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 .
This is the First Office Action on the Merits of US17/797,238 filed on 08/03/2020 which is a 371 of PCT/US2021/016434 filed on 02/03/2021 which claims US priority benefit of US Provisionals 63/074,742 filed on 09/04/2020 and 62/969,635 filed on 02/03/2020.
Election/Restrictions
Applicant’s election of Invention Group I (claims 489-502) in the reply filed on July 3, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 503-508 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 3, 2025.
Applicant’s election of species:
A) amino acid substitutions with respect to SEQ ID NO: 2 at positions K55 and F82 as the type of a single amino acid substitution or grouping of amino acid substitutions listed in claim 489;
B) SEQ ID NO: 13 as the type of SEQ ID NO 13-30, as listed in claim 494;
C) SEQ ID NO: 524 as the SEQ ID species from among claims 496-498; and
D) heteromultimer as the type of dimer among claims 499 and 500.
in the reply filed on July 3, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 496 and 499 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on July 3, 2025.
Claim status
Claims 1-488 are cancelled.
Claims 489-508 are pending.
Claims 503-508 are withdrawn to non-elected invention group.
Claim 496 and 499 are withdrawn to non-elected species.
Claims 489-495, 497-498, and 500-502 are under examination in this office action.
Information Disclosure Statement
The IDS statements filed on 01/16/2025, 06/15/2023, and September 15, 2025 have been considered by the examiner. The 09/15/2025 IDS has the No IDS size fee assertion box checked under 37 CFR 1.17(v).
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.
Claims 489-495, 497-498, and 500-502 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.
Regarding claim 489, the open ended limitation “one or more amino acid substitutions” showing forty-one substitutions does not correspond to the limitation in the claim that the variant ActRIIB amino acid sequence is at least 90% identical to a 114 amino acid sequence of SEQ ID NO: 2. Forty-one substitutions would result in less than 90% identical.
Claims 490-495, 497-498, and 500-502 are indefinite for the same reasoning as they depend from claim 489 and are not remedial.
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.
(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 489-492, 493-495, 497-498, and 500-502 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO2018/067874 to Kumar et al (published April 12, 2018; IDS ref).
WO2018067874 et al disclose a human variant ActRIIB protein.
Regarding claims 489, WO2018067874 discloses a protein comprising a variant ActRIIB amino acid sequence that is at least 90% identical to an amino acid sequence that begins at any one of amino acids 20-29 of instant SEQ ID NO: 2 and ends at any one of amino acids 109-134 of instant SEQ ID NO: 2, wherein the variant ActRIIB amino acid sequence comprises one or more amino acid substitutions with respect to SEQ ID NO: 2 at a position K55 or F82. Specifically, as evidenced by the STIC/SCV SEQ ID Result, WO2018067874 discloses a human ActRIIB protein variant F82Y which is 99.6 % identical to Instant SEQ ID NO: 1 (115aa) and is the following amino acid sequence: GRGEAETREC IYYNANWELE RTNQSGLERC EGEQDKRLHC YASWRNSSGT IELVKKGCWL DDFNCYDRQE CVATEENPQV YFCCCEGNFC NERFTHLPEA GGPEVTYEPP PTAPT. Note that SEQ ID NO: 1 is amino acid 20 to 134 of instant SEQ NO: 2.
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Regarding claim 490, WO2018067874 discloses that the variant ActRIIB amino acid sequence is at least 96% identical to amino acids 29-109 of SEQ ID NO: 2. (See STIC result just above showing 99% identity.)
Regarding claim 491, WO2018067874 discloses that the variant ActRIIB amino acid sequence is at least 96% identical to amino acids 20-134 of SEQ ID NO: 2. (See STIC result just above showing 99% identity.)
Regarding claim 492, WO2018067874 discloses that the variant ActRIIB amino acid sequence comprises an F82Y substitution.
Regarding claim 493, WO2018067874 discloses that the variant ActRIIB amino acid sequence comprises F82K substitution with respect to SEQ ID NO: 2. (See page 3, line 12).
Regarding claim 494, WO2018067874 discloses the protein of claim 489, wherein the protein is a fusion protein that further comprises an Fc polypeptide amino acid sequence that is at least 94% identical to SEQ ID NO: 13. (See page 10, line 31; page 11, lines 1-7).
Regarding claim 495, WO2018067874 discloses the protein of claim 494 further comprising a linker amino acid sequence between the variant ActRTTB amino acid sequence and the Fc polypeptide amino acid sequence, wherein the linker amino acid sequence is GGG or the amino acid sequence of any one of SEQ ID NOs: 262-267. (See page 10, lines 28-34.)
Regarding claims 497-498 WO2018067874 discloses the protein of claim 489, wherein the protein comprises an amino acid sequence that is at least 98% identical to the amino acid sequence of SEQ ID NO: 524. (See page 167, ref SEQ ID NO: 5).
