen Biotech, Inc., 759 F.3d 1285, 1296 (Fed. Cir. 2014)), but more importantly under controlling Supreme Court precedent.  Hoover Co. v. Coe, 325 U.S. 79, 84-85 (1945) (regarding an earlier version of the Patent Act having similar alternate provisions, wherein the Court "thoroughly reviewed the legislative history of the patent acts since 1836, which revealed continued maintenance of alternative paths of review").  The opinion notes that these procedural alternatives have been upheld "uniform[ly]" by appellate courts and that choosing one option constitutes an "irrevocable election."  In such an "either/or" situation, the question of whether the Court can properly exercise jurisdiction depends on whether the District Court was correct in determining that it did not have jurisdiction, contrary to the Foundation's position.

The panel determined that the AIA stripped district courts of their jurisdiction over adverse interference decisions.  In reaching its decision, that Court reviewed the provisions of the AIA to understand whether the new law changed availability of § 146 challenge of patent decisions for interferences declared after September 15, 2012 (one year after enactment of the law and the time when changes in other provisions of the law, such as the change from inter partes re-examination to inter partes review became effective).  The opinion does not rely solely on the AIA, however, but also considered revisions to the AIA enacted by the Leahy-Smith America Invents Technical Corrections Act, Pub. L. No. 112– 274, 126 Stat. 2456 (2013).  In part this was necessary because the panel found the "effective date" provisions to be "far from a model of clarity," containing a "hodgepodge" of "express" and "implicit reservations" of pre-AIA provisions "and sometimes simply silence."  With this backdrop, the opinion focuses on the parties' contentions regarding the meaning of § 3(n)(1) of the AIA:

(1) IN GENERAL.—Except as otherwise provided in this section, the amendments made by this section shall take effect upon the expiration of the 18-month period beginning on the date of the enactment of this Act [i.e., March 16, 2013], and shall apply to any application for patent, and to any patent issuing thereon, that contains or contained at any time—
    (A) a claim to a claimed invention that has an effective filing date as defined in section 100(i) of title 35, United States Code, that is on or after  the effective date described in this paragraph; or
    (B) a specific reference under section 120, 121, or 365(c) of title 35, United States Code, to any patent or application that contains or contained at any time such a claim.

The opinion admits that this section is "silent" regarding interferences.  Biogen relied upon this silence to support its position that pre-AIA provisions of the Patent Act, including the alternative choices for forum of appeals from adverse interference decisions, remain effective for interferences declared after September 15, 2012.  The panel disagreed and found that "Congress specifically addressed the manner of judicial review of Board decisions in continuing interference proceedings" and that these provisions control.  Specifically, the opinion cites §6(f)(3)(C), which provides:

(C) APPEALS.—The authorization to appeal or have remedy from derivation proceedings in sections 141(d) and 146 of title 35, United States Code, as amended by this Act, and the jurisdiction to entertain appeals from derivation proceedings in section 1295(a)(4)(A) of title 28, United States Code, as amended by this Act, shall be deemed to extend to any final decision in an interference that is commenced before the effective date set forth in paragraph (2)(A) of this subsection [i.e., September 16, 2012] and that is not dismissed pursuant to this paragraph.

The opinion recognized that this section did not address appeals in interferences declared after September 15, 2012 but asserted that Congress "corrected [its] omission" in § 1(k)(3) of the (AIA) Technical Corrections Act:

(3) REVIEW OF INTERFERENCE DECISIONS.—The provisions of sections 6 and 141 of title 35, United States Code, and section 1295(a)(4)(A) of title 28, United States Code, as in effect on September 15, 2012, shall apply to interference proceedings that are declared after September 15, 2012, under section 135 of title 35, United States Code, as in effect before the effective date under section 3(n) of the Leahy-Smith America Invents Act.  The Patent Trial and Appeal Board may be deemed to be the Board of Patent Appeals and Interferences for purposes of such interference proceedings.

The Federal Circuit found express provisions regarding appellate review under § 141 for interferences declared after September 16, 2012; the absence of any corresponding provisions for review under § 146 was enough for the Court to conclude that no such provision survived the changes in U.S. patent law wrought by the AIA.  Taking this silence in combination with the provisions of § 6(f)(3)(C) of the AIA, the panel concluded that "pre-AIA § 146 review was eliminated for interference proceedings declared after September 15, 2012."

The basis for this conclusion bears some consideration from the Court, which asserted in the opinion that the panel relied on the "basic tenet of statutory interpretation that the specific governs the general."  This tenet is illustrated in the opinion by Supreme Court precedent including RadLAX Gateway Hotel, LLC v. Amalgamated Bank, 132 S. Ct. 2065 (2012), and Gozlon-Peretz v. United States, 498 U.S. 395 (1991).  In the instant case, the opinion states that "even if the general effective date provision in § 3(n)(1) suggests that in general Congress preserved pre-AIA provisions for pre-March 16, 2013, patent applications, it does not follow that we should myopically apply § 3(n)(1) independently of the specific provisions in AIA § 6(f)(3)(C) and § 1(k)(3)."  The opinion discerns that Congress intended to target "'deliberately targeted specific problems with specific solutions,'" citing RadLAX that the Court "cannot ignore."  The panel decided that it "must accordingly follow the express provisions in the statute" (forgetting, it would seem, the lack of clarity the Court noted earlier in its opinion) and characterized Biogen's arguments to the contrary to be "convoluted."

