DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Election/Restrictions
Applicant’s response to the Election/Restriction requirement dated 3 February 2026 is acknowledged. Applicant elects a species of substitution of S428F and has amended the claims to recite only S428F and SEQ ID NO: 1. Although the election does not specify whether it is made with or without traverse, because Applicant did not distinctly and specifically point out supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP §818.01(a)).
Claim Status
Claims 12, 14, 15, 18-20, 72, and 73 are pending and under examination in the instant office action.
Information Disclosure Statement
Applicants are kindly reminded of their duty to disclose pursuant to 37 C.F.R. 1.56 which encompasses the citation of references material to patentability of which Applicants are aware, such as references that may have been cited in the International Search Report of the parent applicant or in the specification.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings. Please see the enumerated sequences in Fig. 2 and Fig. 3.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claims 18 and 19 are objected to because of the following informalities: claims 18 and 19 recite an "Fc constant region having CH3 domain" and "Fc constant region having CH2 and CH3 domain", respectively. The phrases are missing articles; the Examiner believes the claims should read "Fc constant region having a CH3 domain" and "Fc constant region having a CH2 and a CH3 domain", respectively. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 15 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.
Claim 15 is indefinite for the recitation of “wherein the polypeptide is a polypeptide of a feline or felinized IgG”. The metes and bounds of the claim are unclear because it is not certain what it would mean for a polypeptide to be “of” a feline IgG. For example, it is unclear if a polypeptide is “of” a feline IgG if it is a fusion protein between a non-feline protein and the feline IgG constant CH2 and CH3 domains or whether the claim is restricted solely to polypeptides consisting of sequences of feline immunoglobulin G proteins only.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 15 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 15 does not further limit claim 12 because the claim recites “wherein the polypeptide is a polypeptide of a feline or a felinized IgG”. This is broader than claim 12 because claim 12 requires that the polypeptide comprise a feline IgG constant domain; if the IgG domain is felinized, by definition it comprises non-feline sequence and therefore is not a feline IgG constant domain.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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 12, 18-20, and 72-73 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 20080287657 to Hinton et. al published 20 November 2008 as evidenced by “IMGT Scientific Chart: Correspondence between C numberings: Human IGHG”, imgt.org, accessed 23 March 2026, Web (hereinafter ‘IMGT’).
Claim interpretation: The instant claims are directed towards a polypeptide comprising: a feline IgG constant domain comprising at least one amino acid substitution relative to a wild-type feline IgG constant domain, wherein said substitution is at amino acid residue 428 numbered according the EU index as in Kabat, and wherein said substitution is S428F (emphasis is the Examiner’s). Regarding the definition of a feline IgG constant domain, the instant specification states, “The Fc region of an immunoglobulin generally comprises two constant domains, CH2 and CH3. In some embodiments, variants having one or more of the constant domains are contemplated. In other embodiments, variants without such constant domains (or with only portions of such constant domains) are contemplated” [00052], emphasis is the Examiner’s. Thus, the broadest reasonable interpretation of the instant claims is a polypeptide comprising a portion of the feline IgG Fc (reads “constant domain”) comprising at least on substitution relative to a wild-type feline IgG constant domain, wherein said substitution is at amino acid residue 428 numbered according to EU numbering and wherein the substitution is S428F. The examiner notes that, additionally, there is no ceiling on the “or more” substitutions, and therefore the IgG constant domain encompasses IgG domains from virtually any species which comprise additional substitutions relative the feline IgG constant domain.
Hinton et. al. teaches Fc fusion protein in which at least one amino acid from the heavy chain region selected from the group consisting of amino acid residues 250, 314, and 428 is substituted compared to an unmodified fusion protein, thereby altering the affinity for FcRn (abstract). Hinton et. al. teaches SEQ ID NO: 43 ([0060], Table 1), which comprises a portion of an IgG constant domain from residues 308-330 which is 100% identical to the portion of the instant feline IgG constant domain of instant SEQ ID NO: 1 residues 313-335 except for an F at position 428 by EU numbering.
Regarding claims 18 and 19, as evidenced by IMGT, SEQ ID NO: 43 comprises a CH2 and CH3 domain.
Regarding claim 20, as described for claim 12 above, the portion of SEQ ID NO: 43 residues 308-330 is 100% identical to the portion of wild-type feline IgG of instant SEQ ID NO: 1 residues 313-335 except for the F at position 428 by EU numbering:
Regarding claim 72, Hinton et. al. teaches formulations comprising the modified Fc-fusion protein and a pharmaceutically acceptable carrier [124].
