DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2 Applicant's amendment, filed on 06/30/2026, is acknowledged.
3. Claims 30-42 are pending and under examination.
4. Applicant’s IDS, filed 06/30/2026, is acknowledged.
5. 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.
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6. Claims 30-42 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 11591386 B2 (IDS #2). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the `386 patent are directed to methods of inhibiting classical pathway of complement activation in a subject, comprising administering to a subject in need thereof an effective amount of a monoclonal antibody or antigen-binding fragment thereof that specifically binds to human complement factor C2, wherein said monoclonal antibody or fragment thereof comprises: a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 3; and a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 2, wherein the autoimmune disease is selected from the group consisting of allergic neuritis; type II collagen-induced arthritis; myasthenia gravis; hemolytic anemia; glomerulonephritis; idiopathic membranous nephropathy; rheumatoid arthritis; systemic lupus erythematosus; immune complex-induced vasculitis; adult respiratory distress syndrome; stroke; xenotransplantation; allotransplantation; multiple sclerosis; burn injuries; extracorporeal dialysis and blood oxygenation; inflammatory disorders, including sepsis and septic shock; toxicity induced by in vivo administration of cytokines or monoclonal antibodies; antibody-mediated rejection of allografts such as kidney allografts; multiple trauma; ischemia-reperfusion injuries; and myocardial infarction.
The claims of the `386 patent anticipate the claimed invention.
Applicant’s arguments, filed 06/30/2026, have been fully considered, but have not been found convincing.
Applicant submits that claims 30-41 are patentably distinct from claims of the `386 patent.
This not found persuasive because the
claims of the `386 patent are directed to methods of inhibiting classical pathway of complement activation in a subject, comprising administering to a subject in need thereof an effective amount of a monoclonal antibody or antigen-binding fragment thereof that specifically binds to human complement factor C2, wherein said monoclonal antibody or fragment thereof comprises: a VH domain comprising the amino acid sequence set forth in SEQ ID NO: 3; and a VL domain comprising the amino acid sequence set forth in SEQ ID NO: 2, wherein the autoimmune disease is selected from the group consisting of allergic neuritis; type II collagen-induced arthritis; myasthenia gravis; hemolytic anemia; glomerulonephritis; idiopathic membranous nephropathy; rheumatoid arthritis; systemic lupus erythematosus; immune complex-induced vasculitis; adult respiratory distress syndrome; stroke; xenotransplantation; allotransplantation; multiple sclerosis; burn injuries; extracorporeal dialysis and blood oxygenation; inflammatory disorders, including sepsis and septic shock; toxicity induced by in vivo administration of cytokines or monoclonal antibodies; antibody-mediated rejection of allografts such as kidney allografts; multiple trauma; ischemia-reperfusion injuries; and myocardial infarction.
7. Claims 30-35, 37, 39-42 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims of U.S. Patent No. 9944717 (IDS # A1) in view of US 20030054497. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the `717 patent are directed to methods for treating an individual suffering from excessive or over-active complement activity, said method comprising administering to an individual in need thereof the antibody no. 5F2.4-VL3 of SEQ 101 and VH4, SEQ 106 that are 100% and 99% identical to claimed SEQ ID NO: 2 and 3, respectively. methods for treating an individual suffering from or at risk of suffering from an inflammatory disease, a neurological disease or ischemia-reperfusion (I/R) injury, said method comprising administering to an individual in need thereof 5F2.4-VL3 of SEQ ID NO: 101 and VH4 of SEQ ID NO: 106, wherein said individual is suffering from antibody-mediated inflammation or ischemia-reperfusion injury.
The claims of the `717 patent differ from the instant claims only in that SEQ ID NO: 3 is 99% identical to patented SEQ ID NO: 106, wherein a glycosylation site was removed by site-directed mutagenesis to generate an N72D variant which resulted in claimed VH of SEQ ID NO: 3.
Alignment of claimed SEQ ID NO: 3 with issued SEQ ID NO: 106.
