DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims Status
2. The preliminary amendment filed 05/01/2024 is acknowledged. Claims 3, 5-8, 11-14 and 16-18 are amended. Claims 1-21 are pending and under examination.
Information Disclosure Statement
3. The information disclosure statement (IDS) submitted 08/30/2024 and the references cited therein have been considered, unless indicated otherwise.
The listing of references in the specification is not a proper information disclosure statement such as on page 117. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
4. The use of the term PROMIS Fatigue 7a (page 60), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Please review the specification for other Trademarks and correction is required
Claim Rejections - 35 USC § 112
5. Claims 1-7, and 11-17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are drawn to a method of treating primary mitochondrial myopathy (PMM), the method comprising administering to a subject in need thereof a therapeutically effective amount of an isolated antibody that binds to GDF-15; wherein the primary mitochondrial myopathy is selected from the group consisting of Leigh syndrome, Kearns-Sayre syndrome, Alpers-Huttenlocher syndrome, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), and ataxia neuropathy syndrome; wherein the administration of the anti-GDF15 antibody results in an improvement in one or more signs or symptoms of PMM as compared to before administration; wherein the one or more signs or symptoms of PMM comprise physical fatigue, muscle weakness and/or exercise intolerance; wherein the improvement in one or more signs or symptoms of PMM comprises increased body weight gain, increased lean muscle mass, increased skeletal muscle mass, restored muscle strength, and/or improvement in exercise capacity; wherein the subject does not have cachexia, cancer and/or heart failure; wherein the subject has elevated level and/or activity of GDF15 before administration of the isolated antibody, or antigen-binding fragment thereof; wherein said antibody, or antigen-binding fragment thereof, is administered subcutaneously; wherein said antibody, or antigen-binding fragment thereof, is administered intravenously; wherein said antibody or antigen-binding fragment thereof, is administered about twice a week, once a week, once every two weeks, once every three weeks, once every four weeks, once every five weeks, once every six weeks, once every seven weeks, once every eight weeks, once every nine weeks, once every ten weeks, twice a month, once a month, once every two months, once every three months, or once every four months once every five months, once every six months, once every seven months, once every eight months, once every nine months, once every ten months, once every eleven months or once every twelve months; wherein said antibody or antigen-binding fragment thereof, is administered once a week at a dose between about 0.1 mg and about 1000 mg; wherein said antibody or antigen- binding fragment thereof, is administered once a week at a dose between about 1 mg and about 500 mg; wherein said antibody or antigen-binding fragment thereof, is administered once every two weeks at a dose between about 0.1 mg and about 500 mg; wherein said antibody or antigen-binding fragment thereof, is administered once every four weeks at a dose between about 0.1 mg and about 500 mg.
The specification teaches a method of treating primary mitochondrial myopathy (PMM). The method comprises administering to a subject in need thereof a therapeutically effective amount of an isolated antibody that binds to GDF-15. In some embodiments, the primary mitochondrial myopathy is selected from the group consisting of Leigh syndrome, Kearns-Sayre syndrome, Alpers-Huttenlochersyndrome, mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS), and ataxia neuropathy syndrome. In some embodiments, the administration of the anti-GDF15 antibody results in an improvement in one or more signs or symptoms of PMM as compared to before administration. In some embodiments, the one or more signs or symptoms of PMM comprise physical fatigue, muscle weakness and/or exercise intolerance. In some embodiments, the improvement in one or more signs or symptoms of PMM comprises increased body weight gain, increased lean muscle mass, increased skeletal muscle mass, restored muscle strength, and/or improvement in exercise capacity. In some embodiments, the subject does not have cachexia, cancer and/or heart failure. In some embodiments, the subject has elevated level and/or activity of GDF15 before administration of the isolated antibody, or antigen-binding fragment thereof. The specification further teaches in some embodiments, the antibody, or antigen-binding fragment thereof, is
administered subcutaneously. In some embodiments, the antibody, or antigen-binding fragment thereof, is administered intravenously. In some embodiments, said antibody or antigen-binding fragment thereof, is administered about twice a week, once a week, once every two weeks, once every three weeks, once every four weeks, once every five weeks, once every six weeks, once every seven weeks, once every eight weeks, once every nine weeks, once every ten weeks, twice a month, once a month, once every two months, once every three months, or once every four months once every five months, once every six months, once every seven months, once every eight months, once every nine months, once every ten months, once every eleven months or once every twelve months. In some embodiments, said antibody or antigen-binding fragment thereof, is administered once a week at a dose between about 0.1 mg and about 1000 mg. In some embodiments, said antibody or antigen-binding fragment thereof, is administered once a week at a dose between about 1 mg and about 500 mg. In some embodiments, said antibody or antigen-binding fragment thereof, is administered once every two weeks at a dose between about 0.1 mg and about 500 mg. In some embodiments, said antibody or antigen- binding fragment thereof, is administered once every four weeks at a dose between about 0.1 mg and about 500 mg.