Regarding claim 73, Hinton et. al. teaches kits comprising the modified Fc-fusion proteins in a lyophilized form in a container with a set of instructions for use [130].
Claim Rejections - 35 USC § 103
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 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 12 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. 20220009994 to Brondyk et. al. effectively filed 10 July 2020; WO2020082048 A1 to Zhan et. al. published 23 April 2020; and U.S. 20080287657 to Hinton et. al published 20 November 2008 as evidenced by “IMGT Scientific Chart: Correspondence between C numberings: Human IGHG”, imgt.org, accessed 23 March 2026, Web (hereinafter ‘IMGT’).
Claim interpretation: The instant claims are directed towards a polypeptide comprising: a feline IgG constant domain comprising at least one amino acid substitution relative to a wild-type feline IgG constant domain, wherein said substitution is at amino acid residue 428 numbered according the EU index as in Kabat, and wherein said substitution is S428F. Regarding the definition of a feline IgG constant domain, the instant specification states, “The Fc region of an immunoglobulin generally comprises two constant domains, CH2 and CH3. In some embodiments, variants having one or more of the constant domains are contemplated. In other embodiments, variants without such constant domains (or with only portions of such constant domains) are contemplated”. Thus, the broadest reasonable interpretation of the instant claims is a polypeptide comprising a portion of the feline IgG constant domain comprising at least on substitution relative to a wild-type feline IgG constant domain, wherein said substitution is at amino acid residue 428 numbered according to EU numbering and wherein the substitution is S428F. The examiner notes that, additionally, there is no ceiling on the “at least one” substitutions, and therefore the IgG constant domain encompasses IgG domains from virtually any species which comprise additional substitutions relative the feline IgG constant domain.
The examiner further notes that claim 14 recites the polypeptide of claim 12 “wherein the polypeptide has a higher affinity for FcRn than the polypeptide of the IgG having the wild-type feline IgG constant domain”. The claim does not specify that the IgG has a higher affinity for feline FcRn; therefore, the polypeptide may have a higher affinity for FcRn from any species.
Brondyk et. al. teaches polypeptides such as polypeptide-Fc region fusions or antibodies that have increased half-life in felines compared to their wild-type counterparts, wherein the polypeptides have increased binding to feline FcRn [0001-0004].
Brondyk et. al. teaches a feline IgG comprising two or more amino acid substitutions, wherein the two or more amino acid substitutions are selected from the “(i) an amino acid substitution at a position that corresponds to amino acid position 252 of a wild type feline IgG, wherein the amino acid substitution is selected from the group consisting of S252W, S252Y, S252F and S252R; (ii) an amino acid substitution at a position that corresponds to amino acid position 254 of a wild type feline IgG, wherein the amino acid substitution is selected from the group consisting of S254R and S254K; (iii) an amino acid substitution at a position that corresponds to amino acid position 309 of a wild type feline IgG, wherein the amino acid substitution is selected from the group consisting of L309V, L309Y and L309E; (iv) an amino acid substitution at a position that corresponds to amino acid position 311 of a wild type feline IgG, wherein the amino acid substitution is selected from the group consisting of Q311R, Q311V, Q311L and Q311K; (v) an amino acid substitution at a position that corresponds to amino acid position 428 of a wild type feline IgG, wherein the amino acid substitution is selected from the group consisting of S428L, S428M, S428Y, S428H and S428R; [0030] (vi) an amino acid substitution at one or more positions that correspond to amino acid positions selected from the group consisting of 262, 286, 289, 290, 293, 301, 312, 326, 334, 347, 355, 377, 380, 383, 389c, 392, 426 and 437 of a wild type feline IgG; and (vii) an amino acid substitution at a position that corresponds to amino acid position 434 of a wild type feline IgG, wherein the amino acid substitution is selected from the group consisting of S434F, S434W, S434H, S434R, and S434Y; wherein the amino acid positions are based on EU numbering, wherein the two or more amino acid substitutions are at different positions, and wherein the polypeptide has increased binding affinity to feline FcRn when compared to (a) an Fc domain of the wild type feline IgG, and (b) a polypeptide comprising only one of the two or more amino acid substitutions” ([0024]).
Brondyk et. al. teaches that variants in IgG1a Fc feline backbones at the S428 position S428L, S428M, S428Y increase feline FcRn affinity for the Fc domain (KD in single or duplicate were: 4.85E-7 and 7.63E-7; 6.03E-7; and 5.28E-7 and 5.65E-7), respectively ((Table 3); see [0157]). Brondyk et. al. teaches that all substitutions at position 428 were tested except for S428F and S428W [0236].