Turning to the merits, the panel agreed with the PTAB that "estoppel by judgment" applies here, defined as situations where "'a losing party in a previous interference between the same parties'" tries to patent a claim 'not patentably distinct from the counts in issue in that [prior] interference,'" citing Woods v. Tsuchiya, 754 F.2d 1571, 1579 (Fed. Cir. 1985).  "Claims that are not patentably distinct from lost counts were already adjudicated in the prior interference and are thus conclusive," said the Court and agreed with the Foundation that "Fiers failed to meet his burden to show patentable distinctness to avoid interference estoppel by judgment."  The Court also relied upon the Board's reasoning that "'[i]n light of [the fact] that DNA and the known genetic code indicating which DNA sequences encode each amino acid, those of skill in the art would have considered the polypeptide Fiers now claims to have been obvious.'"  Included in the litany of failures was Biogen's assertion of a Restriction Requirement in Biogen's application at issue in the interference, with the Court holding that issuing this paper is not determinative of patentable distinctness but as being limited to "evidence that the examiner thought that there were 'two or more independent and distinct inventions' claimed in a single application," citing 35 U.S.C. § 121; 37 C.F.R. § 1.142; MPEP § 802.01.  The panel characterized restriction requirements as being "primarily for administrative convenience" and as "not represent[ing] a final determination that the relevant claims are patentably distinct," citing Applied Materials, Inc. v. Advanced Semiconductor Materials Am., Inc., 98 F.3d 1563, 1568 (Fed. Cir. 1996).  The panel showed similar disregard for similar arguments regarding the Office declaring separate interferences, also emphasizing the "discretionary" nature of these decisions.

The panel decision cannot properly be contested as being "wrong" per se, but it can be recognized that it is based on the absence of express provisions regarding district court review of interferences declared after September 15, 2012.  As such, it should be a simple matter for Congress to restore the status quo ante (the AIA) the next time it considers "technical amendments" to the AIA or other revisions to the Patent Act.

Biogen MA, Inc. v. Japanese Foundation for Cancer Research (Fed. Cir. 2015)
Panel: Circuit Judges Dyk, Schall, and Chen
Opinion by Circuit Judge Dyk

Senator Asks Department of Veteran Affairs to Break Patents on Hepatitis C Drugs

By Donald Zuhn --

Last week, in a letter addressed to the Secretary of the U.S. Department of Veteran Affairs, Senator Bernard Sanders (I-VT) urged Secretary Robert McDonald to use his authority as Secretary "to break the patents on Hepatitis C medications for the treatment of veterans suffering with the disease."  Senator Sanders (at right) notes in the letter that as Chairman of the Senate Committee of Veterans' Affairs, he held a hearing in December 2014 regarding the impact of Hepatitis C drug pricing on veterans' access to treatment, and "raised concerns that the price of these new Hepatitis C drugs, specifically Sovaldi, which is manufactured by Gilead Sciences, even when discounted, would preclude veterans from accessing these life-changing drugs."

With regard to Solvaldi, Senator Sanders indicates that the drug is priced at $1,000 per pill, or about $84,000 for a course of treatment, and contends that "[t]his price was not a function of cost.  It was, pure and simple, an abuse of monopoly power."  As a result of the drug's price, the Senator states that "the concerns I raised last year have become a reality -- VA is being forced to stop enrollment of new patients in treatment because of lack of funds."

While suggesting that one solution to the problem would be for "Gilead Sciences to simply provide the drug to VA at no cost, as they have done abroad in the Republic of Georgia, India, and other places throughout the world with high rates of HCV infection," the letter notes that "the company has not stepped up to do this for our country's veterans," and declares that "[i]nstead, they have prioritized an outrageous compensation package for Gilead's CEO John Maitin, valued at over $190 million, including stock options and shares."

Senator Sanders proposes an alternative course of action to Secretary McDonald, asking the Secretary "to utilize federal law, specifically 28 USC § 1498, to break the patents on these drugs to authorize third parties to manufacture or import them for government use."  The Senator concludes that "I cannot think of a more clear-cut situation where the government use provision should be applied," adding that "[o]ur nation's veterans cannot, and should not, be denied treatment while drug companies rake in billions of dollars in profits."

