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 election without traverse of Group I, claims 1-16, and species (a) polypeptide of claim 1 and (b) amino acid substitution at position 286 in the reply filed on August 14, 2026 is acknowledged.
Claims 4-12 and 17-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claim.
Claims 1-3 and 13-16 are under consideration in this office action.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. This application claims benefit to U.S. Provisional Application No. 63/477,267, filed December 27, 2022.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on May 20, 2024 and August 14, 2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the IDSs are being considered by the examiner.
Nucleotide and/or Amino Acid Sequence Disclosures
Summary of Requirements for Patent Applications Filed on Or After July 1, 2022, That Have Sequence Disclosures
37 CFR 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.831(b) must contain a “Sequence Listing XML”, 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 1.831-1.835. This “Sequence Listing XML” part of the disclosure may be submitted:
1. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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”) in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 CFR 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 CFR 1.831(a) using the symbols and format requirements of 37 CFR 1.832 through 1.834 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 statement of the material in the XML format according to 37 CFR 1.52(e)(8) and 37 CFR 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
SPECIFIC DEFICIENCIES AND THE REQUIRED RESPONSE TO THIS NOTICE ARE AS FOLLOWS:
Specific deficiency - Sequence appearing in the drawings is not identified by sequence identifiers in accordance with 37 CFR 1.831(c). In Figure 2, the amino acid sequence for “Human IgG1 Fc” is not identified with a SEQ ID NO in either the drawing or specification. Sequence identifiers for sequences (i.e., “SEQ ID NO:X” or the like) must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Amended 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 (i.e., “SEQ ID NO:X” or the like) 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 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.
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 1-3 and 13-16 are rejected under 35 U.S.C. 103 as being unpatentable over US 20090041770, published February 12, 2009 (“Chamberlain”; IDS from 5/20/2024) in view of US 20220048981, filed December 5, 2019 (“Nakao”; IDS from 5/20/2024) and Booth et al, published October 2018 (see IDS from 5/20/2024; NPL I).
Chamberlain teaches an Fc variant of human IgG comprising both 252Y and 286D ([0019],[0022], Figure 31A), as in the feline IgG variant of instant claims 1-3 where amino acid 252 is Tyr and amino acid 286 is Asp. Mutant 286D was associated with 10.18 times increase in FcRn affinity compared to wildtype (Figure 13d); mutant 252Y/257N was associated with 25.48 times increase in FcRn affinity compared to wildtype (Figure 13d). Chamberlain also teaches that the IgG variant is formulated as a pharmaceutical composition [0217], as in instant claim 16.
Chamberlain (Figure 2) teaches that the amino acid sequence of human IgG1, according to EU numbering, is as follows:
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Chamberlain does not teach the amino sequence of wildtype feline IgG1, as required by instant claim 13. Nakao teaches that feline IgG1 is comprised of SEQ ID NO: 2 [0084], which is identical to instant SEQ ID NO: 1, as in claim 13. Nakao also teaches modifications of feline Fc receptor that enhances FcRn binding activity under acidic conditions (abstract). EU numbering system for human IgG was adapted for the Fc region of cat [0030]. Nakao teaches substitution of position 252 with tyrosine [0014]), as in instant claim 1. Because Nakao teaches the amino acid sequence of feline IgG1 and the numbering for the amino acid sequence of human IgG1 in Chamberlain aligns with that of feline IgG1, as shown in instant Figure 2 (reproduced below), it would have been obvious to the ordinary artisan that the amino acid substitutions at amino acids 252 and 286 of human IgG1 read on instant feline IgG1a.
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Although Chamberlain teaches the two amino acid variants claimed and that each variant individually increased Fc affinity for FcRn, there is no data in Chamberlain regarding the affinity or Kd of an IgG1 Fc with 252Y and 286D mutations. When Chamberlain is considered in view of Booth, however, the elected polypeptide species is obvious. Booth developed a structure- and network-based framework to interrogate the engagement of IgG with multiple Fc receptors simultaneously (abstract), and using this framework, they identified features that govern Fc-FcRn interactions as well as identified multiple distinct pathways for enhancing FcRn binding in a pH-specific manner (abstract). Booth teaches that the Fc mutant M252Y/S254T/T256E mutant is well validated and is known to extend the half life of Fc (pg 1098, column 2, para 1). Booth also teaches that Fc residues T256D, H286D, T307R, Q311V, A378V, and N286 are located on the periphery of the Fc-FcRn interface and, when these residues are mutated to polar amino acids to complement the positively charged N-terminal region of the FcRn, binding affinity for FcRn is enhanced (Table 1, pg 1102, columns 1-2).
Booth teaches that reducing the rate of dissociation (koff) of the Fc-FcRn interaction at acidic pH is a key factor for improving half-life. As such, Booth prioritized the identification of mutations (including 252Y and 286D) that slow koff (pg 1099, column 2, para 1; Table 1), as in claims 14-15.
