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 .
DETAILED ACTION
Election/Restrictions
Applicant’s election without traverse of species: diastolic dysfunction, SEQ ID NO: 367, polypeptide heteromultimer, SEQ ID NO: 261, SEQ ID NO: 380, ActRIIB polypeptide and an ALK4 polypeptide, SEQ ID NO: 86, SEQ ID NO: 130, SEQ ID NO: 53, SEQ ID NO: 12, and amino acid substitutions K55E and L79S for SEQ ID NO: 2 in the reply filed 05/11/2026 is acknowledged.
Claims 14, 17-21, 27-28, 30, 32, 34, 44-48 are withdrawn from consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions and species, there being no allowable generic or linking claims. Election was made in the reply filed 05/11/2026.
Claims 1-2, 4, 6, 13, 15, 23-24, 26, 36-38, 41, 50-53 are now under consideration in the instant Office Action.
Claim Objections
Claims 1-2, 4, 6, 13, 15, 23-24, 26, 36-38, 41, 50-53 are objected to because of the following informalities: the acronyms “ActRII” and “ALK4” should be accompanied by the full terminology the first time each appears in the claim; e.g., “activin receptor II (ActRII)” and “activin receptor kinase-4 (ALK4)”. Appropriate correction is required.
Claim 41 is objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only. See MPEP § 608.01(n). Accordingly, the claim 41 not been further treated on the merits.
Claim Rejections - 35 USC § 112
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 50 is 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.
Instant claim 50 recites SEQ ID NO: 2 with a list of potential amino acid substitutions. The recitation of “S26T” as a substitution with respect to SEQ ID NO: 2 is ambiguous because SEQ ID NO: 2 has T26. Applicant is encouraged to amend this claim to recite “T26S” to match the disclosure and the sequence listing.
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 1-2, 4, 6, 13, 15, 23-24, 26, 36-38, and 50-53 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.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112(a), it is necessary to understand what Applicants are claiming and what Applicants have possession of.
The invention to which the claims are directed is a method with the intended use of treating heart failure associated with diabetic cardiomyopathy, with this therapeutic effect asserted to be achieved by a single step of administering an “ActRII-ALK4 antagonist” to the patient. The specification teaches that “ActRII” refers to “a family of activin receptor type IIB” proteins (paragraph 0222, published application), and that “ALK4” refers to “a family of activin receptor-like kinase-4” proteins (paragraph 0291). The specification provides working examples in support of the claimed invention, which teach the following superior properties with respect to the heterodimer comprising an ActRIIB polypeptide-Fc fusion linked to an ALK4 polypeptide-Fc fusion as compared to an ActRIIB-Fc homodimer:
“…ActRIIB-Fc:ALK4-Fc heterodimer is a more selective antagonist of activin A, activin B, GDF8, and GDF11 compared to ActRIIB-Fc homodimer. Accordingly, an ActRIIB-Fc:ALK4-Fc heterodimer will be more useful than an ActRIIB-Fc homodimer in certain applications where such selective antagonism is advantageous. Examples include therapeutic applications where it is desirable to retain antagonism of one or more of activin A, activin B, activin AC, GDF8, and GDF11 but minimize antagonism of one or more of BMP9, BMP10, GDF3, and BMP6” (paragraph 0948).
The working examples further provide support for the claimed method with respect to treatment of heart failure, concluding in Example 16 that the “data demonstrate that ActRIIB-Fc:ALK4-Fc is effective to ameliorate deficits during left heart remodeling in a murine model of HFpEF (db/db model). In particular, E/e′ was significantly reduced in ActRIIB-Fc:ALK4-Fc treated mice compared to untreated groups, indicating that ActRIIB-Fc:ALK4-Fc improves LV relaxation. The data further suggest that, in addition to ActRIIB:ALK4 heteromultimers, other ActRII-ALK4 antagonists may be useful in treating heart failure”, (paragraph 981).
The specification teaches that the term “ActRII-ALK4 antagonist” refers to “a variety of agents that may be used to inhibit signaling by one or more ActRII-ALK4 ligands including, for example, antagonists that inhibit one or more ActRII-ALK4 ligands (e.g., activin A, activin B, GDF8, GDF11, BMP6, and/or BMP10); antagonists that inhibit one or more ActRII-ALK4 ligand associated receptors (e.g., ActRIIA, ActRIIB, ALK4, and ALK7); and antagonists that inhibit one or more downstream signaling components (e.g., Smad proteins such as Smads 2 and 3)”. Thus, the term “ActRIIB-ALK4 antagonist” is defined functionally without being limited to any particular molecular structure, and thus broadly encompasses any type of structure, such as a polypeptide, antibody, nucleic acid, small molecule, carbohydrate, lipid, inorganic molecule or other.
