DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of Application, Amendments, And/Or Claims
Claims 1-23 are pending and under examination.
Information Disclosure Statement
The Information Disclosure Statements (2) filed on 7/19/2024 have been considered.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claim(s) 1, 3-9 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Donaldson et al. (Biochem. Biophys. Res. Commun. 184: 310-316, 1992).
A composition for therapeutic administration comprising a polypeptide and a pharmaceutically acceptable carrier, wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 2 (claim 1), wherein the polypeptide comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 2, wherein the polypeptide comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 2, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 2, wherein the polypeptide is glycosylated and has a mammalian glycosylation pattern, wherein the polypeptide has a glycosylation pattern obtainable from a Chinese hamster ovary (CHO) cell line, wherein the N-terminal amino acid is isoleucine, wherein the N-terminus of the polypeptide is ILGRSETQE (SEQ ID NO: 11)
Donaldson et al. teach a human activin receptor type II that binds to activin A having 100% sequence identity to the instantly claimed ActRIIA of SEQ ID NO: 2 (see sequence alignment us-18-443-985a-2.rpr, 6/8/2026). Regarding the limitations of claims 6-7, wherein the peptide has glycosylation pattern obtainable from CHO cell line, the instantly claimed peptide is 100% identical to the peptide taught by Donaldson et al., therefore, the instant peptide will have all the claimed inherent features, unless evidence to contrary. The instantly claimed peptide does have N-terminal peptide of Seq ID NO: 11. Therefore, the instantly claimed invention implicitly or explicitly are taught by the prior art of record.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-9, 11-12, 14-19 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Donaldson et al. (IDS, Biochem. Biophys. Res. Commun. 184: 310-316, 1992) in view of Haaning et al. (IDS, US Pub. No. 20040132971).
A composition for therapeutic administration comprising a polypeptide and a pharmaceutically acceptable carrier, wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 2 (claim 1), wherein the polypeptide is at least 98% pure as determined by size exclusion chromatography, wherein the polypeptide comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 2, wherein the polypeptide comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 2, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 2, wherein the polypeptide is glycosylated and has a mammalian glycosylation pattern, wherein the polypeptide has a glycosylation pattern obtainable from a Chinese hamster ovary (CHO) cell line, wherein the N-terminal amino acid is isoleucine, wherein the N-terminus of the polypeptide is ILGRSETQE (SEQ ID NO: 11) and wherein the composition is substantially pyrogen free.
Donaldson et al. teach a human activin receptor type II that binds to activin A having 100% sequence identity to the instantly claimed ActRIIA of SEQ ID NO: 2 (see sequence alignment us-18-443-985a-2.rpr, 6/8/2026). Donaldson et al do not teach a fusion of ActRIIA with an IgG-Fc.
Haaning et al. teach a pharmaceutical composition where the pharmaceutical composition comprises at least one pharmaceutical carrier or excipient [0063, 0332]. They teach that Remington’s Pharmaceutical Sciences 18th edition for guiding to make a pharmaceutical composition. They teach a fusion of a RANK protein with an immunoglobulin Fc [0063]. They teach that the fusion of an IgG-Fc can be prepared with a linker between a polypeptide to be fused with an IgG-Fc, wherein said linker can be a peptide linker or a PEG molecule [0063]. It is well known in the art that the fusion of an IgG-Fc to a polypeptide increases the half-life of said polypeptide. Regarding the limitations of claims 14-19, because the instantly claimed peptide has a 100% sequence identity to the instantly claimed polypeptide that binds to activin, it would inherently have the same feature to bind GDF11 and would have other characteristics of the peptide. “Patent and Trademark Office can require applicant to prove that prior art products do not necessarily or inherently possess characteristics of his claimed product where claimed and prior art products are identical or substantially identical, or are produced by identical or substantially identical processes; burden of proof is on applicant.” See in re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to prepare a fusion with an IgG-Fc as taught by Haaning et al in combination with the polypeptide encoding ActRIIA that binds to activin as taught by Donaldson et al. It would have been obvious to one ordinary skill in the art to also prepare a pharmaceutical composition of the fusion protein wherein the pharmaceutical composition comprises an excipient as taught by Haaning et al. Additionally, one would have been motivated to do so because Haaning et al teach making a fusion of a polypeptide with an IgG-Fc that in general increases the half-life of the conjugated polypeptide. Further, one would have a reasonable expectation of success in using an immunoglobulin Fc to conjugate with the polypeptide of Donaldson because it is routine to make a fusion of a polypeptide with an IgG-Fc using a linker or without linker. Therefore, the invention would have been obvious over the combined teachings of the prior art.
RESULT 1
JQ1486
activin receptor II precursor - human
N;Contains: serine/threonine-specific protein kinase (EC 2.7.1.-)
C;Species: Homo sapiens (man)
C;Date: 17-Jul-1992 #sequence_revision 19-Oct-1995 #text_change 05-Oct-2004
C;Accession: JQ1486; S18908; S22345
R;Donaldson, C.J.; Mathews, L.S.; Vale, W.W.