In the letter, Senator Sanders suggests that Secretary McDonald utilize 28 U.S.C. § 1498.  Section 1498(a) of Title 28 provides that:

§ 1498. Patent and copyright cases

(a) Whenever an invention described in and covered by a patent of the United States is used or manufactured by or for the United States without license of the owner thereof or lawful right to use or manufacture the same, the owner’s remedy shall be by action against the United States in the United States Court of Federal Claims for the recovery of his reasonable and entire compensation for such use and manufacture.  Reasonable and entire compensation shall include the owner’s reasonable costs, including reasonable fees for expert witnesses and attorneys, in pursuing the action if the owner is an independent inventor, a nonprofit organization, or an entity that had no more than 500 employees at any time during the 5-year period preceding the use or manufacture of the patented invention by or for the United States.

Nothwithstanding the preceding sentences, unless the action has been pending for more than 10 years from the time of filing to the time that the owner applies for such costs and fees, reasonable and entire compensation shall not include such costs and fees if the court finds that the position of the United States was substantially justified or that special circumstances make an award unjust.

For the purposes of this section, the use or manufacture of an invention described in and covered by a patent of the United States by a contractor, a subcontractor, or any person, firm, or corporation for the Government and with the authorization or consent of the Government, shall be construed as use or manufacture for the United States. . . .

A discussion of the history of § 1498 can be found at pages 10-14 of Zoltek Corp. v. United States (Fed. Cir. 2012).  The opinion notes that a precursor to the section was initially enacted by Congress in 1910 in response to the Supreme Court's decision in Schillinger v. United States (1894), where the Court held that patent infringement was a tort for which the Government had not waived sovereign immunity, and as a result, determined that a patentee lacked a remedy for infringement by the United States.  In William Cramp & Sons Ship & Engine Bldg. Co. v. Int’l Curtis Marine Turbine Co., 246 U.S. 28 (1918), the Supreme Court applied the 1910 Act to the issue of patent infringement by government contractors who constructed warships for the U.S. Navy during World War I, finding that the 1910 Act did not shield the contractors from infringement.  The Acting Secretary of the Navy, Franklin D. Roosevelt, responded to the Court's decision by writing to the Senate Committee of Naval Affairs that:

[I]t seems necessary that amendment be made of the Act of June 25, 1910 [as] the decision is, in effect, . . . that a contractor for the manufacture of a patented article for the government is not exempt . . . from injunction and other interference through litigation by the patentee[, and as a result] manufacturers are exposed to expensive litigation, involving the possibilities of prohibitive injunction payment of royalties, rendering of accounts, and payment of punitive damages, and they are reluctant to take contracts that may bring such severe consequences.

Acting Secretary Roosevelt proposed an amendment in which the Government waived sovereign immunity for its own unlawful use or manufacture of a patented invention, but also assumed liability when its contractors did so for the Government.

Court Report

        By Sherri Oslick --

About Court Report:  Each week we will report briefly on recently filed biotech and pharma cases.

Horizon Pharma, Inc. et al. v. Actavis Laboratories FL., Inc. et al.
3:15-cv-03322; filed May 13, 2015 in the District Court of New Jersey

• Plaintiffs:  Horizon Pharma, Inc.; Pozen Inc.
• Defendants:  Actavis Laboratories FL., Inc.; Actavis Pharma, Inc.; Actavis, Inc.

Horizon Pharma, Inc. et al. v. Dr. Reddy's Laboratories Inc. et al.
3:15-cv-03324; filed May 13, 2015 in the District Court of New Jersey

• Plaintiffs:  Horizon Pharma, Inc.; Pozen Inc.
• Defendants:  Dr. Reddy's Laboratories Inc.; Dr. Reddy's Laboratories Ltd.

Horizon Pharma, Inc. et al. v. Lupin Ltd. et al.
3:15-cv-03326; filed May 13, 2015 in the District Court of New Jersey

• Plaintiffs:  Horizon Pharma, Inc.; Pozen Inc.
• Defendants:  Lupin Ltd.; Lupin Pharmaceuticals Inc.

Horizon Pharma, Inc. et al. v. Mylan Pharmaceuticals Inc. et al.
3:15-cv-03327; filed May 13, 2015 in the District Court of New Jersey

• Plaintiffs:  Horizon Pharma, Inc.; Pozen Inc.
• Defendants:  Mylan Pharmaceuticals Inc.; Mylan Laboratories Ltd.; Mylan, Inc.

The complaints in these cases are substantially identical.  Infringement of U.S. Patent Nos. 8,852,636 ("Pharmaceutical Compositions for the Coordinated Delivery of NSAIDs" issued October 7, 2014), 8,858,996 (same title, issued October 14, 2014), in conjunction with defendants' filing of an ANDA to manufacture a generic version of Horizon's Vimovo® Delayed-Release (naproxen and esomeprazole magnesium, used to relieve the signs and symptoms of osteoarthritis, rheumatoid arthritis, and ankylosing spondylitis, and to decrease the risk of stomach (gastric) ulcers in patients at risk of developing stomach ulcers from treatment with non-steroidal anti-inflammatory drugs (NSAIDs)).  View the Actavis complaint here.