Instant claims 1-2, 4, 6, 13, 15, 23-24, and 36 do not recite any particular structure for the ActRII-ALK4 antagonist so long as the claimed function is achieved. The claims further expressly recite, in dependent claims 23 and 24, that the antagonist can be a “heteromultimer comprising an ActRII polypeptide and an ALK4 polypeptide”. These claims encompass ActRII and ALK4 polypeptides having any amino acid sequence or structure. Further dependent claims limit the amino acid sequences of the ActRII and ALK4 polypeptides to sequences defined with respect to reference sequences; e.g., claims 15, 26, 37-38, and 41. However, the claims only recite up to 90% of shared identity with the recited sequence and allows for a broad, unknown number of molecules that can arise from this degree of variability that Applicant does not have support for. Thus, the claims are directed to several genera, including a broad genus of ActRII-ALK4 antagonists having any type of molecular structure; a subgenus of such antagonists that are heteromultimers comprising ActRII and ALK4 polypeptides having any type of amino acid sequence; and further subgenera of such heteromultimers having ActRII and ALK4 polypeptides with 90% defined amino acid sequences.
Additionally, instant claims 50-53 recite a base sequence for the ActRIIB polypeptide, SEQ ID NO: 2, that can encompass one or more of the recited amino acid substitutions to the sequence, many of which are options for the same residue on the sequence. This broadens the scope of what is encompassed by the claims as a large number of sequence variations can arise from this language and Applicant has not provided disclosure for the possession of such molecules.
The instant specification provides extensive teachings regarding the amino acids that contribute to the ligand-binding domain of each protein (e.g., starting at paragraph 237 for ActRII, and starting at paragraph 307 for ALK4). Thus, with respect to the heteromultimers of the claims, the person of ordinary skill in the art would have recognized the teachings in the specification as being sufficient to provide written description for the genus of ActRII recited in dependent claim 15 and for the genus of ALK4 polypeptides recited in dependent claim 26.
While the teachings of the specification are sufficient to provide written description for the indicated scope of ActRII and ALK4 polypeptide variants, the claims are not limited to such, and encompasses variants in which an unlimited number of changes are made to the reference sequences. The prior art appreciates that "Mutations … are generally destabilizing, and can reduce protein … fitness" and "In general, more comprehensive understanding of how mutations affect protein fitness within living cells is needed, including their combined effects on function, thermodynamic and kinetic stability, and clearance through aggregation and degradation" (Tokuriki et al., in instant PTO-892). Thus, knowledge of the amino acid sequences of ActRII and ALK4 alone are not sufficient for the skilled artisan at the time of the effective filing date to predict which combinations of mutations (substitutions, additions and deletions) will result in a functional heteromultimer that is a functional antagonist corresponding in scope to the broad range of mutations encompassed by the claims.
With respect to the broader genus of ActRII-ALK4 antagonists that is defined by function alone (i.e., antagonism), a product defined by function is not in and of itself sufficient to describe the product because it is only an indication of what the product does, rather than what it is; i.e., the specific structure of the product. It is only a definition of a useful result rather than a definition of what achieves that result. Per MPEP 2124, "describing a composition by its function alone typically will not suffice to sufficiently describe the composition". Furthermore, in the instant case the specification does not establish a correlation between structure and function; e.g., the structure of one of ActRII-ALK4 antagonist does not provide predictability regarding other structures having the same functionality. Furthermore, as the genus encompasses antibodies, the decision of the Federal Circuit in Amgen v. Sanofi, 872 F.3d 1367 (Fed. Circ. 2017) is applicable; this held that a claim directed to an antibody requires written description of the antibody itself rather than being satisfied solely by a written description of the antigen to which it binds (the so-called "newly characterized antigen" test). Thus, a description of the target protein (e.g., ActRII or ALK4) is not in and of itself sufficient to provide a description of the genus of antibodies binding to said target.
Written description for a genus may also be satisfied through sufficient description of a relevant number of species. This is dependent on whether one of skill in the art would recognize necessary common attributes or features possessed by the members of the genus. Generally, in an unpredictable art, adequate description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. Also, “[w]hen 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 claimed 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)). “[A] sufficient description of a genus … requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus” (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69).