Biochem. Biophys. Res. Commun. 184, 310-316, 1992
A;Title: Molecular cloning and binding properties of the human type II activin receptor.
A;Reference number: JQ1486; MUID:92231944; PMID:1314589
A;Accession: JQ1486
A;Molecule type: mRNA
A;Residues: 1-513 <DON>
A;Cross-references: UNIPROT:P27037; UNIPARC:UPI0000126673; GB:M93415; NID:g178049; PIDN:AAA35504.1; PID:g178050
A;Experimental source: testis
R;Geiser, A.G.
submitted to the EMBL Data Library, December 1991
A;Reference number: S18908
A;Accession: S18908
A;Molecule type: mRNA
A;Residues: 1-513 <GEI>
A;Cross-references: UNIPARC:UPI0000126673; EMBL:X62381; NID:g28347; PIDN:CAA44245.1; PID:g28348
A;Experimental source: mammary gland epithelial cell line B5-589
R;Matzuk, M.M.; Bradley, A.
Biochim. Biophys. Acta 1130, 105-108, 1992
A;Title: Cloning of the human activin receptor cDNA reveals high evolutionary conservation.
A;Reference number: S22345; MUID:92182002; PMID:1311955
A;Accession: S22345
A;Molecule type: mRNA
A;Residues: 1-513 <MATZ>
A;Cross-references: UNIPARC:UPI0000126673; EMBL:X63128; NID:g3928172; PIDN:CAA44839.1; PID:g28350
C;Comment: This protein binds activin A.
C;Genetics:
A;Gene: GDB:ACVR2
A;Cross-references: GDB:132411
A;Map position: 11q13-11q13
C;Superfamily: Serine/threonine-specific protein kinase, activin receptor II type; protein kinase homology
C;Keywords: ATP; glycoprotein; phosphotransferase; receptor; serine/threonine-specific protein kinase; transmembrane protein
F;1-19/Domain: signal sequence #status predicted <SIG>
F;20-513/Product: activin receptor II #status predicted <MAT>
F;20-138/Domain: extracellular #status predicted <EXT>
F;139-160/Domain: transmembrane #status predicted <TM1>
F;161-513/Domain: intracellular #status predicted <INT>
F;190-486/Domain: protein kinase homology <KIN>
F;199-206/Region: protein kinase ATP-binding motif
F;43,66/Binding site: carbohydrate (Asn) (covalent) #status predicted
F;219/Active site: Lys #status predicted
Query Match 100.0%; Score 666; DB 1; Length 513;
Best Local Similarity 100.0%;
Matches 115; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ILGRSETQECLFFNANWEKDRTNQTGVEPCYGDKDKRRHCFATWKNISGSIEIVKQGCWL 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 ILGRSETQECLFFNANWEKDRTNQTGVEPCYGDKDKRRHCFATWKNISGSIEIVKQGCWL 80
Qy 61 DDINCYDRTDCVEKKDSPEVYFCCCEGNMCNEKFSYFPEMEVTQPTSNPVTPKPP 115
|||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 DDINCYDRTDCVEKKDSPEVYFCCCEGNMCNEKFSYFPEMEVTQPTSNPVTPKPP 135
Claim 10 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Donaldson et al. (IDS, Biochem. Biophys. Res. Commun. 184: 310-316, 1992) in view of Haaning et al. (IDS, US Pub. No. 20040132971) as applied to claims 24-30 above, and further in view of Sechler (IDS, US Pat. No. 5,523,232).
The instant invention is broadly drawn to the fusion protein of claim 1, further comprising the fusion polypeptide to be at least 95% pure and substantially free of pyrogen.
The teachings of Donaldson et al. and Haaning et al as set forth supra. Neither Donaldson et al nor Haaning et al teach that a pharmaceutical composition is free from pyrogen. Sechler et al. teach that pharmaceutical industry has long been able to prepare pyrogen -free preparations of hormones and other therapeutically useful proteins (col. 10, lines52+). They teach that REMINGTON’S Pharmaceutical sciences (18th ed. 1990) teaches that various techniques are routinely applied to express heterologous genes and make proteins and purify proteins. Sechler teaches that applying well-known techniques of protein purification, it has been possible to prepare substantially pure and pyrogen free preparations suitable of administration to human patients (col. 10-11).
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to purify and prepare pyrogen free pharmaceutical composition suitable of administering to a human patient as taught by Sechler using a fusion with an IgG-Fc as taught by Donaldson et al. in view of Haaning et al. Additionally, one would have been motivated to do so because Sechler teaches that a substantially pure and free of pyrogen preparation is suitable for human patients. Further, one would have a reasonable expectation of success in purifying a fusion protein to substantially pure to 95% or even more and to be free of pyrogen because Sechler teaches that purifying recombinant proteins to substantial pure and to be free from pyrogen is routine in the art. Therefore, the invention would have been obvious over the combined teachings of the prior art.
