DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s election without traverse of Group I in the reply filed on 5/6/25 is acknowledged.
Claim Status
The claim set filed 6/11/25 is acknowledged. Claims 13, 16-17, 27, and 31 are cancelled. New claims 45-47 are added. Claims 1-12, 14-15, 18-26, 28-30, and 32-47 are pending. Claims 19, 22-26, 28-30, and 32-44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 5/6/25.
Claims 1-12, 14-15, 18, 20-21, and 45-47 are currently under consideration for patentability under 37 CFR 1.104.
Information Disclosure Statement
The information disclosure statements filed on 2/23/23, 7/31/23, 5/24/24, and 6/11/24 have been considered. Signed copies are enclosed. The references lined through were not considered because a copy of the reference was not provided (see 37 CFR 1.98(a)).
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Notice to Comply with 37 CFR §§ 1.821—1.825
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 C.F.R. §§ 1.821-1.825 for the following reason(s):
The sequence listing recites SEQ ID NO:13, 14, 29, 30, 45, 46, 61, 62, 77, 78, 93, 94, 149, 150, 213, 214, and 223, but no sequences appear in the listing for these SEQ ID NOs.
Claim 15 recites SEQ ID NO:150, which has no sequence in the listing.
To be considered fully responsive, any reply to this action must address these deficiencies, as this requirement will not be held in abeyance.
Claim Objections
Claim 21 is objected to because of the following informalities: the phrase “wherein GDF8” should be amended to read “wherein the GDF8”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 20-21 and 45 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 MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention.”
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicants were in possession of the claimed genus.
The instant claims are directed to an isolated antibody or antigen binding fragment thereof that binds to Activin A, which comprises the CDRs of an HCVR and LCVR having the sequences of SEQ ID NO:138 or 146. The claims name various functions for the antibody, including reciting a specific Kd, Ka, binding to Activin A, blocking binding of Activin A, blocking activation of Activin A receptor, and competing with reference antibodies where the antibody may bind to the same, unidentified, epitope. The CDRs of HCVR and LCVR 38/146 are disclosed as possibly including SEQ ID NOs: 140, 142, 144, and 148, 150, and 152, respectively. The Activin A antibody is adequately described. However, the antibody or fragment can be included in a pharmaceutical composition with a GDF8 antagonist that is not adequately described.
The rejected claims are directed to a pharmaceutical composition that comprises a GDF8 antagonist, which can include a small molecule, nucleic acid, protein, antibody or antigen binding fragment thereof or any other molecule type. Therefore the claims encompass a wide range of agents with specific functions without either identifying the structure/function correlation or a representative number of species for the functional proteins. The encompassed genus of agents is unpredictable in their ability to perform specific functions. Except in claims 46 and 47, Applicant has not provided structure that correlates with the functions of being a GDF8 antagonist, or a representative number of species that would provide adequate description of the antagonist genus. A single anti-GDF8 antibody is presented in claims 46 and 47, but the claimed genus is not limited to this species.
The recited GDF8 antagonists have no correlation between their structure and function. The claims require that the antagonist exhibit a specific function, but the specification provides no guidance regarding which agents are capable of the required 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.)
With the exception of the antibody described in instant claims 46 and 47, the skilled artisan cannot envision the detailed chemical structure of the encompassed polypeptides, 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.
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 USPQ2datl966.
Regarding the encompassed antagonist proteins, protein chemistry is one of the most unpredictable areas of biotechnology. This unpredictability prevents prediction of the effects that a given number or location of mutations will have on a protein. As taught by Skolnick et al (Trends Biotechnol. 2000 Jan;18(1):34-9), sequence based methods for predicting protein function are inadequate because of the multifunctional nature of proteins (see e.g. abstract). Further, just knowing the structure of the protein is also insufficient for prediction of functional sites (see e.g. abstract). Sequence to function methods cannot specifically identify complexities for proteins, such as gain and loss of function during evolution, or multiple functions possible within a cells (see e.g. page 34, right column). Skolnick advocates determining the structure of the protein, then identifying the functionally important residues since using the chemical structure to identify functional sites is more in line with how a protein actually works (see e.g. page 34, right column).