As noted above, the genus of ActRII-ALK4 antagonists encompasses inhibitors that have any structure; e.g., polypeptide, antibody, nucleic acid, small molecule, carbohydrate, lipid, inorganic molecule or other. Each of these types of molecules is a subgenus encompassing multiple structures. For example, ActRII-ALK4 antagonists that are antibodies include the entire range of monoclonal antibodies that bind to and inhibit ActRII or ALK4, as well as antibodies that indirectly inhibit the function of either protein, such as binding to a downstream signaling molecule. However, the specification does not provide examples of anti-ActRII or anti-ALK4 antibodies corresponding in scope to encompassed genus, and likewise does not provide examples of each of the other structural categories of antagonists (e.g., small molecules), which would be necessary to describe the entirety of the genus of antagonists. The working examples are limited to use of the aforementioned ActRII-ALK4 heteromultimer. Per MPEP 2163, "A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."). As such, the description of structures of ActRII-ALK4 antagonists does not correspond that which is claimed, and therefore the specification fails to provide a written description of the genus of ActRIIB-ALK4 antagonists.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111 (Fed. Cir. 1991), clearly states “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” (pg 1117). The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed” (pg 1116).
Therefore, only a method of treating heart failure (HF) associated with diabetic cardiomyopathy in a patient in need thereof, comprising administering to the patient an effective amount of an ActRII-ALK4 antagonist, wherein the antagonist is a heteromultimer comprising an ActRII polypeptide that comprises an amino acid sequence that is at least 90% identical to amino acids 25-131 of SEQ ID NO: 2, and comprising an ALK4 polypeptide that comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 387, but not the full breadth of the claim meets the written description provision of 35 U.S.C. §112, first paragraph. Applicants are reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (pg 1115).
Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-2, 4, 6, 13, 23-24, 26, 36-38, and 50-53 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Kumar et al. 2018, (U.S. 2018/0163187 A1, in IDS filed 02/02/2024).
Kumar teaches an “ALK4:ActIIRB heterodimer” that acts as antagonist, see paragraph 5. Kumar further teaches that “an ALK4:ActRIIB heteromultimer may be used to treat or prevent a disorder or condition selected from a group including … congestive heart failure”, see paragraph 228. The larger ActRII heterodimer comprises a human ActRIIA extracellular domain, see paragraph 0110. Additional teachings with respect to the use of the heteromultimer in treatment of congestive heart failure are provided at paragraphs 235, 252, and 268. Kumar further teaches use of the ALK4:ActRIIB heteromultimer for treatment of chronic kidney disease, and complication of kidney disease, which include congestive heart failure, see paragraph 252. This meets the limitations of instant claim 1 wherein a method of treating heart failure (HF) associated with diabetic cardiomyopathy in a patient in need thereof comprising administering an effective amount of an ActRII-ALK4 antagonist is taught, instant claim 13 wherein the ActRII heterodimer contains a ActRIIA polypeptide, instant claims 23 and 24 wherein the ActRII-ALK4 antagonist is a polypeptide heteromultimer, and instant claim 36 wherein the ActRII-ALK4 antagonist is a heteromultimer that comprises an ActRIIB polypeptide.
Kumar teaches that the ActRIIB polypeptide may have the sequence of SEQ ID NO: 1, see paragraph 118, which is 100% identical to instant SEQ ID NO: 2. As such, the teachings of Kumar also anticipate instant claims 37 and 38 wherein the sequence is at least 90% identical to SEQ ID NO: 2. Kumar et al. also teaches that within the ActRII extracellular domain, “the composite ActRII structures indicated that the ActRIIB-ligand binding pocket is defined, in part, by residues Y31, N33, N35, L38 through T41, E47, E50, Q53 through K55, L57, H58, Y60, S62, K74, W78 through N83, Y85, R87, A92, and E94 through F101. At these positions, it is expected that conservative mutations will be tolerated”, see paragraph 0110. Additionally, Kumar considers that “in certain preferred embodiments, heteromultimers of the disclosure comprise do not comprise an ActRIIB polypeptide wherein the position corresponding to L79 of SEQ ID NO: 1 is an acidic amino acid (i.e., is not a naturally occurring D or E amino acid residue or artificial acidic amino acid)”, see paragraph 0120. This meets the limitations of instant claims 50-53 wherein SEQ ID NO: 2 can be substituted at K55 and/or L79.
Kumar teaches that the ALK4 polypeptide may have the sequence of SEQ ID NO: 10, see paragraph 8, which is 100% identical to instant SEQ ID NO: 84. As such, the teachings of Kumar also anticipate instant claim 26 wherein the sequence is a match.