Given that Chamberlain teaches variants of human IgG1 with enhanced affinity for Fc receptors, the ordinary artisan would apply the mutations of Chamberlain in a feline Fc of Nakao and have a reasonable expectation of success of generating a feline Fc region with improved properties. This is not only because Chamberlain teaches the variant claimed in human IgG1, but because Booth teaches an enabling methodology and rationale for selection of the amino acid substitution at 286 and Chamberlain and Nakao teach that 252Y is a preferred variant that is well validated in the art [0256]. It would be obvious to one of ordinary skill in the art at the time the invention was filed to produce feline IgG Fc variants by performing amino acid substitutions at positions 252 and 286 because one could have mutated the amino acid at the same positions in feline IgG Fc following well-established point mutation methods of Chamberlain, Booth, and Nakao. Such variants would be expected to exhibit the claimed functional characteristics, including enhanced affinity at lower pH values. As stated in MPEP 2143, known work in one field of endeavor may prompt variations of it for use in the same field if the variations are predictable to one of ordinary skill in the art (see MPEP 2143).
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 1-3 and 13-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-28 of U.S. Patent No. 12,103,961 in view of US 20220048981, filed December 5, 2019 (“Nakao”). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to the same amino acid substitution of IgG1 Fc.
Claims 1-2 of ‘961 teach polypeptides comprising porcine IgG Fc region variants with 252Y and 286 D; the amino acid positions are based on EU numbering, as in instant claims 1-3.
‘961 does not teach the amino sequence of wildtype feline IgG1, as required by instant claim 13. Nakao teaches that feline IgG1 is comprised of SEQ ID NO: 2 [0084], which is identical to instant SEQ ID NO: 1, as in claim 13. Nakao also teaches a modification of feline Fc receptor that enhances FcRn binding activity under acidic conditions (abstract). EU numbering system for human IgG was adapted for the Fc region of cat [0030]. Because Nakao teaches the amino acid sequence of feline IgG1, which is based on EU numbering, it would have been obvious to the ordinary artisan that the amino acid substitutions at amino acids 252 and 286 of porcine IgG1 read on instant feline IgG1a.
Given that ‘961 teaches variants based on EU numbering of porcine IgG1 with enhanced affinity for Fc receptors (‘961 claim 1) and that Nakao teaches the feline Fc amino acid sequence and alignment with human IgG1 based on EU numbering, the ordinary artisan would apply the mutations of
‘961 in a feline Fc and have a reasonable expectation of success of generating a feline Fc region with improved properties. This is because ‘961 teaches the variant claimed in porcine IgG1, and it would be obvious to produce feline IgG Fc variants by performing amino acid substitutions at the same positions of 252 following well-established point mutation methods of Nakao. Such variants would be expected to exhibit the claimed functional characteristics, including enhanced affinity at lower pH values. As stated in MPEP 2143, known work in one field of endeavor may prompt variations of it for use in the same field if the variations are predictable to one of ordinary skill in the art (see MPEP 2143).
Claims 1-3 and 13-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11,542,333 in view of US 20220048981, filed December 5, 2019 (“Nakao”). Although the claims at issue are not identical, they are not patentably distinct from each other because they are both drawn to the same amino acid substitution of IgG1 Fc.
Claims 1-2 of ‘333 teach polypeptides comprising canine IgG Fc region variants with 252Y and 286 D; the amino acid positions are based on EU numbering, as in instant claims 1-3.
‘333 does not teach the amino sequence of wildtype feline IgG1, as required by instant claim 13. Nakao teaches that feline IgG1 is comprised of SEQ ID NO: 2 [0084], which is identical to instant SEQ ID NO: 1, as in claim 13. Nakao also teaches a modification of feline Fc receptor that enhances FcRn binding activity under acidic conditions (abstract). EU numbering system for human IgG was adapted for the Fc region of cat [0030]. Because Nakao teaches the amino acid sequence of feline IgG1, which is based on EU numbering, it would have been obvious to the ordinary artisan that the amino acid substitutions at amino acids 252 and 286 of canine IgG1 read on instant feline IgG1a.
Given that ‘333 teaches variants based on EU numbering of canine IgG1 with enhanced affinity for Fc receptors (‘333 claim 1) and that Nakao teaches the feline Fc amino acid sequence and alignment with human IgG1 based on EU numbering, the ordinary artisan would apply the mutations of
‘333 in a feline Fc and have a reasonable expectation of success of generating a feline Fc region with improved properties. This is because ‘333 teaches the variant claimed in canine IgG1, and it would be obvious to produce feline IgG Fc variants by performing amino acid substitutions at the same positions of 252 and 286 following well-established point mutation methods of Nakao. Such variants would be expected to exhibit the claimed functional characteristics, including enhanced affinity at lower pH values. As stated in MPEP 2143, known work in one field of endeavor may prompt variations of it for use in the same field if the variations are predictable to one of ordinary skill in the art (see MPEP 2143).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER BENAVIDES whose telephone number is (571)272-0545. The examiner can normally be reached M-F 9AM-5PM (EST).
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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.
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Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675
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