The claims state a method of treating primary mitochondrial myopathy, the method comprising administering to a subject in need thereof a therapeutically effective amount of an isolated antibody that binds to GDF-15. However, the specification provides no guidance regarding any antibody or antigen-binding fragment thereof that specifically binds GDF-15 and does not define all six complementary domain regions (CDRs). The specification does not provide adequate written description to identify the broad genus of the claims because the specification does not disclose a correlation between the necessary structure of the antibody, and the claimed functions to be maintained (i.e. administering antibody that binds GDF-15 to treat PMM). Thus, the specification does not distinguish the claimed genus from others, except by function. Although the term “antibody” does impart some structure, the structure that is common to antibodies is generally unrelated to its specific binding function; therefore, correlation is less likely for antibodies than for other molecules. Accordingly, the specification does not define any structural features commonly possessed by members of the genus because, while the description of an ability of a claimed antibody or antibody fragment thereof may generically describe that molecule’s function, it does not describe the molecule itself. A definition by function does not suffice to define the genus because it is only an indication of what the antibody or antigen-binding fragment thereof does, rather than what it is; therefore it is only a definition of a useful result rather than a definition of what achieves that result. In addition, because the genus of antibodies, is highly variable (i.e. each different antibody capable of binding to GDF-15 would necessarily have a unique sequence of amino acids; see MPEP 2434), the functional characteristic of binding to something specific, is insufficient to describe the genus. Further, given the highly diverse nature of antibodies, particularly in CDRs, even one of skill in the art cannot envision the structure of an antibody by only knowing its binding characteristics. Thus, the specification does not provide substantive evidence for possession of this large and variable genus, encompassing a potentially massive number of antibodies or antigen-binding fragments thereof claimed only by a partial structure and functional characteristics.
Additionally, the specification fails to disclose a representative number of species. Thus, the genus has substantial variation because of the numerous alternatives and combinations permitted. MPEP §2163 states that for a generic claim, the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. If the genus has a substantial variance (as in the instant case), the disclosure must describe a sufficient variety of species to reflect the variation within that genus. Although the MPEP does not define what constitutes a sufficient number of representative species, the courts have indicated what does not constitute a representative number to adequately describe a broad genus. The courts determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus (e.g. see In re Gostelli, 872, F.2d at 1012, 10 USPQ2d at 1618).
Further, the disclosure of only one or two species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]; emphasis added. "See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615; Noelle v. Lederman, 355 F.3d 1343, 1350, 69 USPQ2d 1508, 1514 (Fed. Cir. 2004) (Fed. Cir. 2004) "[A] patentee of a biotechnological invention cannot necessarily claim a genus after only describing a limited number of species because there may be unpredictability in the results obtained from species other than those specifically enumerated."). "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when ... the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed." In re Curtis, 354 F.3d 1347, 1358, 69 USPQ2d 1274, 1282 (Fed. Cir. 2004).
Accordingly, the specification also does not provide adequate written description to identify the broad genus of the claims, claimed only by a partial structure and functional characteristics and not structures per se, because inter alia, it does not describe a sufficient number and/or a sufficient variety of representative species to reflect the breadth and variation within the claimed genus. Consequently, based on the lack of information within the specification, there is evidence that a representative number and a representative variety of the numerous antibodies had not yet been identified and thus the specification represents little more than a wish for possession; See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406 (written description requirement not satisfied by merely providing "a result that one might achieve if one made that invention"); In re Wilder, 736 F.2d 1516,1521,222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming a rejection for lack of written description because the specification does "little more than outline goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate"). Therefore, one of skill in the art would not conclude that Applicant was in possession of the broad and highly variable genus of antibodies claimed only by a partial structure and functional characteristics.
In Abbvie v. Centocor (Fed. Cir. 2014), the Court held that a disclosure of many different antibodies was not enough to support the genus of all neutralizing antibodies because the disclosed antibodies were very closely related to each other in structure and were not representative of the full diversity of the genus. The Court further noted that functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support especially in technology fields that are highly unpredictable where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. The instant case has many similarities to AbbVie above. First, the claims clearly attempt to define the genus of antibody that binds to GDF-15 by a method of treating primary mitochondrial myopathy, the method comprising administering to a subject in need thereof a therapeutically effective amount of an isolated antibody that binds GDF-15. As noted by AbbVie above, functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description. Second, there is no information in the specification based upon which one of skill in the art would conclude that the disclosed species for which applicant has identified as having the recited functions would be representative of the entire genus. The specification discloses no structure to correlate with the function. Therefore, the specification provides insufficient written description to support the genus encompassed by the claim. Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, makes clear that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not "clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed." (See Vas-Cath at page 1116.)