Regarding claim 500 WO2018067874 discloses the protein of claim 489, wherein the protein is a heteromultimer. (See page 1, lines 30-31; Example 5; Page; 276)
Regarding claim 501, WO2018067874 discloses the protein of claim 500, wherein the protein further comprises an ALK4 polypeptide or an ALK7 polypeptide. (See page 20, line 5).
Regarding claim 502 WO2018067874 discloses the protein of claim 501, wherein the heteromultimer is a heterodimer. (See page 6, lines 28-32.)
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 489-491, 494-495, and 500 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 15 of U.S. Patent No. US 11,440,949.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate instant claims or the combination of patented claims renders obvious the instant claims.
Regarding instant claims 489-491, patented claim 15 recites a recombinant heteromultimer ActRIIB-FC fusion protein (95-98% identical to aa 20-134 of ref SEQ 1), wherein the ActRIIB-Fc fusion protein comprises patent SEQ ID NOs: 100 or 401. Each of ref SEQ ID NOs 100 and 401 contain a K55C substitution and a F82G substitution.
Regarding claim 494, patented claim 15 anticipates the protein of instant claim 489, wherein the protein is a fusion protein that further comprises an Fc polypeptide amino acid sequence that is at least 94% identical to instant SEQ ID NO: 13. Note instant SEQ ID NO:13 is a 225 amino acid sequence which is within the patented SEQ ID NOs: 100 and 401.
Regarding claim 495, patented claim 8 recites a linker amino acid sequence between the variant ActRIIB amino acid sequence and the Fc polypeptide amino acid sequence, wherein the linker amino acid sequence is the amino acid sequence of GGGG which is identical to instant SEQ ID NO: 262.
Regarding claim 500 patented claim 15 recites that the protein is a heteromultimer.
Thus, patented claim 15 anticipates instant claims 489-491, 494, 497-498, and 500. The combination of patented claims 8 and 15 renders obvious instant claim 495. It would have been obvious to combine the elements of patented claims 15 with the linker sequence of patented claim 8 for the rationale of making an effective therapeutic fusion protein comprising ActRIIB and ALK3-Fc. It would have been obvious to do such because patented claim 8 depends from claim 1 and is a preferred embodiment to such fusion protein.
Claim 489 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6 and 12 of U.S. Patent No. US 9,932,379.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate the instant claim.
Regarding instant claim 489, patented claims 6 and 12 recite a method comprising a variant polypeptide comprising an amino acid sequence of SEQ ID NO:26, or consisting of SEQ ID NO:28, respectively which meets the limitation of a protein comprising a variant ActRIIB amino acid sequence that is at least 90% identical to an amino acid sequence that begins at any one of amino acids 20-29 of SEQ ID NO: 2 and ends at any one of amino acids 109-134 of SEQ ID NO: 2, wherein the variant ActRIIB amino acid sequence comprises one or more amino acid substitutions with respect to SEQ ID NO: 2 at a position K55, and F82.
Claims 489-491, 494, and 500 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-29 of U.S. Patent No. US 9,399,669.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate instant claims or the combination of patented claims renders obvious the instant claims.
Regarding instant claims 489-490, patented claim 4 recites a variant polypeptide comprising an amino acid sequence of SEQ ID NO:2, that is at least 95% identical to an amino acid sequence that begins at any one of amino acids 20-29 of instant SEQ ID NO: 2 and ends at any one of amino acids 109-134 of instant SEQ ID NO: 2, wherein the variant ActRIIB amino acid sequence comprises one or more amino acid substitutions with respect to SEQ ID NO: 2 at a position K55, or F82.
Regarding instant claims 491, patented claim 9 recites a variant polypeptide comprising an amino acid sequence of SEQ ID NO:2, that is at least 98% identical to an amino acid sequence that begins at any one of amino acids 20-29 of instant SEQ ID NO: 2 and ends at any one of amino acids 109-134 of instant SEQ ID NO: 2, wherein the variant ActRIIB amino acid sequence comprises one or more amino acid substitutions with respect to SEQ ID NO: 2 at a position K55, or F82.
Regarding claim 494, patented claim 26 that the protein is a fusion protein that further comprises an Fc polypeptide amino acid sequence comprises instant SEQ ID NO: 13.
Regarding claim 500 patented claim 25 recites that the protein is a heteromultimer.
Claims 489-491 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30 of U.S. Patent No. 8,710,016.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate instant claims or the combination of patented claims renders obvious the instant claims.
