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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3 April 2026 has been entered.
Response to Amendment
The amendment filed 4/3/2026 is acknowledged. Claim 1 is amended. Claims 49-52 are new.
Election/Restrictions
As noted in the non-final office action dated 8/7/2025, the response to the restriction/election requirement filed 2 July 2025 is acknowledged. Applicant elects Group I, claims 1, 2, 25, 26, 28, 29, 31, 33-38 drawn to variant polypeptides comprising a human IgG1 Fc domain including an amino acid substitution at one or more positions in the human IgG1 domain from positions 217, 228, 229, 243, 262, 273, 274, 288, 290, 298, 305, 309, 310, 321, 326, 344, 353, 356, 363, 364, 368, 375, 388, 389, 390, 397, 398, 399, 401, 405, 407, 409, 410, 413 424, 438, and 442 by numbering of the EU index as in Kabat; nucleic acids encoding the polypeptides, host cells, or vectors comprising the nucleic acids, compositions comprising the polypeptides and a pharmaceutical carrier, and kits comprising the polypeptides. Additionally, Applicant provisionally elects P228K as a species of specific mutation. Both elections are made without traverse.
Claims 9, 10, 17, 18, 39, 41, and 45 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2 July 2025.
Applicant has canceled the elected species P228K; applicant has further canceled the species rejoined by the examiner P217R. Therefore, for the purposes of expedited prosecution, the Examiner has rejoined the species F405E. Claim 52 is withdrawn as not directed to any of the elected or rejoined species, there being no generic or linking claim.
Claim Status
Claims 1-2, 9, 10, 17, 18, 25, 26, 28, 29, 31, 33-39, 41, 45, and 49-52 are pending. Claims 9, 10, 17, 18, 39, 41, 45, 52 are withdrawn as described in the Election/restriction section above. Claims 1-2, 25, 26, 28-29, 31, 33-38, and 49-51 are under examination in the instant office action.
Withdrawal of Rejections
The rejection of claims 1, 2, 25, 26, 28-29, 31, and 33-37 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 10106624 B2 to Moore et. al published 23 October 2018 (Of record, cited in IDS 2/24/2022) is withdrawn in view of the amendments to the claims.
The rejection of claim 38 is rejected under 35 U.S.C. 103 as being unpatentable over US 10106624 B2 to Moore et. al published 23 October 2018 (Of record, cited in IDS 2/24/2022) is withdrawn in view of the amendment to the claims.
Claim Rejections - 35 USC § 102- New, necessitated by amendment
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 49 and 51 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 10106624 B2 to Moore et. al published 23 October 2018 (Of record, cited in IDS 2/24/2022).
As noted above, due to the cancellation of elected species P228K, the examiner has previously rejoined species P217R.
Regarding claims 49 and 51, Moore et. al. teaches “novel immunoglobulin compositions that co-engage at least two antigens” (Abstract, reads on antibody comprising the variant polypeptide) comprising protein variants of the human Fc region of IgG1 wherein the constant domain comprises the mutation P217R ([14], [127], Claim 1) numbering according to the EU index as in Kabat [64]. Moore et. al. teaches that the immunoglobulin compositions may be antibodies ([35-40], [84-97]) or fusion proteins ([50], [104-[106]). Moore et. al. teaches that the IgG1 Fc may comprise additional Fc substitutions including 252Y/254T/256E and 428L/434S in order to increase FcRn binding at pH 6.0 or serum half-life ([18], Fig. 34, [34], [141], [182]).
Claim(s) 1, 25, 26, 28, 31, 33-38, and 49 are rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by U.S. 20180371086 to Cihlar et. al. published 27 December 2018.
As described above, in the interest of expedited prosecution, the Examiner has rejoined species F405E.
Regarding claims 1, 25, 26, 28, and 49, Cihlar et. al. teaches a gp120 x CD3 bispecific antibody (e.g. Duobodies ®), wherein the bispecific antibodies comprises an IgG1 Fc domain comprising an F405E mutation (See e.g. [0244-0247], [0274]).
Regarding claim 31, the instant specification defines an Fc fusion protein as “As used herein, an "Fc fusion protein" refers to a protein wherein one or more polypeptides are operably linked to an Fc domain […] An Fc fusion comprises an Fc domain of an immunoglobulin (e.g., Fc domain of IgG1) that is operably linked to a polypeptide, such as a receptor, an adhesion molecule, a ligand, an enzyme, a cytokine, or some other protein domain, wherein the polypeptide is capable of binding to a particular target (e.g., a ligand, a receptor, a substrate etc.)”. The bispecific antibodies of Cihlar read on Fc fusion proteins because they including a peptide (e.g. an scFv) fused to the IgG1 domains (e.g. “IgG-like molecules with complementary CH3 domains to force heterodimerization; IgG fusion molecules, wherein full length IgG antibodies are fused to extra Fab fragment or parts of Fab fragment; Fc fusion molecules, wherein single chain Fv molecules or stabilized diabodies are fused to heavy-chain constant-domains” [0241]).
Regarding claims 33-36, Cihlar teaches nucleic acids encoding the antibodies of the invention, including the heavy chain which includes the Fc domain (e.g. [0062]) and host cells comprising the nucleic acids (e.g. [0063]).
Regarding claim 37, Cihlar teaches pharmaceutical composition comprising the antibody an a pharmaceutically acceptable carrier [0080] and wherein the antibody is conjugated to a drug [0276].
Regarding claim 38, Cihlar teaches kits comprising the antibody and “Optionally associated with such container(s) can be a notice in the form prescribed by a governmental agency regulating the manufacture, use or sale of pharmaceuticals or biological products, which notice reflects approval by the agency of manufacture, use or sale for human administration” ([0365]; emphasis is the Examiner’s, reads on instructions for use). Also see MPEP §2112.01.III regarding written instructions.
