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 .
Status of Application, Amendments and/or Claims
The amendment of 18 May 2026 has been entered in full. Claims 1 and 21 are amended. Claims 7-11 and 20 are cancelled.
Claims 1-6, 12-19, 21, and 22 are pending.
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-6, 11-19, 21, and 22, drawn to a method of treating a subject that has cardiovascular disease or systemic sclerosis comprising treating the subject with an IgG3 β1-Adrenergic receptor antibody (or nucleic acid encoding such) in the reply filed on 18 May 2026 is acknowledged.
Claims 1-6, 12-19, 21, and 22 are under consideration in the instant application as they read upon the elected invention.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 31 December 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
1. Claims 15 and 21 are objected to because of the following informalities:
1a. In claim 15, line 1, the plural “vectors” should recite the singular, “vector” for consistency with claim 1.
1b. In claim 21, line 12 (subpart (b)(ii)), the phrase “treating said subject with” is missing and should be inserted before “a vector” (see subpart (a)(i), for example).
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.
2. Claims 1-6, 12-19, 21, and 22 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.
Claim 1 of the instant application is directed to a method of treating a subject that has cardiovascular disease (CVD), or Systemic Sclerosis (DD), comprising: treating a subject that has CVD or SS with at least one of the following:
(a) IgG3 β1-Adrenergic Receptor antibodies (IgG3 β1AR antibodies) or antigen-binding portion thereof; or
(b) a vector comprising a nucleic acid sequence encoding: i) said IgG3 β1AR antibodies, or ii) antigen-binding portion thereof.
Instant claim 21 recites a method comprising: (a) receiving results of, or conducting, an IgG3 β1-Adrenergic Receptor antibodies (IgG3 β1AR antibodies) level analysis on a sample from a subject with cardiovascular disease (CVD) or Systemic Sclerosis (SS), and (b) performing at least one of the following after identifying said sample as having higher levels of said IgG3 β1AR antibodies compared to control levels, i) treating said subject with IgG3 β1AR antibodies or antigen-binding portion thereof; and/or ii) vector comprising a nucleic acid sequence encoding: i) said IgG3 β1AR antibodies, or ii) said antigen-binding portion thereof.
The specification of the instant application teaches that the invention relates to systems, kits, and methods for treating a subject that has cardiovascular disease or Systemic Sclerosis with at least one of the following: a) IgG3 β1-Adrenergic Receptor antibodies (IgG3 β1AR antibodies), or antigen-binding portion thereof (e.g., derived from the subject themselves or other donor); or b) a vector comprising a nucleic acid sequence encoding the antigenic protein or IgG3 β1AR antibodies (page 11, lines 27-32). The specification discloses that IgG3 β1AR antibodies (and antigen-binding portions thereof) may be generated using various immunogens, such as all or a portion of SEQ ID NO:1 (e.g., the 26 amino acid SEQ ID NO: 2) (page 12, lines 14-17). The specification also generally discusses procedures for producing polyclonal, human, monoclonal, chimeric, humanized antibodies, (page 12, lines 21-33 through page 15, lines 1-14). Example 1 of the specification discloses purified IgG3(+) autoantibodies from patients (page 16; see also page 20).
However, the instant claims only recite treating a subject with IgG3 β1AR antibodies (or a vector comprising a nucleic acid sequence encoding such). The teachings of the specification are not adequate written description of an entire genus of IgG3 β1AR antibodies (or nucleic acids encoding such) that treat cardiovascular disease or Systemic Sclerosis.
The first paragraph of 35 U.S.C. § 112 "requires a 'written description of the invention' which is separate and distinct from the enablement requirement." Vas-Cath Inc. v. Mahurkar, 935 F.2d 1555, 1563 (Fed. Cir. 1991). An adequate written description of a chemical invention "requires a precise definition, such as by structure, formula, chemical name, or physical properties." University of Rochester v. G.D. Searle & Co., Inc., 358 F.3d 916, 927 (Fed. Cir. 2004); Regents of the Univ. of Cal. v. Eli Lilly & Co., Inc., 119 F.3d 1559, 1566 (Fed. Cir. 1997); Fiers v. Revel, 984 F.2d 1164, 1171 (Fed. Cir. 1993). "A description of what a material does, rather than of what it is, usually does not suffice." Rochester, 358 F.3d at 923; Eli Lilly, 119 F.3d at 1568. Instead, the "disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described." Id. In addition, possession of a genus "may be achieved by means of a recitation of a representative number of [compounds]... falling within the scope of the genus." Eli Lilly, 119 F.3d at 1569. Possession may not be shown by merely describing how to obtain possession of members of the claimed genus. See Rochester, 358 F.3d at 927.
