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 .
Restriction/Election
Applicant’s election without traverse of Group I, drawn to an Fc monomer peptide comprising CH2 and CH3, isolated CH3 domain, fusion and associated pharmaceutical composition and kit and corresponding to claims 1-10, 14-15, and 17-20 in the reply filed 04/30/2026 is acknowledged.
Applicant has further elected examination of the following species: (a) Fc monomer peptide - SEQ ID NO:2 and (b) fusion partner – heterologous protein.
Claim Status
Claims 1-20 are pending. Claims 11-13 and 16 are withdrawn for being directed to non-elected inventions. Claims 3-5, 9-10, and 19 are withdrawn for being directed to withdrawn species.
Claims 1-2, 6-8, 14-15, 17-18, and 20 are under examination.
Claim Objections
The following claims are objected to for minor informalities:
Claim 1 is objected to for missing “(1)” after “wherein” in Line 2.
Claims 8 and 16 are objected to for line 4, “a target binding region thereof fusion”.
Appropriate correction is required.
Improper Markush Rejection
Claims 1 and 6-8, 14-15, 17-18, and 20 are rejected on the basis that they contain an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of claims 1 and 6 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
Regarding claim 1, the listing of alternatives comprises: (1) 62 IgG1 Fc variants comprising six mutations in the CH3 Fc region compared to the native Fc, (2) an additional IgG1 Fc variant set forth in SEQ ID NO:2 with 6 mutations in the CH3 Fc region compared to the native Fc, and (3) IgG2, IgG3 and IgG4 each comprising 4 amino acid mutations in their CH3 Fc region compared to the native Fc. While the different IgG subclasses share some sequence similarity, they differ functionally. As an example, each IgG subclass binds the receptors FcγR and FcRn with different strengths resulting in different downstream immunological effects. Therefore, each of the embodiments listed in claim 1 are not functionally interchangeable.
Regarding claim 6, the listing of alternatives comprises: (1) 62 IgG1 CH3 variants comprising six mutations from the native Fc, (2) an additional IgG1 Fc variant set forth in SEQ ID NO:2 with 6 mutations from the native Fc, (3) and IgG2, IgG3 and IgG4 each comprising four amino acid mutations from their native Fc. While the different IgG subclasses share some sequence similarity, they differ functionally. As an example, each IgG subclass binds the receptors FcγR and FcRn with different strengths resulting in different downstream immunological effects. Therefore, each of the embodiments listed in claim 6 are not functionally interchangeable.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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 6, 17-18, and 20 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of copending Application No. 18/260,303 in view of Ying (J Biol Chem. 2013 Aug 30;288(35):25154-25164).
Regarding instant claim 6, pertaining to an isolated CH3 domain comprising amino acids at positions 113-217 in the amino acid sequence of SEQ ID NO:2, ‘303 SEQ ID NO:2 comprises the amino acids at positions 113-217 in the amino acid sequence of SEQ ID NO:2 (‘303 claim 5).
Regarding instant claim 17, pertaining to a fusion comprising a fusion partner connected to the N-terminus and/or C-terminus of the peptide chain of the isolated CH3 domain according to claim 6, ‘303 claim 1 discloses an IL-15 fusion protein and ‘303 claim 5 discloses the IL-15 fusion protein comprises the CH3 domain of the instant SEQ ID NO:2.
Regarding instant claim 18, wherein the fusion partner is a heterologous protein, the instant specification teaches the heterologous protein can be a cytokine and ‘303 teaches the fusion protein comprises an IL-15 variant (‘303 claim 1).
Regarding instant claim 20, pertaining to a pharmaceutical composition comprising the CH3 domain according to claim 6 and a physiologically or pharmaceutically acceptable carrier, ‘303 claim 11 teaches a pharmaceutical composition comprising the fusion protein.
Application ‘303 does not teach the CH3 domain is an isolated CH3 domain.
This deficiency is taught by Ying.
The disclosure of Ying is directed to the generation of a soluble monomeric CH3 domain. The researchers hypothesized that the isolated CH3 could be engineered to functionally mimic full-sized Ig, but with decreased size and increased tissue penetration (Abstract). Ying teaches successful generation of stable and functional fusion comprising an antibody binding domain fused to the isolated CH3 (Fig. 7).
It would have been prima facie obvious to one having ordinary skill in the art at the time of filing to isolate the CH3 domain of ‘303 as taught by Ying. One would have been motivated to do so because Ying teaches isolated CH3 fusions maintain FcRn binding required for half-life extension of the fusion while providing therapeutically significant benefits such as better tissue penetration, better access to sterically restricted epitopes (Pg. 25163, Left column, Full paragraph 1, Lines 1-8) and manufacturing benefits such as higher molar quantities per gram of product and reduced overall manufacturing cost (Pg. 25163, Left column, Full paragraph 2, Lines 25-29). There would be an expectation of success in generating an isolated CH3 of the Fc region of ‘303 and using the isolated CH3 in a fusion protein with a heterologous binding partner because Ying teaches the ability to generate stable isolated CH3 and the variant of ‘303 could readily be generated as taught by Ying using methods widely used in the art at the time of filing.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 1, 6-8, 14-15, 17-18, and 20 are rejected.
Claim 2 is objected to for being dependent on a rejected claim.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CAROL ANN CHASE whose telephone number is (571)270-0934. The examiner can normally be reached Monday-Friday 9:00am-6:00pm.
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/CAROL ANN CHASE/Examiner, Art Unit 1646
/HONG SANG/Primary Examiner, Art Unit 1646
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