Senju Pharmaceutical Co., Ltd. et al. v. Innopharma Licensing, Inc. et al.
1:15-cv-03240; filed May 8, 2015 in the District Court of New Jersey

• Plaintiffs:  Senju Pharmaceutical Co., Ltd.; Bausch & Lomb Inc.; Bausch & Lomb Pharma Holdings Corp.
• Defendants:  Innopharma Licensing, Inc.; Innopharma Licensing, LLC; Innopharma, Inc.; Innopharma, LLC; Mylan Pharmaceuticals, Inc.; Mylan Inc.

Infringement of U.S. Patent Nos. 8,129,431 ("Aqueous Liquid Preparation Containing 2-amino-3-(4-bromobenzoyl)phenylacetic acid," issued March 6, 2012), 8,669,290 (same title, issued March 1, 2014), 8,754,131 (same title, issued June 17, 2014), 8,871,813 (same title, issued October 28, 2014), and 8,927,606 (same title, issued January 6, 2015) against Mylan, and the '606 patent against Innopharma, following a Paragraph IV certification as part of Innopharma's filing of an ANDA to manufacture a generic version of B&L's Prolensa® (bromfenac ophthalmic solution, used to treat postoperative inflammation and reduction of ocular pain in patients who have undergone cataract surgery).  View the complaint here.

Jazz Pharmaceuticals, Inc. v. Amneal Pharmaceuticals, LLC et al.
2:15-cv-03217; filed May 7, 2015 in the District Court of New Jersey

• Plaintiff:  Jazz Pharmaceuticals, Inc.
• Defendants:  Amneal Pharmaceuticals, LLC; Par Pharmaceutical, Inc.; Sun Pharmaceutical Industries Ltd.; Ohm Laboratories Inc.; Ranbaxy Inc.

Infringement of U.S. Patent No. 8,952,062 ("Microbiologically Sound and Stable Solutions of Gamma-Hydroxybutyrate Salt for the Treatment of Narcolepsy," issued February 10, 2015) following a Paragraph IV certification as part of defendants' filing of an ANDA to manufacture a generic version of Jazz's Xyrem® (sodium oxybate, used to treat narcolepsy).  View the complaint here.

Zoetis LLC et al. v. Roadrunner Pharmacy, Inc.
2:15-cv-03193; filed May 6, 2015 in the District Court of New Jersey

• Plaintiffs:  Zoetis LLC; Zoetis Services LLC; Zoetis US LLC
• Defendant:  Roadrunner Pharmacy, Inc.

Infringement of U.S. Patent Nos. 8,133,899 ("Pyrrolo[2,3-d]pyrimidine Compounds," issued March 13, 2012) and 8,987,283 (same title, issued March 24, 2015) based on Roadrunner's manufacture and sale of a oclacitinib free base product, sold to be equivalent to Zoetis' APOQUEL® (oclacitinib maleate, used for the treatment of pruritus and allergic reactions in dogs).  View the complaint here.

Conference & CLE Calendar

May 19, 2015 - "Best Practices for Cost-Effective Filing of PCT and EPO Patent Applications" (Technology Transfer Tactics) - 1:00 to 2:00 pm (Eastern)

May 19-21, 2015 - EU Pharmaceutical Law Forum*** (Informa Life Sciences) - Brussels, Belgium

May 20, 2015 - "Never Been a Better Time (For IP) Than Right Now?" (Intellectual Property Owners Association (IPO) European Practice Committee) - London, UK

May 21, 2015 - "USPTO and Plain Meaning of Terms" (Intellectual Property Owners Association) - 2:00 to 3:00 pm (ET)

May 27, 2015 - "Patent Term Adjustment: 2015 Final Rules" (The Knowledge Group) - 3:00 to 5:00 pm (ET)

May 28, 2015 - "Patent Exhaustion and Its Impact on Patent Licensing" (McDonnell Boehnen Hulbert & Berghoff LLP) - 10:00 am to 11:15 am (CT)

May 28, 2015 - "Hedge Fund IPR Challenges to Pharma Patents: Strategies to Strengthen Patents to Withstand Attack" (Strafford) - 1:00 to 2:30 pm (EDT)

May 28, 2015 - "The New EU Unitary Patent & Unified Patent Court: Strategic Considerations for US Applicants/Patentees" (American Bar Association (ABA) Center for Professional Development, Section of Intellectual Property Law, Section of International Law, and Young Lawyers Division) - 1:00 to 2:30 pm (ET)

May 28, 2015 - "Inter Partes Review Strategy and Trends in the Life Sciences Industry: Implications for Patent Prosecutors and Litigators" (Morrison & Foerster LLP) - 8:30 to 10:00 am (PDT)

June 1-2, 2015 - Biosimilars*** (American Conference Institute) - New York, NY

June 4, 2015 - "Navigating Section 112(a) Enablement and Written Description -- Withstanding 112(a) Rejections and Attacks on Patent Validity and Patentability" (Strafford) - 1:00 to 2:30 pm (EDT)