Regarding instant claims 489-491, patented claims 1 and 13 recite a variant polypeptide comprising an amino acid sequence of reference SEQ ID NO: 23 which meets the limitation of a variant polypeptide comprising an amino acid sequence of instant SEQ ID NO:2, that is at least 98% identical to an amino acid sequence that begins at any one of amino acids 20-29 of instant SEQ ID NO: 2 and ends at any one of amino acids 109-134 of instant SEQ ID NO: 2, wherein the variant ActRIIB amino acid sequence comprises one or more amino acid substitutions with respect to SEQ ID NO: 2 at a position K55, or F82. Reference SEQ ID NO: 23 has a K55L and an F82G substitution.
Claims 489-491are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10, 13-18 and 24 of U.S. Patent No. 8,058,229.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate instant claims or the combination of patented claims renders obvious the instant claims.
Regarding instant claims 489-491, patented claims recite a variant polypeptide comprising the sequence of reference SEQ ID NO: 28 which meets the limitation of an amino acid sequence of instant SEQ ID NO:2, that is at least 98% identical to an amino acid sequence that begins at any one of amino acids 20-29 of instant SEQ ID NO: 2 and ends at any one of amino acids 109-134 of instant SEQ ID NO: 2, wherein the variant ActRIIB amino acid sequence comprises one or more amino acid substitutions with respect to SEQ ID NO: 2 at a position K55, or F82. Reference SEQ ID NO: 28 has a K55Asp and F82G substitution.
Claims 489-491 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 16 of U.S. Patent No. 8,138,142
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented claims anticipate instant claims or the combination of patented claims renders obvious the instant claims.
Regarding instant claims 489-491, patented claim 16 recites a variant polypeptide comprising an amino acid sequence of reference SEQ ID NO: 23 which meets the limitation of a variant polypeptide comprising an amino acid sequence of instant SEQ ID NO:2, that is at least 98% identical to an amino acid sequence that begins at any one of amino acids 20-29 of instant SEQ ID NO: 2 and ends at any one of amino acids 109-134 of instant SEQ ID NO: 2, wherein the variant ActRIIB amino acid sequence comprises one or more amino acid substitutions with respect to SEQ ID NO: 2 at a position K55, or F82. Reference SEQ 23 has a K55L and a F82G substitution.
Claim 489-495, and 500-501 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 45-47, 50-53 of copending Application No. 18/549,474 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims anticipate the present claims or the combination of copending claims render obvious the instant claims.
Regarding instant claims 489-493, copending claim 50 recites a method comprising a variant ActRIIB polypeptide comprising the amino acid sequence of SEQ ID NO: 2 with an amino acid substitutions including K55A, K55D, K55E, K55R, F82A, F82D, and F82K.
Regarding instant claim 494, copending claim 45 recites the Fc polypeptide.
Regarding instant claim 495, copending claim 47 recites identical linkers.
Regarding instant claim 500, copending claim 36 recites a heteromultimer.
Regarding instant claim 501, copending claim 36 recites an ALK4.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 489-495, and 500-501 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 11-13, 15-17, 19, 23-24, 26-31, 36-38, 44-45, 50-51 of copending Application No. 18/549,461 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims anticipate the present claims or the combination of copending claims render obvious the instant claims.
Regarding instant claims 489-493, copending claim 50 recites a method comprising a variant ActRIIB polypeptide comprising the amino acid sequence of SEQ ID NO: 2 with an amino acid substitutions including K55A, K55D, K55E, K55R, F82A, F82D, and F82K.
Regarding instant claim 494, copending claim 45 recites the Fc polypeptide.
Regarding instant claim 495, copending claim 45 recites linkers positioned between ActRIIB domain and the Fc domain.
Regarding instant claim 500, copending claim 36 recites a heteromultimer.
Regarding instant claim 501, copending claims 24, 26, 28-31, and 36 recites an ALK4.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 489, and 492-495 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 178-199 of copending Application No. 18/271,258 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending claims anticipate the present claims or the combination of copending claims render obvious the instant claims.
Regarding instant claims 489 and 492-493, copending claim 189 recites a method comprising a variant ActRIIB polypeptide comprising the amino acid sequence 90% identical to SEQ ID NO: 2 with an amino acid substitutions including K55A, K55D, K55E, K55R, F82A, F82D, and F82K. Copending claim 185 recites 95% identical to SEQ ID NO: 2.
Regarding instant claim 494, copending claims 178 and 182 recites the Fc polypeptide at least 95% identical to SEQ ID NO:13-17.
Regarding instant claim 495, copending claim 184 recites identical linkers positioned between ActRIIB domain and the Fc domain.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
An NSDP rejection over U.S. Patent No. US 10,259,861 is not required because the ‘861 claims require a K55 and a F82 to be present in ref SEQ ID NO: 5 whereas instant claims require an amino acid substitution at position K55 and/or F82.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE S HIBBERT whose telephone number is (571)270-3053. The examiner can normally be reached M-F 8:00-5:00.
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CATHERINE S. HIBBERT
Primary Examiner
Art Unit 1658
/CATHERINE S HIBBERT/Primary Examiner, Art Unit 1658