Isolated antibody that binds to GDF-15 comprising fewer than six CDRs do not meet the requirements under 35 U.S.C. 112 first paragraph because the skilled artisan cannot envision the detailed chemical structure of the encompassed antibody variants, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. The nucleic acid and/or protein itself is required. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. In Fiddes v. Baird, 30 USPQ2d 1481, 1483, claims directed to mammalian FGF's were found unpatentable due to lack of written description for the broad class. The specification provided only the bovine sequence.
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that: ...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). 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." Lockwood, 107 F.3d at 1572, 41 USPQ2d 1966.
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. Paul (Fundamental Immunology, 3rd Edition, Raven Press, New York, Chapter 8, pages 292-295, 1993) teaches that the amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences, which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (See pages 293-295). While some publications acknowledge that CDR3 is important for antigen binding, the conformations of other CDRs as well as the framework are equally important in antigen binding. For example, MacCallum et al. (Journal of Molecular Biology, 262:732-745, 1996) analyzed antigen-contacting residues and combining site shape of various antibodies and state that although CDR3 of the heavy chain and light chain dominate, a number of residues outside of the standard CDR definitions make antigen contacts (See page 733) . MacCallum et al. teach that antigens tend to bind to the antibody residues located at the center of the combining site where the six CDRs meet (See abstract and page 742) and less central CDR residues are only contacted by large antigens (See page 733 and 735). MacCallum et al. further teach that non-contacting residues are important in defining "canonical" backbone conformations.
The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site, is further underscored by Casset et al. (Biochemical and Biophysical Research Communications, 307:198-205, 2003), which discuss the importance of multiple CDRs in antigen contact. Casset et al. teach that all antibodies have six CDR residues, all of which are more or less involved in antigen recognition (See page 199). Casset et al. teach that peptide mimetics of antibody combining sites have previously only targeted CDR H3, since this CDR is typically at the center of most, if not all, antigen interactions; however this strategy is flawed since other CDRs play an important role in the recognition of antigen (See page 199). Casset et al. construct a peptide mimetic of an anti-CD4 monoclonal antibody, containing antigen contact residues from five CDR regions, except L2 and additionally using a framework residue located just before the H3 and show that the peptide has high binding to CD4, thus signifying the contribution of multiple CDRs, and not a single CDR, in antigen recognition (See page 202 and Figure 4). Vajdos et al. (Journal of Molecular Biology, 2002 Jul 5;320(2):415-28) additionally states that, “ ... Even within the Fv, antigen binding is primarily mediated by the complementarity determining regions (CDRs), six hypervariable loops (three each in the heavy and light chains) which together present a large contiguous surface for potential antigen binding. Aside from the CDRs, the Fv also contains more highly conserved framework segments which connect the CDRs and are mainly involved in supporting the CDR loop conformations, although in some cases, framework residues also contact antigen. As an important step to understanding how a particular antibody functions, it would be very useful to assess the contributions of each CDR side-chain to antigen binding, and in so doing, to produce a functional map of the antigen-binding site.
Further, Sela-Culang et al. 2013 (The structural basis of antibody-antigen recognition; Frontiers in Immunology 4(302):1-13) teach the hypervariable loops within the variable domains of antibody polypeptides are widely assumed to be responsible for antigen recognition while the constant domains are believed to mediate effector activation, but that recent analysis indicates that their clear functional separation between the two regions is an over-simplification (see abstract). Sela-Culang et al. teach some residues within the CDRs may not participate in antigen binding and some residues outside the CDRs (e.g. in framework regions and in the constant domains) often contribute critically to the integration with the antigen (see abstract). Sela-Culang et al. teach understanding the role of each structural element is essential for successful engineering of binding polypeptides (e.g. page 2, left column). Sela-Culang et al. teach almost all of the residues predicted to be part of an epitope may be considered as correct predictors as they will bind to some antibodies but also are false predictors as they don’t bind to the others and accordingly that predicting that a residue is not in an epitope may be either a true negative or a false negative depending on the anybody considered (page 2, right column). Sela-Culang et al. teach each CDR has its own unique amino-acid composition different from the composition of the other CDRs and that each CDR has a unique set of contact preferences favoring certain amino acids over others (page 5-6, bridging). Sela-Culang et al. teach the combined action of all six CDRs is the evolutionary response of the immune system that enables the antibody polypeptide to recognize virtually any surface patch on the antigen (page 6). Therefore, the state of the art supports that even the skilled artisan requires guidance on the critical structures of the antibody per se and thereby does not provide adequate written description support for which structural features of any given polypeptide would predictably retain their functional activities.