June 9-10, 2015 - Due Diligence Summit for Life Sciences*** (ExL Events) - Boston, MA

June 15-17, 2015 - Fundamentals of Patent Prosecution 2015: A Boot Camp for Claim Drafting & Amendment Writing (Practising Law Institute) - New York, NY

June 15-18, 2015 - BIO International Convention (Biotechnology Industry Organization) - Philadelphia, PA

July 8-10, 2015 - Fundamentals of Patent Prosecution 2015: A Boot Camp for Claim Drafting & Amendment Writing (Practising Law Institute) - San Francisco, CA

***Patent Docs is a media partner of this conference or CLE

IPO Webinar on Examiner Training Guidelines for Claim Interpretation

The Intellectual Property Owners Association (IPO) will offer a one-hour webinar entitled "USPTO and Plain Meaning of Terms" on May 21, 2015 beginning at 2:00 pm (ET).  Brenton Babcock, Knobbe of Martens, Olson & Bear, LLP; Gary Ganzi of Evoqua Water Technologies LLC; and Joseph Weiss of the U.S. Patent & Trademark Office will discuss new examiner training guidelines intended to make the record clearer during prosecution by explaining claim interpretation as necessary, explore the implications of this change for patent prosecution and litigation, and explain how the new guidelines will work in practice.

The registration fee for the webinar is $130 (government and academic rates are available upon request).  Those interested in registering for the webinar can do so here.

Webinar on Unitary Patent & Unified Patent Court

The American Bar Association (ABA) Center for Professional Development, Section of Intellectual Property Law, Section of International Law, and Young Lawyers Division will be offering a live webinar entitled "The New EU Unitary Patent & Unified Patent Court: Strategic Considerations for US Applicants/Patentees" on May 28, 2015 from 1:00 to 2:30 pm (ET).  Margaret M. Welsh (moderator) of Sughrue Mion, PLLC; Dr. Bernd Aechter of Ter Meer Steinmeister & Partner (Munich, Germany); Will Jones II, Group IP Counsel (retired), Air Products and Chemicals, Inc.; Brad J. Hattenbach of Dorsey & Whitney LLP; and Charles D. Larsen of Ropes & Gray LLP will discuss strategic considerations for U.S. applicants/patentees in view of the new EU Unitary Patent and Unified Patent Court.

The registration fee for the webcast is $150 for members, $95 for sponsor members, and $195 for the general public.  Those interested in registering for the webinar, can do so here.

Webcast on Patent Term Adjustment

The Knowledge Group will offer a live webcast entitled "Patent Term Adjustment: 2015 Final Rules" on May 27, 2015 from 3:00 to 5:00 pm (ET).  Mark Thronson of Dickstein Shapiro LLP; Robert Irani of Bennett Jones; and John C. Donch, Jr. of Volpe and Koenig, PC will review and discuss the nuances and changes in regulations regarding Patent Term Adjustment (PTA) and help attendees understand when to file a Request for Continued Examination (RCE) with the U.S. Patent and Trademark Office (USPTO). The panel will also discuss the consequences of the USPTO's final rule on PTA and provide best practices for optimal filing.

The registration fee for the webcast is $299 to $349 (regular rate) or $149 (government/nonprofit rate).  Those registering by May 17, 2015 will receive a $100 discount of the regular rate.  Those interested in registering for the webinar can do so here.

Webinar on Inter Partes Review Strategy and Trends in the Life Sciences Industry

Morrison & Foerster LLP will be offering a webinar entitled "Inter Partes Review Strategy and Trends in the Life Sciences Industry: Implications for Patent Prosecutors and Litigators" on May 28, 2015 from 8:30 to 10:00 am (PDT).  Tina E. Hulse, Administrative Patent Judge, Silicon Valley U.S. Patent Trademark Office; and Michael Jacobs, Matthew Kreeger, and Cary Miller of Morrison & Foerster LLP will highlight several concrete strategies for IPR petitions in pharmaceutical and biotechnology cases.  Topics to be covered in the web conference will include:

• How life sciences companies are integrating IPRs into their patent litigation strategies and patent portfolio management;
• The types of claims and challenges involved in life sciences IPRs
• The use of IPRs in ANDA/Hatch-Waxman litigation;
• Factors to consider in choosing ex parte reexamination, IPR, or litigation as the best approach to challenging validity in life sciences cases; and
• The interplay amongst IPRs, prosecution, and litigation, including whether or not to institute an IPR and its potential impact on ongoing prosecution and litigation.

While there is no cost to participate in the program, registration is required.  Those interested in attending the webinar can register here.