Each of claims 2, 4, and 6 limit the method of claim 1 by means of a “wherein” clause indicating a result of the claimed method. In each claim, the wherein clause has been fully considered in context of the entire claim, but does not render the claimed method patentably distinct from a method taught by the prior art because it simply expresses the intended result of a process step positively recited. See MPEP 2111.04, which states that a "whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited" (Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), quoting Minton v. Nat ’l Ass ’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)). Specifically, in claims 2, 4, 6, the claims simply express an intended result (decrease in LV hypertrophy, improved diastolic dysfunction) of a process step positively recited (administering an ActRIIB-ALK4 antagonist). As such, the teachings of Kumar that anticipate parent claim 1 and also meets the limitations of dependent claims 2, 4, and 6.
Therefore, claims 1-2, 4, 6, 13, 23-24, 26, 36-38, and 50-53 are anticipated by Kumar et al.
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.
Claims 1-2, 4, 6, 13, 15, 23-24, 26, 36-38, and 50-53 are rejected under 35 U.S.C. 103 as being unpatentable over Kumar et al., in view of Knopf et al. 2007 (in instant PTO-892).
The relevance of Kumar et al. is discussed above.
However, Kumar et al. does not teach the sequence for ActRIIA polypeptide. Knopf et al. remedies this deficiency.
Knopf et al. teaches an activin-binding ActRIIA polypeptide comprising SEQ ID NO: 2, which is a 100% sequence homology match to instant SEQ ID NO: 367.
It would be obvious at the time of the instant invention to use the method taught by Kumar et al., which is a method of treatment of heart failure in a patients associated with diabetic cardiomyopathy comprising administering an ActRIIB-ALK4 antagonist that is a ActRIIB-ALK4 heteromultimer with the teachings of Knopf et al., which discloses the identity of the polypeptide sequence. One would be motivated to combine the methods with the polypeptide with the expectation of providing a targeted approach to treating cardiomyopathy using the sequence of the prior art. In the absence of any evidence to the contrary, the person of ordinary skill in the art would reasonably expect a peptide taught by Knopf et al., which it is expected to have a high degree of selectivity for activin inhibition over GDF11/GDF8 inhibition, could be used in the treatment taught for diabetic cardiomyopathy in general, such as that of Kumar, and be applicable to a number of diseases impacting the same molecular pathways and etiologies. This rationale supports a prima facie conclusion of obviousness in accord with KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (2007).
Therefore, claims 1-2, 4, 6, 13, 15, 23-24, 26, 36-38, and 50-53 are rejected as being obvious over Kumar et al. and Knopf et al.
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.
Claims 1, 2, 4, 6, 23-24, 36-38, and 50-53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 300-319 of copending Application No. 18/010,888, hereinafter ‘888 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the `888 application are directed to methods of treating heart failure (HF) in a patient in need thereof, comprising administering to the patient an effective amount of an ActRIIB-ALK4 antagonist, wherein the ActRIIB-ALK4 antagonist is a heteromultimer comprising an ActRIIB polypeptide and an ALK4 polypeptide, wherein the ActRIIB polypeptide comprises an amino acid sequence that is at least 90% identical to an amino acid sequence of SEQ ID NO: 2 or wherein the ActRIIB polypeptide comprises an amino acid sequence that is at least 90% identical to amino acids 25-131 of SEQ ID NO: 2, wherein the ALK4 polypeptide comprises an amino acid sequence that is at least 90% identical to an amino acid sequence of SEQ ID NO: 84 or wherein the ALK4 polypeptide comprises an amino acid sequence that is at least 90% identical to SEQ ID NO: 86, wherein the patient has: I.normal left ventricular ejection fraction (LVEF) and an LVEF of >50%;ii. reduced LVEF and an LVEF of <40%;iii. mid-range LVEF and an LVEF of between about 40% and about 49%;iv diastolic dysfunction of the left ventricle (LV); or v. systolic dysfunction of the left ventricle (LV), wherein the patient has elevated levels of natriuretic peptides, wherein the heart failure is heart failure with mid-range ejection fraction (HFmrEF) or reduced ejection fraction (HFrEF), wherein the method improves diastolic dysfunction.