Claim Rejections - 35 USC § 103- New, necessitated by amendment
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 2, 29, 49, and 50 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. 20180371086 to Cihlar et. al. published 27 December 2018.
The teachings of Cihlar in regard to claims 1 and 25 are in the 102 rejection above.
Regarding claims 2, 49, and 50, Cihlar does not explicitly teach the antibody or Fc fusion protein comprising the F405E mutation and the LS mutation.
Regarding claims 2, 49, and 50, Cihlar teaches “In certain embodiments, the antibodies comprise the L234F, L235E, D264A, M428L, and N434S mutations along with one further mutation selected from the group consisting of F405L, F405A, F405D, F405E, F405H, F405I, F405K, F405M, F405N, F405Q, F405S, F405T, F405V, F405W, and F405Y […] The LS mutations increase the pharmacokinetic half-life of the antibody” ([0244], [0274]).
Regarding claim 29, Cihlar teaches variants of the antibody that have been shown to have differential relative binding for FcRn at pH 6.0/7.0 compared to wildtype and that antibodies comprising LS mutations in the Fc portion that interacts with FcRn showed a significant improvement in FcRn binding at pH 6.0 with lesser impact on binding at a neutral pH of 7.0 in order to provide a prolonged half-life [0380] (reads on increased affinity to FcRn at pH 6.0); instant SEQ ID NO: 1 is a wild-type human IgG1 Fc domain.
It would have been obvious, at the time of filing, for a person of ordinary skill in the art to choose an Fc domain comprising the M428L and N434S mutations along with the further mutation F405E selected from the group of mutations recited at position 405 as taught by Cihlar et. al. in order to benefit from the reduced FcRn function of the LS mutations in the bispecific antibody as taught by Cihlar. This would have a reasonable expectation of success because Cihlar teaches that the mutations F405L, F405A, F405D, F405E, F405H, F405I, F405K, F405M, F405N, F405Q, F405S, F405T, F405V, F405W, and F405Y are art-recognized equivalents all suitable for use in the bispecific antibody at position 405 paired with a 409 mutation on the opposite chain [0029] and explicitly recites combining the LS mutations with one of the group including F405E in order to increasing binding affinity to FcRn at pH 6.0.
Response to Arguments
Applicant’s arguments dated 4/3/2026 have been fully considered but are not persuasive.
Applicant argues that Moore fails to disclose a variant polypeptide as currently amended in claim 1 because claim 1 is now amended to remove the P217R substitution. This argument is moot in view of the new rejection 102, necessitated by amendment, above. Further, the Examiner notes that, while claim 1 has been amended to remove the P217R mutation, applicant has reintroduced the P217R mutation in new independent claim 49 part b). It is therefore unclear how Applicant intends to expedite prosecution by amendment when the claims still recite this limitation which is taught by Moore. Applicant additionally argues that Moore “fails to teach or suggest a variant polypeptide comprising a human IgG1 Fc domain including an amino acid substitution selected from the group consisting of P217R […]” (Remarks p. 12 ¶2). This is not true, as described in the 102 rejection of Moore et. al., above, which recites the P217R mutation in an Fc domain ([14], [127], Claim 1). Applicant argues that “Moore fails to motivate the skilled artisan to modify the immunoglobulin compositions disclosed therein in the manner claimed. Nor could the skilled artisan could have reasonably predicted that a human IgG1 Fc domain including the claimed amino acid substitutions would exhibit elevated affinity towards FcRn at pH 6.0” (Remarks p. 12 ¶2). This is moot because the 103 rejection of claim 38 is withdrawn due to the amendment of claim 1. However, regarding the new 102 rejection of claims 49 and 51, Moore et. al. explicitly discloses that the Fc domains with pI variants that confer better binding at pH 6 (e.g. [141]). Additionally, the property of binding to FcRn is an inherent property of each Fc binding domain. Applicant is reminded that products of identical composition cannot have mutually exclusive properties. A chemical composition and its properties are inseparable. In re Spada 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01.
Regarding new claims 49-52, Applicant argues that “new claims 49-52 are directed to variant polypeptides comprising the specific mutant human IgG1 Fc domains described in Fig. 4 of the specification as-filed. In particular, claim 49 as well as the claims depending therefrom are directed to novel variant polypeptides exhibiting elevated affinity towards FcRn at pH 6.0, and/or rapidly disassociate from FcRn at pH 7.4 compared to a parent Fc domain (Remarks p. 12 bottom and 13 ¶1). First, the Examiner notes that instant claim 49 does not explicitly recite the property of binding FcRn with a higher affinity at pH 6.0, and that instant claim 49 recites that the polypeptides “include” the mutations, which is interpreted as open language. Thus, these arguments are moot in view of the new 102 and 103 rejections based on Moore and Cihlar, above. Regarding the 102 rejections, the examiner also notes that the discovery of a previously unappreciated property of a prior art composition does not render the old composition patentably new to the discoverer (See MPEP 2112). Regarding the 103 rejections, the Examiner notes that, as described in the 103 rejection above, a person of ordinary skill in the art has a reasonable chance of success at making an IgG1 domain comprising F405E and the LS mutations because F405E is one of a closed group of mutations at position 405 explicitly disclosed for use in the bispecific antibody of Cihlar in combination with the LS mutations, which are explicitly disclosed to increase affinity of the Fc domain for FcRn at pH 6.0. Therefore, there in a reasonable expectation of success in making the Fc domain as described at a person of skill in the art would expect to retain the property of the LS mutations as explicitly disclosed by Cihlar.
Conclusion
No claims are allowed.
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/KATHLEEN CUNNINGCHEN/Examiner, Art Unit 1646
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
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