Classen Immunotherapies, Inc. v. Elan Pharmaceuticals, Inc. (Fed. Cir. 2015)

By Andrew Williams --

The Hatch Waxman statute created a safe-harbor provision, found at 35 U.S.C. § 271(e)(1), that allows ANDA filers and others to practice patented inventions without fear of infringement liability, provided the acts are "solely for uses reasonably related to the development and submission of information" to the FDA.  Even though the plain language of the statute appears to indicate that the exemption to infringement would be narrow, the Supreme Court and the Federal Circuit have been gradually expanding its scope.  Earlier this week, the Federal Circuit continued this expansion in Classen Immunotherapies, Inc. v. Elan Pharmaceuticals, Inc.  Not only does the safe-harbor provision apply to post-filing activity, as previous cases have indicated, but the safe harbor can also be sought by NDA holders that happen to practice someone else's patents for the purposes of FDA submissions.

The relevant part of 35 U.S.C. § 271(e)(1) reads:

It shall not be an act of infringement to make, use, offer to sell, or sell within the United States or import into the United States a patented invention . . . solely for uses reasonably related to the development and submission of information under a Federal law which regulates the manufacture, use, or sale of drugs or veterinary biological products.

The Supreme Court began the expansion of this provision in Merck KGaA v. Integra Lifesciences I, Ltd., 545 U.S. 193 (2005).  That case arose from a Federal Circuit appeal, in which that court held that the safe harbor did not apply to preclinical testing because it is too far removed, or "back down the chain of experimentation," for the development of submitted information to the FDA.  The Supreme Court could not find support in the statute to exclude "certain information from the exemption on the basis of the phase of research in which it is developed or the particular submission in which it could be included."  Id. at 202.  Thereafter, preclinical data enjoyed the safe harbor.

With regard to post-FDA filing activity, the Federal Circuit initially indicated that it was not a "phase of research" entitled to the exemption.  In Classen Immunotherapies, Inc. v. Biogen IDEC, presumably unrelated to the present case, a majority of the merits panel (then-Chief Judge Rader joined by Judge Newman) held that "routine" post-approval submissions are outside the safe harbor (over a vigorous dissent by Judge Moore).  In the following case, Momenta Pharm. v. Amphastar Pharm., the roles were reversed, with Judge Moore finding herself in the majority (with Judge Dyk), and then-Chief Judge Rader filing a dissent.  In this case, the Federal Circuit interpreted the statutory language broadly, stating that the "language unambiguously applies to submissions under any federal law, providing that the law 'regulates the manufacture, use, or sale of drugs.'"  Therefore, according to current Federal Circuit jurisprudence, the safe harbor is not limited to pre-approval activities (Momenta); it is not limited to information that is actually submitted to the FDA, provided the FDA requires that records be maintained for possible inspection (Momenta); and it is okay if the information has alternative uses, such as for fund raising or other business purposes (Abtox, Inc. v. Exitron Corp.).

In the present case, the patent at issue (U.S. Patent No. 6,584,472) was directed to "a method for accessing and analyzing data on a commercially available drug to identify a new use of that drug, and then commercializing that new use."  The representative method claim (claim 36) depends from claim 33 cancelled during reexamination:

33.  [cancelled during reexamination]  A method for creating and using data associated with a commercially available product, wherein the method comprises the steps of:
    accessing at least one data source, comprising together or separately, adverse event data associated with exposure to or use of the product and commercial data regarding marketing, sales, profitability or related information pertaining to the product;
    analyzing the accessed data to identify (i) at least one new adverse event associated with exposure to or use of the product, (ii) at least one new use for the product responsive to identification of the at least one new adverse event, and (iii) the potential commercial value of the at least one new use for the product; and
    commercializing the newly identified product information based upon the analyzed data.

36.  The method of claim 33, wherein the commercializing step comprises formatting the data relating to at least one new adverse event associated with exposure to, or use of the product, or documenting same, such that a manufacturer or distributor of the product must inform consumers, users or individuals responsible for the user, physicians or prescribers about at least one new adverse event associated with exposure to or use of the product.

There were also kit claims, claim 59 of which is representative:

59.  A proprietary kit comprising (i) product and (ii) documentation notifying a user of the product of at least one new adverse event relating to the product, wherein determination of the new adverse event is based upon the data provided by the method of claim 36.

And if these claims appear to have patent eligibility issues, the Court pointed out that 35 U.S.C § 101 issues were not raised on appeal.

Elan had filed an NDA for metaxalone, a muscle relaxant, which it markets under the brand-name Skelaxin.  In 2001, Elan learned that some third party studies called into question the designation of the metaxalone tablets.  Elan responded by conducting additional clinical studies showing that the bioavailability of Skelaxin was significantly increased when administered with food.  As a result, Elan filed a supplemental NDA (sNDA), and sought patent protection using this data, the claims of which were subsequently invalidated in another litigation.  Classen sued Elan, alleging infringement of the '472 patent for studying the effects of food on bioavailability, using the data to identify a new use, and commercializing the new use.  Elan argued that all of this activity was protected by 271(e)(1).