The sensitivity of proteins to alterations of even a single amino acid in a sequence are exemplified by Burgess et al. (J. Cell Biol. 111:2129-2138, 1990) who teach that replacement of a single lysine reside at position 118 of acidic fibroblast growth factor by glutamic acid led to the substantial loss of heparin binding, receptor binding and biological activity of the protein and by Lazar et al. (Mol. Cell. Biol., 8:1247-1252, 1988) who teach that in transforming growth factor alpha, replacement of aspartic acid at position 47 with alanine or asparagine did not affect biological activity while replacement with serine or glutamic acid sharply reduced the biological activity of the mitogen. These references demonstrate that even a single amino acid substitution will often dramatically affect the biological activity and characteristics of a protein.
Further, Miosge (Proc Natl Acad Sci U S A. 2015 Sep 15;112(37):E5189-98) teach that Short of mutational studies of all possible amino acid substitutions for a protein, coupled with comprehensive
functional assays, the sheer number and diversity of missense mutations that are possible for proteins means that their functional importance must presently be addressed primarily by computational inference (see e.g. page E5189, left column). However, in a study examining some of these methods, Miosge shows that there is potential for incorrect calling of mutations (see e.g. page E5196, left column, top paragraph). The authors conclude that the discordance between predicted and actual effect of missense mutations creates the potential for many false conclusions in clinical settings where sequencing is performed to detect disease-causing mutations (see e.g. page E5195, right column, last paragraph). The findings in their study show underscore the importance of interpreting variation by direct experimental measurement of the consequences of a candidate mutation, using as sensitive and specific an assay as possible (see e.g. page E5197, left column, top paragraph). Additionally, Bork (Genome Research, 2000,10:398-400) clearly teaches the pitfalls associated with comparative sequence analysis for predicting protein function because of the known error margins for high-throughput computational methods. Bork specifically teaches that computational sequence analysis is far from perfect, despite the fact that sequencing itself is highly automated and accurate (p. 398, column 1). One of the reasons for the inaccuracy is that the quality of data in public sequence databases is still insufficient. This is particularly true for data on protein function. Protein function is context dependent, and both molecular and cellular aspects have to be considered (p. 398, column 2). Conclusions from the comparison analysis are often stretched with regard to protein products (p. 398, column 3). Further, although gene annotation via sequence database searches is already a routine job, even here the error rate is considerable (p. 399, column 2). Most features predicted with an accuracy of greater than 70% are of structural nature and, at best, only indirectly imply a certain functionality (see legend for table 1, page 399). As more sequences are added and as errors accumulate and propagate it becomes more difficult to infer correct function from the many possibilities revealed by database search (p. 399, paragraph bridging columns 2 and 3). The reference finally cautions that although the current methods seem to capture important features and explain general trends, 30% of those features are missing or predicted wrongly. This has to be kept in mind when processing the results further (p. 400, paragraph bridging cols 1 and 2).
Given the teachings of these references that point out the limitations and pitfalls of using sequence to predict functions, and the lack of a representative number of species across the breadth of the genus, one of skill in the art would reasonably conclude that Applicant has not met the written description provision of 35 USC 112(a) by broadly claiming a genus without providing either structure that correlates with function or a representative number of species of fusion proteins within the GDF8 antagonist genus.
The functional characteristics of antibodies (including binding specificity and affinity are dictated on their structure. Amino acid sequence and conformation 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. For example, Vajdos et al. (J Mol Biol. 2002 Jul 5;320(2):415-28 at 416) teaches 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." The art shows an unpredictable effect when making single versus multiple changes to any given CDR. For example, Brown et al. (J Immunol. 1996 May;156(9):3285-91 at 3290 and Tables 1 and 2), describes how the VH CDR2 of a particular antibody was generally tolerant of single amino acid changes, however the antibody lost binding upon introduction of two amino changes in the same region. The specification discloses one species within the instant claims scope and does not provide any guidance as to which amino acids can be varied while retaining the appropriate affinity or ability to bind/block Activin, or any of the other required functions.