Thus, case law dictates that to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include actual reduction to practice, disclosure of drawings or structure chemical formulas, sufficient relevant identifying characteristics (such as, complete or partial structure, physical and/or chemical properties, and functional characteristics when coupled with a known or disclosed structure/function correlation), methods of making the claimed product, level of skill and knowledge in the art, predictability in the art, or any combination thereof. In the instant case, the only factors present in the method claims are (i) a structural characteristic of IgG3 β1AR antibodies (and nucleic acids encoding such) and (ii) functional characteristics of recognizing/binding to β1AR and treating cardiovascular disease or Systemic Sclerosis. There is no other identification of any particular sequence or structure of the antibody (or nucleic acids) in the instant claims. There is also no identification of any particular sequence or structure that must be conserved in order to provide the required functions of recognizing/binding to β1AR and treating cardiovascular disease or Systemic Sclerosis. Thus, the claims are drawn to a genus of IgG3 antibodies (and nucleic acids encoding such) that (i) recognize and bind to β1AR and (ii) treat cardiovascular disease or Systemic Sclerosis.
In this case, the specification fails to disclose and there is no art-recognized correlation between the structure of the genus of antibodies and the required functions of recognizing/binding to β1AR and treating cardiovascular disease or Systemic Sclerosis. In other words, the specification does not teach the structure (i.e., heavy and light chain variable domains or CDRs) which results in an antibody with the claimed required characteristics. The specification also does not teach any monoclonal, human, or humanized antibodies (as recited by instant claims 4 and 13). The general description of purified IgG3(+) autoantibodies from patients in the instant specification at pages 16 and 20, is not adequate written description of an entire genus of antibodies that recognize/bind to β1AR and treat cardiovascular disease or Systemic Sclerosis. Applicant is reminded that generally, in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one or two species within the genus (Enzo Biochem, Inc. v. Gen-Probe Inc., 323 F.3d 956 (Fed. Cir. 2002); Noelle v. Lederman, 355 F.3d 1343 (Fed. Cir. 2004); Regents of the University of California v. Eli Lilly Co., 119 F.3d 1559 (Fed. Cir. 1997)). A patentee must disclose “a representative number of species within the scope of the genus of structural features common to the members of the genus so that one of skill in the art can visualize or recognize the member of the genus” (see Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017) at page 1358). An adequate written description must contain enough information about the actual makeup of the claimed products – “a precise definition, such as structure, formula, chemic name, physical properties of other properties, of species falling with the genus sufficient to distinguish the gene from other materials”, which may be present in “functional terminology when the art has established a correlation between structure and function” (Amgen page 1361).
The instant claims are attempting to claim administration of every IgG3 antibody that would achieve a desired result, i.e., recognizing/binding to β1AR and treating cardiovascular disease or Systemic Sclerosis, whereas the specification does not describe representative examples to support the full scope of the claims. Applicant is reminded that "when a patent claims a genus using functional language to define a desired result, the specification must demonstrate that the applicant has made a generic invention that achieves the same result and do so by showing that the applicant has invented species sufficient to support a claim to the functionally-defined genus" (Capon v. Eshhar, 418 F.3d 1349 (Fed. Cir. 2005)). However, in the instant case, the specification does not disclose the generation of a genus of IgG3 antibodies (or nucleic acids encoding such) that (i) recognize and bind to β1AR and (ii) treat cardiovascular disease or Systemic Sclerosis. Therefore, the specification does not provide adequate written description of an entire genus of IgG3 antibodies that achieve a desired result, i.e., recognizing/binding to β1AR and treating cardiovascular disease or Systemic Sclerosis.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states 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). See also, Amgen Inc. v. Sanofi, 124 USPQ2d 1354 (Fed. Cir. 2017), relying upon Ariad Pharms., Inc. v. Eli Lily & Co., 94 USPQ2d 1161 (Fed Cir. 2010). 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). A “mere wish or plan” to obtain the claimed invention is not sufficient (Centocor Orth Biotech, Inc. v. Abbott Labs, 636 F.3d 1341 (Fed. Cir. 2011); Regents of the Univ. of California, 119 F.3d at 1566). In the instant application, the skilled artisan cannot envision the detailed chemical structure of the antibodies and nucleic acids of the encompassed method claims, and therefore conception is not achieved until reduction to practice has occurred, 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 of isolating it. The specific antibody (and nucleic acid) is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016.