With regard to the clinical studies, the Federal Circuit held that "Elan's clinical study and its FDA submissions" were well within the scope of the protection.  Elan had developed this information for submission to the FDA in order to change the product label, and the Court found this to be anything but "routine."  This addressed any potential concerns of the impact of the Classen case.  With regard to the patent filings and kits being developed, the Federal Circuit found that the District Court did not determine whether these post-filings activities would fall within the exemption.  Therefore, the case was vacated and remanded.

Important in this decision, the Federal Circuit pointed out that the mere disclosure or use of the information would not be an "act of infringement."  Also, the Court provided "the following observation" about the cases.  First, filing a patent application is generally not an act of infringement.  "It is the act of approaching an agency of the government in order to obtain a limited privilege and to fulfill a public."  Second, the use of such information "submitted to the FDA on the product label after sNDA approval generally cannot be an infringement."  In fact, the opposite is true -- it is required by law that this information be submitted to the FDA.  But, the Court left open the question whether there was any use or commercializing which would not be exempt.  For those answers, we will have to stay tuned.

Classen Immunotherapies, Inc. v. Elan Pharmaceuticals, Inc. (Fed. Cir. 2015)
Panel: Chief Judge Prost, Circuit Judge Lourie, and District Judge Gilstrap (sitting by designation)
Opinion by Circuit Judge Lourie

Court Report

        By Sherri Oslick --

About Court Report:  Each week we will report briefly on recently filed biotech and pharma cases.

Galderma Laboratories LP et al. v. Glenmark Generics Inc USA
3:15-cv-01416; filed May 6, 2015 in the Northern District of Texas

• Plaintiffs:  Galderma Laboratories LP; Galderma SA; Galderma Research & Development SNC
• Defendant:  Glenmark Generics Inc USA; Glenmark Generics Ltd.

Infringement of U.S. Patent Nos. 8,071,644 ("Combinations of Adapalene and Benzoyl Peroxide for Treating Acne Lesions," issued December 6, 2011), 8,080,537 (same title, issued December 26, 2011), 8,129,362 ("Combination/Association of Adapalene and Benzoyl Peroxide for Treating Acne Lesions," issued March 6, 2012), 8,445,543 ("Combinations of Adapalene and Benzoyl Peroxide for Treating Acne Lesions," issued May 21, 2013), and 8,809,305 ("Administration of Adapalene and Benzoyl Peroxide for the Long-Term Treatment of Acne Vulgaris," issued August 19, 2014) following a Paragraph IV certification as part of Glenmark's filing of an ANDA to manufacture a generic version of Galderma's Epiduo® Gel (adapalene and benzoyl peroxide, used to treat acne vulgaris).  View the complaint here.

Vanda Pharmaceuticals Inc. v. Inventia Healthcare PVT Ltd.
1:15-cv-00362; filed May 5, 2015 in the District Court of Delaware

Infringement of U.S. Patent No. 8,586,610 ("Methods for the Administration of Iloperidone," issued November 19, 2013) in conjunction with Inventia's filing of an ANDA to manufacture a generic version of Vanda's Fanapt® (iloperidone, used for the acute treatment of adults with schizophrenia).  View the complaint here.

Apotex Inc. et al. v. Lupin Ltd. et al.
1:15-cv-00357; filed May 4, 2015 in the District Court of Delaware

• Plaintiffs:  Apotex Inc.; Apotex Technologies Inc.; SmithKline Beecham (Cork) Ltd.; SmithKline Beecham Ltd.
• Defendants:  Lupin Ltd.; Lupin Pharmaceuticals, Inc.

Apotex Inc. et al. v. Lupin Ltd. et al.
2:15-cv-00599; filed May 1, 2015 in the Eastern District of Texas

• Plaintiffs:  Apotex Inc.; Apotex Technologies, Inc.; SmithKline Beecham (Cork) Ltd.; SmithKline Beecham Ltd. f/k/a Smithkline Beecham PLC
• Defendants:  Lupin Ltd.; Lupin Pharmaceuticals, Inc.

The complaints in these cases are substantially identical.  Infringement of U.S. Patent No. 7,229,640 ("Paroxetine Controlled Release Compositions," issued June 12, 2007) following a paragraph IV certification as part of Lupin's filing of an ANDA to manufacture a generic version of plaintiffs' Paxil CR® (paroxetine hydrochloride controlled release tablets, used to treat depression).  View the E.D. TX complaint here.

Sanofi-Aventis U.S. LLC et al. v. Actavis LLC et al.
3:15-cv-03107; filed May 1, 2015 in the District Court of New Jersey

• Plaintiffs:  Sanofi-Aventis U.S. LLC; Aventis Pharma S.A.; Sanofi
• Defendants:  Actavis LLC; Actavis Elizabeth LLC

Infringement of U.S. Patent No. 8,927,592 ("Antitumoral Use Of Cabazitaxel," issued January 6, 2015) following a Paragraph IV certification as part of Actavis' filing of an NDA (under § 505(b)(2) of the Food, Drug and Cosmetic Act) to manufacture a generic version of Sanofi's Jevtana® (cabazitaxel injection, used in combination with prednisone for the treatment of patients with hormonerefractory metastatic prostate cancer previously treated with a docetaxel-containing treatment regimen).  View the complaint here.