Recently, the U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself even when preparation of such an antibody would be routine and conventional. Amgen, 872 F.3d at 1378-79. A key role played by the written description requirement is to prevent “attempt[s] to preempt the future before it has arrived.” Ariad at 1353, (quoting Fiers v. Revel, 984 F.2d at 1171). Upholding a patent drawn to a genus of antibodies that includes members not previously characterized or described could negatively impact the future development of species within the claimed genus of antibodies. In the instant application, neither the art nor the specification provide a sufficient representative number of antibodies or a sufficient structure-function correlation to meet the written description requirements.
Regarding nucleic acid based therapeutics, the efficacy of any possible DNA or RNA based therapeutic modality is highly unpredictable. This unpredictability stems from an inability to predict the effects of any particular sequence the expression or function of any target. As taught by Aagaard et al (Advanced Drug Delivery Reviews 59 (2007) 75–86), the development of RNAi based therapeutics faces several challenges, including the need for controllable or moderate promoter systems and therapeutics that are efficient at low doses (see page 79), the ability of an unpredictable number of sequences to stimulate immune responses, such as type I interferon responses (see page 79), competition with cellular RNAi components (see page 83), the side effect of suppressing off targets (see page 80), and challenging delivery (see page 83). The success of antisense strategies, including anti-RNA and anti-DNA strategies are also highly unpredictable. Warzocha et al (Leukemia and Lymphoma (1997) Vol. 24. pp. 267-281) teach that the efficacy of antisense effects varies between different targeted sites of RNA molecules and three dimensional RNA structures (see page 269), while DNA-targeting strategies have numerous problems including a restricted number of DNA sequences that can form triple helices at appropriate positions within genes and the inaccessibility of particular sequences due to histones and other proteins (see page 269). These references demonstrate that variation in RNA or DNA based therapeutics will often dramatically affect the biological activity and characteristics of the intended therapeutic. McKeague et al (J Nucleic Acids. 2012;2012:748913. Epub 2012 Oct 24) teach that aptamers have particular challenges because unlike antibodies or molecular imprinted polymers, their tertiary structure is highly dependent on solution conditions and they are easily degraded in blood. Further, they have less chemical diversity than other antagonist molecules (see page 2), and have issues associated with determining the Kd measurements for a given molecule (see page 13). Given the teachings of Aagaard et al, Warzocha et al, and McKeague et al, the claimed nucleic acid therapeutics could not be predicted based on the targets selected or similarities to the disclosed example therapeutics. Therefore, it is impossible for one of skill in the art to predict that any particular encompassed nucleic acid based therapeutic, such as oligonucleotide aptamers, RNAi molecules and antisense oligonucleotides, would function to decrease expression or function of a target gene or protein, or treat disease.
Regarding small molecule inhibitors of a particular protein target, the prediction of binding to a target, much less the inhibitory activity, is highly unpredictable. According to Guido et al (Curr Med Chem. 2008;15(1):37-46), accurately predicting the binding affinity of new drug candidates remains a major challenge in drug discovery (see page 37). There are a vast number of possible compounds that may bind a given target protein, many of which have likely not been discovered. Relying on virtual screening also lends unpredictability to the art regarding identification of molecules that would be capable of the required functions of the instant claims. Guido et al teach that there are two main complex issues with predicting activity for a small molecule: accurate structural modeling and/or correct prediction of activity (see page 40). As taught by Clark et al (J. Med. Chem., 2014, 57 (12), pp 5023–5038), even when guided by structural data, developing selective structure-activity relationships has been challenging owing to the similarities of the enzymes (see page 5028). Therefore, it is impossible for one of skill in the art to predict that any particular encompassed small molecule therapeutic would function to inhibit a particular protein, especially a particular protein family member, or treat disease.
MPEP § 2163.02 states, “[a]n objective standard for determining compliance with the written description requirement is, 'does the description clearly allow person of ordinary skill in the art to recognize that he or she invented what is claimed’”. The courts have decided: the purpose of the "written description" requirement is broader than to merely explain how to "make and use"; the 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 Vas-Cath, Inc v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991).
Furthermore, the written description provision of 35 USC §112 is severable from its enablement provision; and 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. Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993). And Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. Moreover, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has the Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed.