Accordingly, one of skill in the art would conclude that the claimed invention encompasses a plurality of antibodies comprising fewer than six CDRs that may not have the biological functions recited in the claims. It should be noted that the claimed invention encompasses the antibody that binds GDF-15. Based on the teachings of the instant specification and the prior art, one of skill in the art would not conclude that Applicant was in possession of the claimed genus of antibodies.
Therefore, the species specifically disclosed are not representative of the genus because the genus is highly variant. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 USC 112 is severable from its enablement provision. (See page 1115).
Enablement - Biological Deposit
6. Claim 18 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
The claims are drawn to a method of treating primary mitochondrial myopathy (PMM), the method comprising administering to a subject in need thereof a therapeutically effective amount of an isolated antibody that binds to GDF-15. The dependent claim 18 is the method of claim 1, wherein the antibody, or antigen-binding fragment thereof, comprises the amino acid sequence encoded by the insert in the plasmid deposited at the ATCC and having ATCC Accession No. PTA-125038 and the amino acid sequence encoded by the insert in the plasmid deposited at the ATCC and having ATCC Accession No. PTA- 125039
The claims require a specific amino acid sequence encoded by the insert in the plasmid deposited under accession no. PTA-125038 and PTA- 125039 . It is unclear if the plasmid having the exact chemical identity of aforementioned clones is known and publicly available, or can be reproducibly isolated without undue experimentation. Therefore, a suitable deposit for patent purposes is suggested. Without a publicly available deposit of the above antibody, one of ordinary skill in the art could not be assured of the ability to practice the invention as claimed. Exact replication of: (1) the claimed antibody; (2) a cell line which produces the chemically and functionally distinct antibody claimed; and/or (3) the claimed antibody’s nucleic acid sequence is an unpredictable event.
For example, very different VH chains (about 50% homologous) can combine with the same VK chain to produce antibody-binding sites with nearly the same size, shape, antigen specificity, and affinity. A similar phenomenon can also occur when different VH sequences combine with different VK sequences to produce antibodies with very similar properties. The results indicate that divergent variable region sequences, both in and out of the complementarity-determining regions, can be folded to form similar binding site contours, which result in similar immunochemical characteristics. [FUNDAMENTAL IMMUNOLOGY 242 (William E. Paul, M.D. ed., 3d ed. 1993)]. Therefore, it would require undue experimentation to reproduce the claimed antibody.
The specification lacks deposit information for antibody clones deposited under accession no. PTA-125038 and PTA- 125039. It is unclear whether plasmids possessing the identical properties of the clones are known and publicly available or can be reproducibly isolated from nature without undue experimentation.
Exact replication of a cell line is an unpredictable event. Because one of ordinary skill in the art could not be assured of the ability to practice the invention as claimed in the absence of the availability of the claimed antibody clones deposited under accession no. PTA-125038 and PTA- 125039, a suitable deposit is required for patent purposes, evidence of public availability of the claimed antibody or evidence of the reproducibility without undue experimentation of the claimed plasmid, is required.
If the deposit of the antibodies is made under the provisions of the Budapest Treaty, filing of an affidavit or declaration by applicant or assignees or a statement by an attorney of record who has authority and control over the conditions of deposit over his or her signature and registration number stating that the deposit of antibodies has been accepted by an International Depository Authority under the provisions of the Budapest Treaty and that all restrictions upon public access to the deposited material will be irrevocably removed upon the grant of a patent on this application. This requirement is necessary when deposits are made under the provisions of the Budapest Treaty as the Treaty leaves this specific matter to the discretion of each State.
If the deposit of plasmid is not made under the provisions of the Budapest Treaty, then in order to certify that the deposit complies with the criteria set forth in 37 CFR 1.801-1.809 regarding availability and permanency of deposits, assurance of compliance is required. Such assurance may be in the form of an affidavit or declaration by applicants or assignees or in the form of a statement by an attorney of record who has the authority and control over the conditions of deposit over his or her signature and registration number averring:
(a) during the pendency of this application, access to the deposits will be afforded to the Commissioner upon request;
(b) all restrictions upon the availability to the public of the deposited biological material will be irrevocably removed upon the granting of a patent on this application;
(c) the deposits will be maintained in the public repository for a period of at least thirty years from the date of deposit or for the enforceable life of the patent of or for a period of five years after the date of the most recent request for the furnishing of a sample of the deposited biological material, whichever is longest; and
(d) the deposits will be replaced if they should become nonviable or non-replicable.
In addition, a deposit of biological material that is capable of self-replication either directly or indirectly must be viable at the time of deposit and during the term of deposit. Viability may be tested by the repository. The test must conclude only that the deposited material is capable of reproduction. A viability statement for each deposit of biological material not made under the Budapest Treaty must be filed in the application and must contain:
1) The name and address of the depository;
2) The name and address of the depositor;
3) The date of deposit;
4) The identity of the deposit and the accession number given by the depository;
5) The date of the viability test;
6) The procedures used to obtain a sample if test is not done by the depository; and
7) A statement that the deposit is capable of reproduction.