Genes Associated with ALS Identified

By Kevin E. Noonan --

One of the promises of the Human Genome Project was that knowledge of the entirety of the human genetic complement would permit researchers to identify genetic bases for diseases that had been intractable to conventional approaches.  While these efforts have borne equivocal fruit much more slowly that expected or hoped, occasionally there are reports that validate the expectations that were the foundation for much of the support the HGP received during the time before its immediate goal of genome deciphering was achieved.

One such report was published earlier this year in Science using exome analysis (i.e., genetic analyses that focus on the expressed portion of the genome) to identify genes associates with amyotrophic lateral sclerosis (ALS), commonly known as "Lou Gehrig's disease."  Ever since Gehrig's timeless declaration that he was "the luckiest man on the face of the earth," the specter of ALS has haunted mankind.  A progressive, degenerative motor neuron disease that results in the lost of motor control, ALS sufferers face a frightening death.  Despite this, and the impetus the disease has produced to search for a cure, there has been precious little progress since that day in 1939.

While not producing a cure, the results reported in Science at least provide additional clues to where a cure may be found.  Specifically, the researchers studied 2869 ALS patients and 6405 (non-ALS normal) controls and "loss-of-function (LoF)" mutations in one gene in particular, TBK1 encoding TANK-binding kinase were found to be positively associated with ALS in about 1% of cases.  This gene is known to bind to and phosphorylate two genes previously "implicated" in development of the disease, optineurin (OPTN) and p62 (SQSTM1/sequestosome), as well as a number of other proteins involved in innate immunity and autophagy.  Patients having mutations in TBK1 exhibited shorter-than-usual survival times.  In addition, patients having mutations in multiple ALS-associated risk genes presented with symptoms of the disease at an earlier age.  According to the authors, these results "reveal a key role of the autophagic pathway in ALS and suggest specific targets for therapeutic intervention."  Further, "pathogenic variants in OPTN, SQSTM1, or TBK1 would be expected to lead to defects in autophagy and in key innate immunity signaling pathways.  Mutations in these genes might therefore interfere with the normal function of these pathways in maintaining normal cellular riboproteostasis."

The authors* state that their results provide "possible directions for drug screening programs" and "a critical role of autophagy and/or inflammation in disease predisposition."  They conclude:

Our exome sequencing study has identified variants that definitively predispose humans to a sporadic, complex human disease.  Larger exome sequencing studies may reveal identifiable roles for genes that have not yet achieved significant associations.  There is reason for optimism that such studies will begin to fill in an increasingly complete picture of the key genes implicated in ALS, providing multiple entry points for therapeutic intervention.

In the words of an old Yiddish (and Arabic) saying, "from their lips to God's ear."

* The international team was from the following institutions: Center for Applied Genomics and Precision Medicine and Department of Biostatistics and Bioinformatics, Duke University School of Medicine; Duke ALS Clinic and Durham VA Medical Center; HudsonAlpha Institute for Biotechnology; Institute for Genomic Medicine, Department of Neurology, Center for Motor Neuron Biology and Disease, Department of Pediatrics and Medicine, and Department of Biochemistry & Molecular Biophysics, Columbia University; Department of Neurology, University of Massachusetts Medical School; Montreal Neurological Institute, Department of Neurology and Neurosurgery, McGill University; Department of Genetics, Stanford University School of Medicine; Biogen Idec; Neurogenetics DNA Diagnostic Laboratory, Center for Human Genetics Research, Department of Neurology, Massachusetts General Hospital; Department of Neurology, Washington University School of Medicine; Department of Genome Analysis, Academic Medical Center, Amsterdam; Academic Unit of Neurology, Trinity Biomedical Sciences Institute, Trinity College Dublin; Department of Basic and Clinical Neuroscience, King's College London, Institute of Psychiatry, Psychology and Neuroscience; Department of Neurology, Brain Center Rudolf Magnus, University Medical Centre Utrecht; Department of Neurology and Laboratory of Neuroscience, IRCCS Istituto Auxologico Italiano, and Department of Pathophysiology and Transplantation, Dino Ferrari Center, Università degli Studi di Milano, Milan; Cedars Sinai Medical Center; Houston Methodist Hospital; Weill Cornell Medical College of Cornell University; Ludwig Institute for Cancer Research and Department of Neurosciences, University of California, San Diego; Department of Neurology, University of Utah School of Medicine; Department of Pathology and Laboratory Medicine and Department of Neurology, Penn ALS Center and Penn Frontotemporal Degeneration Center, Perelman School of Medicine, University of Pennsylvania; Department of Neurology, Emory University; and Department of Cell Biology, Harvard Medical School.