It is well-known in the art that antibodies have a large repertoire of distinct structures and that a large variety of antibodies can be made to bind to a single epitope. For example, Lloyd et al. teach that over hundreds of functional antibody fragments can be isolated from an antibody library that bind to the same antigen wherein these antibodies have distinct heavy and light chain sequences (Lloyd et al. Protein Engineering, Design & Selection 22:159-168, 2009; see, e.g., Discussion). Edwards et al. (J Mol Biol 334: 103-118, 2003; see abstract) also teach that over 1,000 different antibodies to a single Blys protein can be generated, all with different sequences, and representative of almost the entire extensive heavy and light chain germline repertoire, in addition to extensive diversity in the hCDR3 region sequences. Given that hundreds of unique antibody structures may bind a single antigen, one species or small group of related species cannot be representative of all the antibodies that bind to the same epitope. Given the unpredictability of the structures of the large number of antibodies that could bind to β1AR encompassed by the claims, the instant specification does not describe representative examples to support the full scope of the claims. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Applicant’s attention is directed to the recent decision in Amgen Inc. v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The court discussed whether an antibody is adequately described by describing a newly characterized antigen. Specifically, the court referred to the decision in Centocor Ortho Biotech, Inc. v. Abbott Labs., 636 F.3d 1341 (Fed. Cir. 2011). In that case, the patentee claimed a genus of antibodies containing a human variable region that has particularly desirable therapeutic properties: high affinity, neutralizing activity, and A2 specificity. Despite the fact that the specification disclosed human TNF-α protein, the court ruled that that the generic antibody claims at issue were invalid for lack of written description, despite the disclosure of the structures of more than one species of antibody encompassed in the genus. The fact pattern is similar in the instant case. Specifically, in the instant case, the structure of β1AR is known, while specific structures for IgG3 β1AR antibodies (and nucleic acids encoding such) that treat cardiovascular disease or Systemic Sclerosis are not. As in the court case, the instant claims recite a genus of antibodies that have a desirable therapeutic property, i.e., recognizing/binding to β1AR, and treating cardiovascular disease or Systemic Sclerosis. Following the finding in Centocor, the instant claims are found to lack adequate written description.
The court indicated that it has been hotly disputed whether or not knowledge of the chemical structure of an antigen gives the required kind of structure-identifying information about the corresponding antibodies. Citing Centocor again, the court provides an analogy for the antibody-antigen relationship as not quite a lock and key relationship but rather providing a lock and then searching for a key on a ring with a million keys on it. The court concludes that the “newly characterized antigen” test flouts basic legal principles of the written description requirement, reasoning that section 112 requires a written description of the invention, whereas the newly characterized antigen test allows patentees to claim antibodies by describing something that is not the invention, i.e., the antigen. The court urges that such constricts the “quid pro quo” of the patent system where one describes an invention in order to obtain a patent.
Accordingly, since the instant fact pattern fits the “newly characterized antigen” scenario, wherein the specification describes the structure of the target/antigen but not the structure of the genus of IgG3 antibodies, the claims do not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph.
Therefore, the claims do not meet the written description provision of 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). See also Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1355 (Fed. Cir. 2010).
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
3. Claims 1, 12, and 17-19 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Mohan et al. (bioRxiv doi.org//10.1101/2020.09.17.302059; 18 September 2020; cited on the IDS of 31 December 2025).
Mohan et al. teach a composition comprising IgG3(+) β1AR autoantibodies and a beta-blocker (metaprolol), meeting the limitations of instant claims 1, 17, and 18 (abstract; page 5, 1st and 2nd paragraphs (starting with the heading, “Role of β1AR autoantibodies on cAMP generation”); page 6, 1st paragraph; Figure 2D, 2E). Mohan et al. indicate that the IgG is purified from plasma samples, meeting the limitations of instant claim 19 (bottom of page 10 through the top of page 11). Mohan et al. disclose that IgG3(+) β1AR autoantibodies impair agonist-mediated G-protein coupling while preferentially mediating G-protein-independent ERK activation (abstract; pages 5-6). Mohan et al. teach that the uniqueness of the IgG3(+) β1AR autoantibodies lies in their ability to modulate β1A signaling to inhibit the classical agonist-mediated G-protein coupling, while effectively mediating G-protein-independent ERK activation in parallel (page 8). Mohan et al. continue to state that given the hyper-sympathetic state of patients with heart failure, the presence of the IgG3(+) β1AR autoantibodies would allow for preferential engagement of the G-protein-independent pathway, reflecting in the myocardial recovery of patients harboring the IgG3(+) β1AR autoantibodies, meeting the limitations of instant claim 1 (page 8). Mohan et al. teach that their study lays the foundation for using the subclass of IgG3(+) β1AR autoantibody as a therapeutic strategy because patients carrying IgG3(+) β1AR autoantibodies have significantly better outcomes that IgG3(-) patients, meeting the limitations of instant claim 1 (page 8).
.
Conclusion
No claims are allowable.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure:
Kawai et al. J Am Heart Assoc 15: e047402, 2026 (teach IgG3-β1 AR autoantibody positivity is associated with adverse outcomes in acute heart failure, especially among patients not treated with β-blockers)
Nagatomo et al. J Cardiac Failure 20(8): S23, #M056, 2014 (teach IgG3 Autoantibody Against b1-Adrenergic Receptors (but not total IgG) is Associated with More Favorable Outcome in Patients with Heart Failure
Nagatomo et al. J Cardiac Failure 21(8): S2-S28, #M040, 2015 (teach IgG3-β1 AR autoantibodies are associated with more favorable myocardial recovery in patients with recent onset cardiomyopathy)
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BEB
Art Unit 1647
09 July 2026
/BRIDGET E BUNNER/Primary Examiner, Art Unit 1647
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