If a deposit is made after the effective filing date of the application for patent in the United States, a verified statement is required from a person in a position to corroborate that the biological material described in the specification as filed is the same as that deposited in the depository, stating that the deposited material is identical to the biological material described in the specification and was in the applicant's possession at the time the application was filed. See MPEP 2406 and 37 CFR 1.804(b).
Applicant's attention is directed to In re Lundak, 773 F.2d. 1216, 227 USPQ 90 (CAFC 1985) and 37 CFR 1.801-1.809 for further information concerning deposit practice
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
7. Claims 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Yatsuga, et al. Yatsuga, et al. (Yatsuga S, Fujita Y, Ishii A, Fukumoto Y, Arahata H, Kakuma T, Kojima T, Ito M, Tanaka M, Saiki R, Koga Y. Growth differentiation factor 15 as a useful biomarker for mitochondrial disorders. Ann Neurol. 2015 Nov;78(5):814-23. doi: 10.1002/ana.24506. Epub 2015 Oct 14. PMID: 26463265; PMCID: PMC5057301.) in view of Lerner, et al. (US 9,725,505 B2, issued 08/08/2017).
The instant claims are drawn to a method of treating primary mitochondrial myopathy, the method comprising administering to a subject in need thereof a therapeutically effective amount of an isolated antibody that binds to GDF-15.
Yatsuga teach a population of subjects having primary mitochondrial myopathy (PMM) disorders including MELAS, Leigh syndrome, and Kearns-Sayre syndrome (Participants section and table 2). Yatsuga teach the disorders are characterized by pathologically and markedly elevated circulating GDF-15, 6-fold over controls and non-overlapping with the control range (Abstract, Results and Figure 2) which correlated with disease severity (results section, paragraph 5 and figure 4). Yatsuga teach the population in which PMM is a condition of GDF-15 overexpression. Yatsuga further teach GDF-15 is currently under investigation as a marker of the clinical rick factors, mortality, morbidity and effectiveness treatments for heart disease, kidney disease, and some cancers (introduction suction). Yatsuga further teach GDF-15 may serve as a muse marker for PMM diagnosis and evaluation of therapeutic efficacy of drugs (introduction section).
Yatsuga does no teach administering an antibody that binds to GDF-15 to that population.
Lerner, et al. teach administering to a subject in need thereof a therapeutically effective amount of an isolated monoclonal antibody that binds and neutralized human GDF-15 to treat GDF-15 mediated conditions including cachexia and sarcopenia (detailed description section, first paragraph, column 7), demonstrating that administration of the antibody produces a gain of gastrocnemius muscle mass restored toward non-tumor bearing levels (Figure 29A-C, column 6).
It would have been obvious to one of ordinary skill in the art before the effective filing date to administering Lerner’s anti-GDF15 antibody to the PMM subject of Yatsuga. Yatsuga discloses the population with the disorder that PMM subjects have pathologically elevated GDF-15 and Lerner, et al. discloses a means of neutralizing GDF-15 that restores muscle. A skilled artisan would have been motivated to apply Lerner’s GDF-15 neutralizing therapy to Yatsuga’s GDF15 overexpression population. A rationale to support a conclusion that a claim would have been obvious is that all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded nothing more than predictable results to one of ordinary skill in the art. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395 (2007) (see MPEP §§ 2143, A. and 2143.02).
Yatsuga teaches MELAS as a PMM disorder that is correlated with elevated GDF-15 and additionally teaches Leigh Syndrome and Kearns-Sayre Syndrome, thus, reciting the limitation of instant claim 2. Lerner, et al. teach administration of the antibody allowed for gain of muscle mass and reversal of involuntary weight loss compared to before administration (figure 29A-C). Applying this to the PMM subject of Yatsuga yield improvement in one or more signs or symptoms of PMM relative to before administration, thus, reciting the limitation of instant claim 3. Lerner, et al characterizes the treated GDF-15 mediated condition by fatigue, weakness and loss of muscle mass (column 7, paragraph 3), thus the sign and symptoms improved comprise physical fatigue, muscle weakness and/or exercise intolerance, therefore, reciting the limitation of instant claim 4. Lerner, et al. treat sarcopenia, defined as loss of skeletal muscle mass and muscle strength (column 7, paragraph 4) and demonstrates a gain of gastrocnemius muscle mass and reverse of weight loss upon administration (figure 29A-C). The improvement therefore comprises increased body weight gain, increase lean/skeletal muscle and restored muscle strength, satisfying the limitation of instant claim 5. The combination of references is directed to the PMM population of Yatsuga, and Yatsuga analyzes cancer bearing and heart failure disease control separated from the PMM population in the same study. Thus, a PMM subject does not have cachexia, cancer and/or heart failure. The negative limitation recites an inherent characteristic of the population already targeted, thus, satisfying the limitation of instant claim 6. Yatsuga teaches that PMM subjects exhibit elevated GDF-15 in the untreated diagnostic cohort (results section, figure 2), therefore, the subject of the combination of references therefore has an elevated level and/or activity of GDF-15 before administering, which recites the limitation of instant claim 7. The combination of references renders obvious the method of instant claims 1-7.