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 4, 6, 13, 15, 23-24, 26, 36-38, and 50-53 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 23-24, 36-38, 44-45, 48-51 of copending Application No. 18/549,461, hereinafter ‘461 (reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the `461 application are directed to methods of treating heart failure associated with aging, comprising administering to a patient in need thereof an effective amount of an ActRII-ALK4 antagonist, wherein the patient is obese, or has at least one of diabetes, left ventricular (LV) hypertrophy, diastolic dysfunction, and decreased ventricular relaxation and increased filling pressures, wherein the heart failure is heart failure associated with preserved ejection fraction (HFpEF), wherein the method decreases LV hypertrophy; improves diastolic dysfunction; increases ventricular relaxation and decreases filling pressures; decreases ratio of early diastolic trans mitral flow to early diastolic mitral annular tissue velocity (E/e' ratio); or decreases brain natriuretic peptide (BNP) levels in the patient, wherein the ActRII-ALK4 antagonist is a polypeptide heteromultimer, wherein the heteromultimer comprises an ActRIIB polypeptide and an ALK4 polypeptide or an ActRIIB polypeptide and an ALK7 polypeptide, wherein the ActRII-ALK4 antagonist is a heteromultimer that comprises an ActRIIB polypeptide, wherein the ActRIIB polypeptide comprises an amino acid sequence that is at least 90% identical to an amino acid sequence that begins at any one of amino acid residues 20, 21, 22, 23, 24, 25, 26, 27, 28, or 29 of SEQ ID NO: 2 and ends at any one of amino acid residues 109, 110, 111, 112, 113, 114, 115, 116, 117, 118, 119, 120, 121, 122, 123, 124, 125, 126, 127, 128, 129, 130, 131, 132, 133, or 134 of SEQ ID NO: 2, wherein the ActRIIB polypeptide comprises an amino acid sequence that is at least 90% identical to amino acids 29-109, 25-131, or 20-134 of SEQ ID NO: 2, wherein the ActRIIB polypeptide comprises an amino acid sequence that is at least 90% identical to the amino acid sequence of SEQ ID NO: 53, SEQ ID NO: 388, or SEQ ID NO: 389, wherein the ActRIIB polypeptide comprises an amino acid sequence as set forth in SEQ ID NO:2 with one or more amino acid substitutions with respect to the amino acid sequence of SEQ ID NO: 2 selected from the group consisting of: A24N, S26T, N35E, E37A, E37D, L38N, R40A, R40K, S44T, L46V, L46I, L46F, L46A, ESOK, ESOP, ESOL, E52A, E52D, E52G, E52H, E52K, E52N, E52P, E52R, E52S, E52T, E52Y, Q53R, Q53K, Q53N, Q53H, D54A, K55A, K55D, K55E, K55R, R56A, L57E, L57I, L57R, L57T, L57V, Y60D, Y60F, Y60K, Y60P, R64A, R64H, R64K, R64N, N65A, S67N, S67T, G68R, K74A, K74E, K74F, K74I, K74R, K74Y, W78A, W78Y, L79A, L79D, L79E, L79F, L79H, L79K, L79P, L79R, L79S, L79T, L79W, D80A, D80F, D80G, D80I, D80K,D80M, D80N, D80R, F82A, F82D, F82E, F82I, F82K, F82L, F82S, F82T, F82W, F82Y, N83A, N83R, T93D, T93E, T93G, T93H, T93K, T93P, T93R, T93S, T93Y, E94K, Q98D, Q98E, Q98K, Q98R, V99E, V99G, V99K, E1O5N, F108I, F108L, F108V, F108Y, E111D, E111H, E111K, 111N, E111Q, E111R, R112H, R112K, R112N, R112S, R112T, A119P, A119V, G120N, E123N, P129N, P129S, P130A, P130R, and A132N, wherein the ActRIIB polypeptide comprises an amino acid substitution that is K55E with respect to the amino acid sequence of SEQ ID NO: 2, wherein the ActRIIB polypeptide comprises an amino acid substitution that is L79S with respect to the amino acid sequence of SEQ ID NO: 2, wherein the ActRIIB polypeptide comprises an amino acid sequence as set forth in SEQ ID NO:2 with one or more amino acid substitution substitutions with respect to the amino acid sequence of SEQ ID NO: 2 selected from the group consisting of: L38N, E5OL, E52D, E52N, E52Y, L57E, L57I, L57R, L57T, L57V, Y60D, G68R, K74E, W78Y, L79E, L79F, L79H, L79R, L79S, L79T, L79W, F82D, F82E, F82I, F82K, F82L, F82S, F82T, F82Y, N83R, E94K, and V99G.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SELAM BERHANE whose telephone number is (571)272-6138. The examiner can normally be reached Monday - Friday, 9-5.
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, Jeffrey Stucker can be reached at 571-272-0911. 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.
/SELAM BERHANE/Examiner, Art Unit 1675
/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
Prosecution Insights