Claims 1, 3-5, 8-9, 11 and 13 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Donaldson et al. (IDS, Biochem. Biophys. Res. Commun. 184: 310-316, 1992) in view of Rosen et al. (WO 01/77137).
The instantly claimed invention is a composition for therapeutic administration comprising a polypeptide and a pharmaceutically acceptable carrier, wherein the polypeptide comprises an amino acid sequence that is at least 95% identical to SEQ ID NO: 2 (claim 1), wherein the polypeptide comprises an amino acid sequence that is at least 97% identical to SEQ ID NO: 2, wherein the polypeptide comprises an amino acid sequence that is at least 99% identical to SEQ ID NO: 2, wherein the polypeptide comprises the amino acid sequence of SEQ ID NO: 2, wherein the N-terminal amino acid is isoleucine, wherein the N-terminus of the polypeptide is ILGRSETQE (SEQ ID NO: 11) and wherein the fusion protein comprises serum albumin.
Donaldson et al. teach a human activin receptor type II that binds to activin A having 100% sequence identity to the instantly claimed ActRIIA of SEQ ID NO: 2 (see sequence alignment us-18-443-985a-2.rpr, 6/8/2026). Donaldson et al. do not teach a fusion protein comprising the amino acid sequence of SEQ ID NO: 2 and a domain that increases the half-life of the protein, wherein the domain is serum albumin.
Rosen et al. teach that hormones and peptides in general have short half-life and making a composition and for transporting for a longer period do require addition of serum albumin or like that (abstract, pg. 2, middle paragraph). They teach a making a fusion protein between human serum albumin and the peptide (summary of invention, pg. 2) to increase the half-life of the protein.
Therefore, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to use human serum albumin fusion as taught by Rosen et al to make a fusion protein with the peptide comprising amino acid sequence of SEQ ID NO: 2 as taught by Donaldson et al. Additionally, one would have been motivated to do so because Rosen teaches that the fusion protein with human serum albumin increases half-life of the protein. Further, one would have a reasonable expectation of success in using human SA to make a fusion with the instant protein comprising amino acid sequence of SEQ ID NO: 2 as taught by Rosen et al. Therefore, the instantly claimed invention would have been obvious over the combined teachings of the prior art.
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 1-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9-23, 33, 41-55, 57-58, 65,73-90, 97, 107-123 of U.S. Patent No. 8,629,109. Although the claims at issue are not identical, they are not patentably distinct from each other because a method of treating a bone disease, promoting bone growth comprising administering an effective amount of the composition comprising a polypeptide having at least 95%, at least 97% or 100% identity to the amino acid sequence of SEQ ID NO:2, wherein the compositions is administered no more frequently than once per month, wherein the composition is administered no more frequently than once every three months, wherein the composition is administered no more frequently than once every six months, wherein the polypeptide an amino acid sequence that is at least 95% identical to SEQ ID NO: 2, wherein the polypeptide is glycosylated and has a mammalian glycosylation pattern, wherein the polypeptide has a glycosylation pattern obtainable from a Chinese hamster ovary (CHO) cell line, wherein the N-terminal amino acid is isoleucine, wherein the N-terminus of the polypeptide is ILGRSETQE (SEQ ID NO: 11), wherein the composition is substantially pyrogen free, wherein the polypeptide further comprises a domain that enhances one or more of in vivo stability, in vivo half-life, uptake/administration, tissue localization or distribution, formation of protein complexes, or purification, wherein the domain is an immunoglobulin Fc domain are taught by claims 1, 9-23, 33, 41-55, 57-58, 65,73-90, 97, 107-123 of U.S. Patent No. 8,629,109.
Claims 1-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 and 18-23 of U.S. Patent No. 8,067360. Although the claims at issue are not identical, they are not patentably distinct from each other because a method of treating a bone disease, promoting bone growth comprising administering an effective amount of the composition comprising a polypeptide having at least 95%, at least 97% or 100% identity to the amino acid sequence of SEQ ID NO:2, wherein the compositions is administered no more frequently than once per month, wherein the composition is administered no more frequently than once every three months, wherein the composition is administered no more frequently than once every six months, wherein the polypeptide an amino acid sequence that is at least 95% identical to SEQ ID NO: 2, wherein the polypeptide is glycosylated and has a mammalian glycosylation pattern, wherein the polypeptide has a glycosylation pattern obtainable from a Chinese hamster ovary (CHO) cell line, wherein the N-terminal amino acid is isoleucine, wherein the N-terminus of the polypeptide is ILGRSETQE (SEQ ID NO: 11), wherein the composition is substantially pyrogen free, wherein the polypeptide further comprises a domain that enhances one or more of in vivo stability, in vivo half-life, uptake/administration, tissue localization or distribution, formation of protein complexes, or purification, wherein the domain is an immunoglobulin Fc domain are taught by claims 1-13 and 18-23 of U.S. Patent No. 8,067360.
Conclusion
No claim is allowed.
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/GYAN CHANDRA/Primary Examiner, Art Unit 1674
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