8. Claims 8-21 are rejected under 35 U.S.C. 103 as being unpatentable over Yatsuga, et al. and Lerner, et al. as applied to claims 1-7 and in further view of Beaumont, et al. (US 2020/0055930 A1, published 02/20/2020).
Instant claims 8-21 teach the CDRs, heavy and light chain of the antibody that binds GDF-15 and dosages of administration.
The teachings of Yatsuga, et al. and Lerner, et al. are above.
Yatsuga, et al. and Lerner, et al. et al. do not teach the CDRs, heavy and light chain of the antibody that binds GDF-15 and dosages of administration.
However, Beaumont, et al. teach the antibody of instant claims 8, 9 and 10 (claim 1) which includes the six CDRs (instant SEQ ID NO: 95, 28, 9, 32, 165 and 52) as well as the heavy chains and light chains (instant SEQ ID NO: 166, 163, 164 and 162).
Instant SEQ ID NO: 95 is 100% identical to Beaumont SEQ ID NO: 95
Query Match 100.0%; Score 56; Length 11;
Best Local Similarity 100.0%;
Matches 11; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RTSQSVHNYLA 11
|||||||||||
Db 1 RTSQSVHNYLA 11
Instant SEQ ID NO: 28 is 100% identical to Beaumont SEQ ID NO: 28
Query Match 100.0%; Score 34; Length 7;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DASTRAD 7
|||||||
Db 1 DASTRAD 7
Instant SEQ ID NO: 9 is 100% identical to Beaumont SEQ ID NO: 9
Query Match 100.0%; Score 65; Length 9;
Best Local Similarity 100.0%;
Matches 9; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QQFWSWPWT 9
|||||||||
Db 1 QQFWSWPWT 9
Instant SEQ ID NO: 32 is 100% identical to Beaumont SEQ ID NO: 32
Query Match 100.0%; Score 55; Length 10;
Best Local Similarity 100.0%;
Matches 10; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GYTFSSYNID 10
||||||||||
Db 1 GYTFSSYNID 10
Instant SEQ ID NO: 165 is 100% identical to Beaumont SEQ ID NO: 165
Query Match 100.0%; Score 94; Length 17;
Best Local Similarity 100.0%;
Matches 17; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GINPIFGTAFYNQKFQG 17
|||||||||||||||||
Db 1 GINPIFGTAFYNQKFQG 17
Instant SEQ ID NO: 52 is 100% identical to Beaumont SEQ ID NO: 52
Query Match 100.0%; Score 56; Length 11;
Best Local Similarity 100.0%;
Matches 11; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EAITTVGAMDH 11
|||||||||||
Db 1 EAITTVGAMDH 11
Instant SEQ ID NO: 166 is 100% identical to Beaumont SEQ ID NO: 166
Query Match 100.0%; Score 625; Length 120;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSYNIDWVRQAPGQGLEWMGGINPIFGTAFY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSYNIDWVRQAPGQGLEWMGGINPIFGTAFY 60
Qy 61 NQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREAITTVGAMDHWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREAITTVGAMDHWGQGTLVTVSS 120
Instant SEQ ID NO: 163 is 100% identical to Beaumont SEQ ID NO: 163
Query Match 100.0%; Score 573; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPATLSLSPGERATLSCRTSQSVHNYLAWYQQKPGQAPRLLIYDASTRADGIPA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPATLSLSPGERATLSCRTSQSVHNYLAWYQQKPGQAPRLLIYDASTRADGIPA 60
Qy 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQFWSWPWTFGQGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQFWSWPWTFGQGTKVEIK 107
Instant SEQ ID NO: 164 is 100% identical to Beaumont SEQ ID NO: 164
Query Match 100.0%; Score 2385; Length 449;
Best Local Similarity 100.0%;
Matches 449; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSYNIDWVRQAPGQGLEWMGGINPIFGTAFY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSYNIDWVRQAPGQGLEWMGGINPIFGTAFY 60
Qy 61 NQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREAITTVGAMDHWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREAITTVGAMDHWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGA 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPG 449
|||||||||||||||||||||||||||||
Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPG 449
Instant SEQ ID NO: 162 is 100% identical to Beaumont SEQ ID NO: 162
Query Match 100.0%; Score 1126; Length 214;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPATLSLSPGERATLSCRTSQSVHNYLAWYQQKPGQAPRLLIYDASTRADGIPA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPATLSLSPGERATLSCRTSQSVHNYLAWYQQKPGQAPRLLIYDASTRADGIPA 60
Qy 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQFWSWPWTFGQGTKVEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQFWSWPWTFGQGTKVEIKRTVAAPSVFIFPP 120
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
It would have been obvious to use Beaumont’s anti-GDF15 antibody as the antibody administered in the method of Yatsuga and Lerner. The simple substitution of one known element for another is likely to be obvious when predictable results are achieved. See KSR International Co. v. Teleflex Inc., 550 U.S. 398, 415-421, USPQ2d 1385, 1395 – 97 (2007) (see MPEP § 2143, B.).