Therefore for all these reasons the specification lacks adequate written description, and one of skill in the art cannot reasonably conclude that Applicant had possession of the claimed invention at the time the instant application was filed.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 1-12, 18, 20-21, and 45-47 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 46 require CDRs from heavy and light chain sequences without actually setting forth the CDR sequences. There are two sets of CDRs referenced in claims 46 and 47, those for the GDF8 antagonists, for which claim 47 provides adequate description, and the CDRs for the antibody that binds Activin A, which is required by all of the rejected claims. There are several well established methods to determine CDRs. Using common methods to identify the CDRs produces variable CDR sequences. For example, numbering by the Chothia method produces a different CDR sequence than the Kabat method. Therefore, the methods do not name the same CDRs, and one of skill in the art would not know which of these embodiments would meet the requirements of the claims. The differences in CDRs may have different affinities or other functional characteristics that would not be capable of the required functions.
The term “significantly” in claim 6 is a relative term which renders the claim indefinite. The term “significantly” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 15 recites “SEQ ID NO:150”. However, the sequence listing for the application does not contain any sequence for SEQ ID NO:150. Therefore the scope of the encompassed CDR is indefinite.
The dependent claims do not remedy the deficiencies listed above and therefore are also rejected.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-12, 14-15, 18, 20-21, and 45-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-50 of copending Application No. 19/216,288 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are directed to an isolated antibody or antigen binding fragment thereof that binds to Activin A, which comprises the CDRs of an HCVR and LCVR having the sequences of SEQ ID NO:138 and 146, respectively. The claims name various functions for the antibody, including reciting a specific Kd, Ka, binding to Activin A, blocking binding of Activin A, blocking activation of Activin A receptor, and competing with reference antibodies where the antibody may bind to the same, unidentified, epitope. The CDRs of HCVR and LCVR 138/146 are disclosed as SEQ ID NOs: 140, 142, and 144, and 148, 150, and 152, respectively. The antibody or fragment can be included in a pharmaceutical composition with a GDF8 antagonist and pharmaceutically acceptable carrier.
The reference patent claims are directed to a method of preventing or treating a cardiac dysfunction or heart failure in a subject comprising administering an activin A antagonist (see e.g. claim 1). The antagonist can be an antibody or antigen binding fragment (see e.g. claim 2). The Kd and Ka can be the same for the antibody or antigen binding fragment (see e.g. claims 3-5). The antibody or fragment thereof can have the same activin receptor blocking activities (see e.g. claims 6-11), and can inhibit SMAD complex signaling (see e.g. claim 12). The Antibody can have the CDRs of an HCVR and LCVR of SEQ ID NO:138 and 146 (see e.g. claims 13 and 14), or comprise HCVR and LCVR of SEQ ID NO:138 and 146 (see e.g. claims 16 and 17), which are identical to instant SEQ ID NO:138 and 146, respectively. The CDRs can comprise SEQ ID NO:140-142-144-148-150-152, which are identical to the sequences of the same SEQ ID NO in the instant application (see e.g. claim 15). The antibody can be in a composition comprising a GDF8 antagonist, the sequences of which are shown in SEQ ID NO that are identical to the instant SEQ ID NO of the same number (see e.g. claims 25-30).
The instant claims differ from the reference claims because the instant claims are directed to an activin A antibody product genus, while the reference claims are directed to methods of using the antibody for treating disease.