Zhan et. al. teaches Fc variants with altered binding to neonatal Fc receptor (FcRn) for veterinary use including felines (Abstract). Zhan teaches a feline Fc receptor sequence with a mutation of a leucine or a tryptophan at a position corresponding to 202 in SEQ ID NO: 12 (p. 13 ¶1; Examples 13-15 [00199-00207]). Zhan et. al. teaches that conservative substitutions are contemplated and the Phe is a conservative substitution for leucine, tryptophan, and tyrosine (Table 3, p. 61-62).
Hinton et. al. teaches Fc fusion protein in which at least one amino acid from the heavy chain region selected from the group consisting of amino acid residues 250, 314, and 428 is substituted compared to an unmodified fusion protein, thereby altering the affinity for FcRn (abstract). Hinton et. al. teaches SEQ ID NO: 43 ([0060], Table 1), which comprises a portion of an IgG constant domain from residues 308-330 which is 100% identical to the portion of the instant feline IgG constant domain of instant SEQ ID NO: 1 residues 313-335 except for an F at position 428 by EU numbering.
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to combine the teachings of Brondyk et. al., Zhan et. al., and Hinton et. al. in order to benefit from making a feline Fc domain in order to extend the half-life of the feline Fc domain by increasing the binding to FcRn by combining mutations at in the feline Fc domain as taught by Brondyk et. al. and Zhan et. al. (e.g. Q311R as taught by Brondyk) with the remaining untested residues F at position 248 as taught by Brondyk and by Hinton et. al. This would have a reasonable expectation of success because 1) Brondyk et. al. and Zhan et. al. both teach combinations of mutations at positions in a feline Fc domain that increase feline Fc binding to feline FcRn; 2) Brondyk et. al. and Zhan et. al. both teach mutations at position 248 that increase or do not decrease the binding of feline Fc to feline FcRn when it is the only mutation; 3) Brondyk et. al. and Zhan et. al. teach S428W, S428Y, and S428L which would be a conservative mutations to S428F; 4) the human and feline FcRn sequences are 100% identical in this portion of the Fc region and Hinton et. al. teaches that the M428F mutation increases binding to human FcRn. Therefore, a person of ordinary skill in the art would expect to be able to design a Fc region that has increased binding to FcRn for a longer half-life in felines as taught by Brondyk et. al. and Zhan et. al. by using the mutations of Brondyk et. al. and Zhan et. al. combined with S428F, which an artisan would expect to either not disrupt Fc/FcRn binding or to improve Fc/FcRn binding based on the teachings of Brondyk et. al., Zhan et. al., and Hinton 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 12, 14, 15, 18-20, 72, and 73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 156-169 of copending Application No. 17918860 in view of U.S. 20220009994 to Brondyk et. al. effectively filed 10 July 2020; WO2020082048 A1 to Zhan et. al. published 23 April 2020; and U.S. 20080287657 to Hinton et. al published 20 November 2008.
This is a provisional nonstatutory double patenting rejection.
The claims of ‘860 recite a method for increasing the serum half-life of a feline IgG in a cat and a composition of a feline IgG comprising a mutant feline IgG constant domain and a feline IgG variable domain, wherein the mutant feline IgG constant domain comprises the amino acid substitution of serine at position 428 with leucine and wherein 434, 436, 438, 440, 259, and 308 have wildtype residues (claim 156, 162); wherein the IgG comprises an Fc constant having CH2 domain (claim 157, 159, 163, 165); wherein the IgG comprises an Fc constant region having CH3 domain (claim 158, 159, 164, 165); wherein the wild-type feline IgG constant domain comprises the amino acid sequence set forth in SEQ ID NO: 3 (166); and pharmaceutical compositions and carriers (claim 168) as well as fusion molecules comprising the IgG (claim 169).
Thus, the main difference between the claims of ‘860 and the instant application is that the claims of ‘860 recite a substitution to leucine at position 428 rather than a substitution to phenylalanine (F).
This deficiency is resolved by Brondyk et. al., Zhan et. al., and Hinton et. al.
The teachings of Brondyk et. al., Zhan et. al., and Hinton et. al. are in the 103 rejection above and are incorporated by reference herein. In particular, Brondyk et. al. and Zhan et. al. teach feline IgG domains comprising mutations that increase affinity to FcRn wherein positions 434, 436, 438, 440, 259, and 308 have wildtype residues (e.g. a mutation at residue 311).