Beaumont teach subcutaneous and intravenous administration of the antibody (E122 and E123), thus, reciting the limitation of instant claim 11 and 12. Beaumont teach administration about twice a week, once a week, once every two weeks, once every three weeks, once every four weeks, once every five weeks, once every six weeks, once every seven weeks, once every eight weeks, once every nine weeks, once every ten weeks, twice a month, once a month, once every two months, once every three months, or once every four months once every five months, once every six months, once every seven months, once every eight months, once every nine months, once every ten months, once every eleven months or once every twelve months (E124), thus, reciting the limitation of instant claim 13. Beaumont teach once a week administration at a dose between 0.1 mg and about 1000 mg (E124-127), thus, reciting the limitations of instant claim 14 and 15. Beaumont teach administration once every two weeks at a dose between 0.1 mg and about 130 mg (E128-130), thus, reciting the limitation of instant claim 16. Beaumont teach administration four weeks a dose between about 0.1 mg and about 400 mg (E131-133), thus reciting the limitation of instant claim 17. Beaumont teach that the antibody is encoded by the inserts of the plasmids deposited at the ATCC under Accession Nos: PTA-125038 and PTA-125039 (claim 1 and E43-46).
Claim 19-21 in view of Yatsuga, Lerner and Beaumont is rendered obvious for the same reasons for above.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
9. Claims 8-10, 18-21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,566,066 (issued 01/31/2023) in view of
The instant claims are drawn to a method of treating primary mitochondrial myopathy, the method comprising administering to a subject in need thereof a therapeutically effective amount of an isolated antibody that binds to GDF-15.
U.S. Patent No. 066’ teach the antibody that binds to GDF-15. The antibody is 100% identical to the instant antibody which includes the six CDRs (instant SEQ ID NO: 95, 28, 9, 32, 165 and 52) as well as the heavy chains and light chains (instant SEQ ID NO: 166, 163, 164 and 162) (claim 1).
Instant SEQ ID NO: 95 is 100% identical to U.S. Patent No. 066’ SEQ ID NO: 95
Query Match 100.0%; Score 56; Length 11;
Best Local Similarity 100.0%;
Matches 11; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 RTSQSVHNYLA 11
|||||||||||
Db 1 RTSQSVHNYLA 11
Instant SEQ ID NO: 28 is 100% identical to U.S. Patent No. 066’ SEQ ID NO: 28
Query Match 100.0%; Score 34; Length 7;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DASTRAD 7
|||||||
Db 1 DASTRAD 7
Instant SEQ ID NO: 9 is 100% identical to U.S. Patent No. 066’ SEQ ID NO: 9
Query Match 100.0%; Score 65; Length 9;
Best Local Similarity 100.0%;
Matches 9; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QQFWSWPWT 9
|||||||||
Db 1 QQFWSWPWT 9
Instant SEQ ID NO: 32 is 100% identical to U.S. Patent No. 066’ SEQ ID NO: 32
Query Match 100.0%; Score 55; Length 10;
Best Local Similarity 100.0%;
Matches 10; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GYTFSSYNID 10
||||||||||
Db 1 GYTFSSYNID 10
Instant SEQ ID NO: 165 is 100% identical to U.S. Patent No. 066’ SEQ ID NO: 165
Query Match 100.0%; Score 94; Length 17;
Best Local Similarity 100.0%;
Matches 17; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GINPIFGTAFYNQKFQG 17
|||||||||||||||||
Db 1 GINPIFGTAFYNQKFQG 17
Instant SEQ ID NO: 52 is 100% identical to U.S. Patent No. 066’ SEQ ID NO: 52
Query Match 100.0%; Score 56; Length 11;
Best Local Similarity 100.0%;
Matches 11; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EAITTVGAMDH 11
|||||||||||
Db 1 EAITTVGAMDH 11
Instant SEQ ID NO: 166 is 100% identical to U.S. Patent No. 066’ SEQ ID NO: 166
Query Match 100.0%; Score 625; Length 120;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSYNIDWVRQAPGQGLEWMGGINPIFGTAFY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSYNIDWVRQAPGQGLEWMGGINPIFGTAFY 60
Qy 61 NQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREAITTVGAMDHWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREAITTVGAMDHWGQGTLVTVSS 120
Instant SEQ ID NO: 163 is 100% identical to U.S. Patent No. 066’ SEQ ID NO: 163
Query Match 100.0%; Score 573; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPATLSLSPGERATLSCRTSQSVHNYLAWYQQKPGQAPRLLIYDASTRADGIPA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPATLSLSPGERATLSCRTSQSVHNYLAWYQQKPGQAPRLLIYDASTRADGIPA 60