The Federal Circuit held in Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010) that claims of a later patent can be held invalid for obviousness-type double patenting where an earlier patent claimed a compound, disclosing its utility in the specification, and a later patent claimed a method of using the compound for a use described in the specification of the earlier patent. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385-86. In this case, U.S. 4,808,614 (‘614) patent claimed gemcitabine and methods of using gemcitabine for treating viral infections. The patent also disclosed (but did not claim) using these compounds to fight cancer. U.S. 5,464,826 (‘826) patent claimed methods of using gemcitabine for treating cancer. The Federal Circuit found that “The asserted claims of the later '826 patent simply claim the anticancer use disclosed in the specification of the '614 patent as a method of use claim. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385. Therefore, we affirm the district court's judgment that the asserted claims, claims 2, 6, and 7, of the '826 patent are invalid for obviousness-type double patenting over the '614 patent.” Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010). This is similar to the instant application, which merely claims a product that is identical to the product used in the method of the copending application. For example, the instant specification states that the antibody of the instant claims can be used for preventing or treating heart failure (see e.g. paragraph [0036] of the instant specification). The copending specification explicitly recites the use of the product, which is identical to the antibody of the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-12, 14-15, 18, 20-21, and 45-47 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-46 of copending Application No. 19/251,109 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
The instant claims are directed to an isolated antibody or antigen binding fragment thereof that binds to Activin A, which comprises the CDRs of an HCVR and LCVR having the sequences of SEQ ID NO:138 and 146, respectively. The claims name various functions for the antibody, including reciting a specific Kd, Ka, binding to Activin A, blocking binding of Activin A, blocking activation of Activin A receptor, and competing with reference antibodies where the antibody may bind to the same, unidentified, epitope. The CDRs of HCVR and LCVR 138/146 are disclosed as SEQ ID NOs: 140, 142, and 144, and 148, 150, and 152, respectively. The antibody or fragment can be included in a pharmaceutical composition with a GDF8 antagonist and pharmaceutically acceptable carrier.
The reference patent claims are directed to an isolated antigen binding molecule comprising a binding domain that binds to GDF8 and a second antigen binding molecule that binds to Actvin A (see e.g. claim 1) and a method of preventing or treating a cardiac dysfunction or heart failure in a subject comprising administering an activin A antagonist (see e.g. claim 1). The antagonist can be an antibody or antigen binding fragment (see e.g. claim 2). The Kd and Ka can be the same for the antibody or antigen binding fragment (see e.g. claims 3-5). The antibody or fragment thereof can have the same activin receptor blocking activities (see e.g. claims 6-10), and can inhibit SMAD complex signaling (see e.g. claim 10). The Antibody can have the CDRs of an HCVR of SEQ ID NO:10, which is identical to instant SEQ ID NO:138 (see e.g. claim 18). The heavy chain can comprise SEQ ID NO:28, which includes the sequence of instant SEQ ID NO:146 (see e.g. claim 27). Therefore, the copending claims recite the same CDRs as the instant claims. The antibody can be in a composition comprising a GDF8 antagonist, the sequences of which are shown in Table 1 and are identical to the instant claims (see e.g. claims 15-17, 24-25, 29-32).
The instant claims differ from the reference claims because the reference claims are directed to a genus of antibodies, rather than specific antibodies with specific CDRs, as recited in the instant claims. The specifically named antibodies of the copending application include the sequences of the instant antibodies, along with other sequences that are not recited in the instant claims. Further, the reference claims are directed to methods of using the antibody for treating disease.
The Federal Circuit held in Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010) that claims of a later patent can be held invalid for obviousness-type double patenting where an earlier patent claimed a compound, disclosing its utility in the specification, and a later patent claimed a method of using the compound for a use described in the specification of the earlier patent. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385-86. In this case, U.S. 4,808,614 (‘614) patent claimed gemcitabine and methods of using gemcitabine for treating viral infections. The patent also disclosed (but did not claim) using these compounds to fight cancer. U.S. 5,464,826 (‘826) patent claimed methods of using gemcitabine for treating cancer. The Federal Circuit found that “The asserted claims of the later '826 patent simply claim the anticancer use disclosed in the specification of the '614 patent as a method of use claim. See Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385. Therefore, we affirm the district court's judgment that the asserted claims, claims 2, 6, and 7, of the '826 patent are invalid for obviousness-type double patenting over the '614 patent.” Sun Pharmaceutical Industries v. Eli Lilly and Co., 611 F.3d 1381, 1389 (2010). This is similar to the instant application, which merely claims a product that is identical to the product used in the method of the copending application. For example, the instant specification states that the antibody of the instant claims can be used for preventing or treating heart failure (see e.g. paragraph [0036] of the instant specification). The copending specification explicitly recites the use of the product, which is identical to the antibody of the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDREA MCCOLLUM whose telephone number is (571)272-4002. The examiner can normally be reached 9:00 AM to 6:00 PM EST.
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 on (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.
/ANDREA K MCCOLLUM/Examiner, Art Unit 1674