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to substitute 428F mutation that had not yet been tried by Brondyk et. al. in the feline IgG domain of ‘860 with a mutation such as the 311R mutation in order to increase the affinity of the IgG for FcRn as taught by Brondyk et. al. and Zhan et. al. This would have a reasonable expectation of success 1) ‘860, Brondyk et. al., and Zhan et. al. both teach combinations of mutations at positions in a feline Fc domain that increase feline Fc binding to feline FcRn; 2) ‘860, Brondyk et. al., and Zhan et. al. all teach mutations at position 248 that increase or do not decrease the binding of feline Fc to feline FcRn when it is the only mutation; 3) Brondyk et. al. and Zhan et. al. teach S428W, S428Y, and S428L which would be a conservative mutations to S428F; 4) the human and feline FcRn sequences are 100% identical in this portion of the Fc region and Hinton et. al. teaches that the M428F mutation increases binding to human FcRn. Therefore, a person of ordinary skill in the art would expect to be able to design a Fc region that has increased binding to FcRn for a longer half-life in felines as taught by ‘860, Brondyk et. al., and Zhan et. al. by using the mutations of Brondyk et. al. and Zhan et. al. combined with S428F, which an artisan would expect to either not disrupt Fc/FcRn binding or to improve Fc/FcRn binding based on the teachings of Brondyk et. al., Zhan et. al., and Hinton et. al.
Claims 12, 14, 15, 18-20, 72, and 73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 155-156, 158, 160, 162-165, 166, 168-169 of copending Application No. 18246725 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of '725 make obvious the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The claims of ‘725 recite a method for increasing the serum half-life of a feline IgG in a cat and a composition of a feline IgG comprising a mutant feline IgG constant domain and a feline IgG variable domain wherein the feline IgG constant domain comprises a substitution at position 434 with histidine (claims 155 and 165) and wherein the IgG constant domain comprises an additional substitution at position 428 (claims 156 and 166). In order to determine the scope of the claimed genus of substitutions at 428, the specification was consulted (MPEP 804.II.B.1). The specification of ‘725 teaches the substitution S428F in a feline IgG domain that increases FcRn binding to the IgG domain (Table 5A, [000212]).
Regarding claim 15, the antibody comprises non-feline CDRs so the polypeptide is a felinized antibody.
Regarding claims 18 and 19, claim 160 recites wherein the modified IgG comprises an Fc constant region having a CH2 or CH3 domain or a combination thereof.
Regarding claim 20, 161 recites wherein the wild-type feline IgG constant domain comprises the amino acid sequence set forth in SEQ ID NO: 3, which is 100% identical to instant SEQ ID NO: 1.
Regarding claim 72, claim 162 recites a pharmaceutical composition comprising the modified IgG of claim 155 and a pharmaceutically acceptable carrier.
Regarding claim 73, claim 163 recites a kit comprising the modified IgG in a container and instructions for use.
Thus, although the claims are directed towards a genus of feline IgG mutations comprising a 434 to histidine mutation and a further mutation at position 428, this genus comprises the obvious variant comprising an IgG with S428F because the definition of a mutation at position 428 in the ‘725 specification includes the substitution to F which increases FcRn binding.
Claims 12, 14, 15, 18-20, 72, and 73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 145-158 of copending Application No. 18640470 in view of U.S. 20220009994 to Brondyk et. al. effectively filed 10 July 2020; WO2020082048 A1 to Zhan et. al. published 23 April 2020; and U.S. 20080287657 to Hinton et. al published 20 November 2008.
This is a provisional nonstatutory double patenting rejection.
The claims of ‘470 recite a method for increasing the serum half-life of a feline IgG in a cat (claim 155) and a composition of a feline IgG comprising a mutant feline IgG constant domain and a feline IgG variable domain (claim 151), wherein the mutant feline IgG constant domain comprises the amino acid substitution of serine at position 434 with histidine
Thus, the main difference between the claims of ‘470 and the instant application is that the claims of ‘470 do not recite a substitution at position 428 to phenylalanine (F).
This deficiency is resolved by Brondyk et. al., Zhan et. al., and Hinton et. al.
The teachings of Brondyk et. al., Zhan et. al., and Hinton et. al. are in the 103 rejection above and are incorporated by reference herein. In particular, Brondyk et. al. and Zhan et. al. teach feline IgG domains comprising mutations that increase affinity to FcRn wherein positions 434, 436, 438, 440, 259, and 308 have wildtype residues (e.g. a mutation at residue 311). Brondyk et. al. additionally teaches a substitution at position 434 including S434H [0024].