Qy 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQFWSWPWTFGQGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQFWSWPWTFGQGTKVEIK 107
Instant SEQ ID NO: 164 is 100% identical to U.S. Patent No. 066’ SEQ ID NO: 164
Query Match 100.0%; Score 2385; Length 449;
Best Local Similarity 100.0%;
Matches 449; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSYNIDWVRQAPGQGLEWMGGINPIFGTAFY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGSSVKVSCKASGYTFSSYNIDWVRQAPGQGLEWMGGINPIFGTAFY 60
Qy 61 NQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREAITTVGAMDHWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQKFQGRVTITADESTSTAYMELSSLRSEDTAVYYCAREAITTVGAMDHWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPEAAGA 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPG 449
|||||||||||||||||||||||||||||
Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPG 449
Instant SEQ ID NO: 162 is 100% identical to U.S. Patent No. 066’ SEQ ID NO: 162
Query Match 100.0%; Score 1126; Length 214;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPATLSLSPGERATLSCRTSQSVHNYLAWYQQKPGQAPRLLIYDASTRADGIPA 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPATLSLSPGERATLSCRTSQSVHNYLAWYQQKPGQAPRLLIYDASTRADGIPA 60
Qy 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQFWSWPWTFGQGTKVEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLEPEDFAVYYCQQFWSWPWTFGQGTKVEIKRTVAAPSVFIFPP 120
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
U.S. Patent No. 066’ teach the amino acid sequence encoded by the insert of the plasmid deposited at the ATCC and having ATCC Accession No. PTA-125038, and the amino acid sequence encoded by the insert of the plasmid deposited at the ATCC and having ATCC Accession No. PTA-125039 (claim 1). This recites the antibody of instant claim 8, 9, 10, 18, 20, and 21.
U.S. Patent No. 066’ does not teach the method of treating primary mitochondrial myopathy, comprising administering to a subject the antibody that binds to GDF-15.
However, Yatsuga teach a population of subjects having primary mitochondrial myopathy (PMM) disorders including MELAS, Leigh syndrome, and Kearns-Sayre syndrome (Participants section and table 2). Yatsuga teach the disorders are characterized by pathologically and markedly elevated circulating GDF-15, 6-fold over controls and non-overlapping with the control range (Abstract, Results and Figure 2) which correlated with disease severity (results section, paragraph 5 and figure 4). Yatsuga teach the population in which PMM is a condition of GDF-15 overexpression. Yatsuga further teach GDF-15 is currently under investigation as a marker of the clinical rick factors, mortality, morbidity and effectiveness treatments for heart disease, kidney disease, and some cancers (introduction suction). Yatsuga further teach GDF-15 may serve as a muse marker for PMM diagnosis and evaluation of therapeutic efficacy of drugs (introduction section). Lerner, et al. teach administering to a subject in need thereof a therapeutically effective amount of an isolated monoclonal antibody that binds and neutralized human GDF-15 to treat GDF-15 mediated conditions including cachexia and sarcopenia (detailed description section, first paragraph, column 7), demonstrating that administration of the antibody produces a gain of gastrocnemius muscle mass restored toward non-tumor bearing levels (Figure 29A-C, column 6).
It would have been obvious to one of ordinary skill in the art to administer the anti-GDF15 antibody claimed in U.S. Patent No. 066’ in a method of treating the PMM population of Yatsuga because Yatsuga identified PMM as a GDF15 overexpression population in need of treatment directed at elevated GDF-15 and Lerner teaches that neutralizing the GDF-15 with the anti-GDF15 antibody treats the GDF-15 muscle wasting and restores muscle. One of ordinary skill in the art would have been motivated to use the antibody claimed in U.S. Patent No. 066’ for neutralizing pathologically elevated GDF-15 to restore muscle taught by Lerner, in the PMM population taught by Yatsuga.
Conclusion
10. No claims are allowed
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Syed J Abbas whose telephone number is (571)272-0015. The examiner can normally be reached M-Th, 9:00AM-4:00PM.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Vanessa Ford can be reached at 571-272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SYED J ABBAS/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
Prosecution Insights