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to substitute 428F mutation that had not yet been tried by Brondyk et. al. in the feline IgG domain of ‘470 in combination with the 434H mutation in order to increase the affinity of the IgG for FcRn as taught by Brondyk et. al. and Zhan et. al. This would have a reasonable expectation of success 1) ‘470, Brondyk et. al., and Zhan et. al. both teach combinations of mutations at positions in a feline Fc domain that increase feline Fc binding to feline FcRn; 2) Brondyk et. al., and Zhan et. al. all teach mutations at position 248 that increase or do not decrease the binding of feline Fc to feline FcRn when it is the only mutation; 3) Brondyk et. al. and Zhan et. al. teach S428W, S428Y, and S428L which would be a conservative mutations to S428F; 4) the human and feline FcRn sequences are 100% identical in this portion of the Fc region and Hinton et. al. teaches that the M428F mutation increases binding to human FcRn. Therefore, a person of ordinary skill in the art would expect to be able to design a Fc region that has increased binding to FcRn for a longer half-life in felines as taught by ‘470, Brondyk et. al., and Zhan et. al. by using the mutations of Brondyk et. al. and Zhan et. al. combined with S428F, which an artisan would expect to either not disrupt Fc/FcRn binding or to improve Fc/FcRn binding based on the teachings of Brondyk et. al., Zhan et. al., and Hinton et. al.
Claims 12, 14, 15, 18-20, 72, and 73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3,-6, 8-18, 20-21, and 24-28 of copending Application No. 18997211 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of '211 anticipate the instant claims.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim interpretation: The instant claims are directed towards a polypeptide comprising: a feline IgG constant domain comprising at least one amino acid substitution relative to a wild-type feline IgG constant domain, wherein said substitution is at amino acid residue 428 numbered according the EU index as in Kabat, and wherein said substitution is S428F. Regarding the definition of a feline IgG constant domain, the instant specification states, “The Fc region of an immunoglobulin generally comprises two constant domains, CH2 and CH3. In some embodiments, variants having one or more of the constant domains are contemplated. In other embodiments, variants without such constant domains (or with only portions of such constant domains) are contemplated”. Thus, the broadest reasonable interpretation of the instant claims is a polypeptide comprising a portion of the feline IgG Fc (reads “constant domain”) comprising at least on substitution relative to a wild-type feline IgG constant domain, wherein said substitution is at amino acid residue 428 numbered according to EU numbering and wherein the substitution is S428F. The examiner notes that, additionally, there is no ceiling on the “or more” substitutions, and therefore the IgG constant domain encompasses IgG domains from virtually any species which comprise additional substitutions relative the feline IgG constant domain.
Regarding claims 12 and 20, The claims of the ‘211 application recite a modified IgG comprising a bovine IgG constant domain comprising at least one amino acid substitution relative to a wild-type bovine IgG constant domain, wherein said substitution is at amino acid residue 252, 286, 311, 312, 426, 428, 434, or 436, numbered according to the EU index as in Kabat, wherein said constant domain comprises at least one of substitutions followed by a list of substitutions including M428F. The ‘211 application teaches the IgG constant domain wherein the wild-type bovine IgG constant domain comprises one of the amino acid sequences set forth in SEQ ID NOs: 1-9 (claim 10). As shown below, the portion of SEQ ID NO: 1 residues 309-329 comprising the 428F mutation is 73.7% identical to residues 315-335 of instant SEQ ID NO: 1 comprising the 428F mutation:
RESULT 1
AASEQ2_03232026_193854
Query Match 73.7%; Score 84; DB 1; Length 21;
Best Local Similarity 71.4%;
Matches 15; Conservative 4; Mismatches 2; Indels 0; Gaps 0;
Qy 1 VFHEALHSHHTQKSLTQSPGK 21
|||||||:|:|||| ::| ||
Db 1 VFHEALHNHYTQKSTSKSAGK 21
Thus, the claims of the ‘211 application read on a portion of a feline IgG constant domain comprising one or more mutations relative to the wildtype feline constant domain.
Regarding claim 14, claim 6 teaches that the IgG domain wherein the modified IgG domain has a marked effect on its affinity to bovine FcRn relative to the affinity of an IgG having the wild-type bovine constant domain and claim 21 recites a method for increasing the binding affinity of IgG to FcRn in a bovine comprising the IgG domain substitutions.
Regarding claims 18 and 19, claim 9 teaches the IgG constant domain having a CH2 and CH3 domain.
Regarding claim 72, claim 11 teaches a pharmaceutical composition comprising the modified IgG and a pharmaceutically acceptable carrier.
Regarding claim 73, claim 12 teaches a kit comprising the modified IgG of claim 1 in a container and instructions for use.
Conclusion
No claims are allowed.
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/KATHLEEN CUNNINGCHEN/ Examiner, Art Unit 1646
/GREGORY S EMCH/ Supervisory Patent Examiner, Art Unit 1678