Qy 1 EVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNMDWVRQATGQGLEWIGDINPNYESTGY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNMDWVRQATGQGLEWIGDINPNYESTGY 60
Qy 61 NQKFKGRATMTVDKSISTAYMELSSLRSEDTAVYYCAREDDHDAFAYWGQGTLVTVSS 118
||||||||||||:|||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQKFKGRATMTVNKSISTAYMELSSLRSEDTAVYYCAREDDHDAFAYWGQGTLVTVSS 118
The `497 publication provides methods for producing mutated immunoglobulins, particularly mutated monoclonal antibodies that have an increased affinity and/or a modified specificity for binding an antigen, wherein the modification of the antigen binding property results from an introduction of at least one mutation in an immunoglobulin chain variable region (V region) that changes the pattern of glycosylation in the V region. Such mutations may add a novel glycosylation site in the V region, change the location of one or more V region glycosylation site(s), or preferably remove a pre-existing V region glycosylation site, more preferably removing an N-linked glycosylation site in a V region framework, and most preferably removing an N-linked glycosylation site that occurs in the heavy chain V region framework in the region spanning about amino acid residue 65 to about amino acid residue 85, using the numbering convention of Co et al. (1992). A preferred method introduces V region mutations that increase the antibody affinity for specific antigen [0010], [0067] (published claims 11-21). The `497 publication teaches that the glycosylation site sequence for N-linked glycosylation is: -Asn-X-Ser- or -Asn-X-Thr-, where X may be any of the conventional amino acids, other than proline. Affinity for binding a pre-determined polypeptide antigen can generally be increased by introducing mutations into the V region framework, typically in areas adjacent to one or more CDRs and/or in a framework region spanning from about amino acid residue 65 to about amino acid residue 85, so that one or more, preferably all, pre-existing glycosylation site sequences are removed. A mutation is adjacent to a CDR if it is within about 5 to 10 amino acids of a CDR-framework boundary, typically within 8 amino acids of a CDR-framework boundary. Typically, such mutation(s) involves the introduction of conservative amino acid substitutions that destroy the glycosylation site sequence(s) but do not substantially affect the hydropathic structural properties of the polypeptide [0038]. The `497 teaches that the conservative substitution is intended combinations such as , for example Asp [0033].
Given that the 5F2.4 VH of referenced SEQ ID NO: 106 contain N-liked glycosylation motif NKS/-Asn-X-Ser- in the framework in the region spanning about amino acid residue 65-85, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce a mutation that removes the glycosylation site at position N72 in the parent VH of SEQ ID NO: 106 by changing Asn to Asp to increase the antibody affinity for specific antigen.
9. 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.
9. Claims 30-33, 35, 39-42 are rejected under 35 U.S.C. 103 as being unpatentable over WO2014189378-A1 (IDS # B9) in view of US 20030054497.
The `378 publication teaches antibody binding molecule that bind to human complement factor C2 and uses thereof in the treatment or prevention complement activation mediated diseases or disorders, such as antibody-mediated inflammatory diseases and ischemia-reperfusion (I/R) injury in ischemic conditions (abstract) and autoimmune diseases (see page 25, 1st ¶).
The `378 publication teaches humanized anti-complement C2 antibody no. 5F2.4-VL3 of SEQ 101 and VH4, SEQ 106 that are 100% and 99% identical to claimed SEQ ID NO: 2 and 3, respectively, for treating an inflammatory disease, a neurological disease, or from antibody-mediated inflammation or ischemia-reperfusion injury, such as acute myocardial infarction, stroke, sepsis, immune complex diseases, rheumatoid arthritis, systemic lupus erythematosus, vasculitis, multiple trauma, multifocal motor neuropathy, antibody-mediated rejection of a renal allograft, (auto)immune hemolytic anemia, cardiopulmonary bypass and other vascular surgery, idiopathic membranous nephropathy, Goodpasture's syndrome. The present sequence is a humanized anti-complement C2 monoclonal antibody no. 5F2.4 heavy chain variable region (VH) 5F2.4-VH4, useful for preparing the binding molecule or antibody for treating an individual suffering from excessive or overactive complement activity (see claims 12-14), wherein the diseases are human disease (abstract). The `878 publication teaches full-length monoclonal antibody comprising humanized IgG4 chain 5F2.4 (see page 7, lines 18+) or IgG1 antibody (page 13, lines 7+). The `378 publication teaches a human IgG1 mutated in the constant region to reduce or prevent complement activation or Fc receptor interactions, or a human IgG4, or a human IgG4 mutated to prevent the exchange of half-molecules with other IgG4 molecules and/or mutated in the constant region to reduce or prevent Fc receptor.interactions..
The published antibody would compete with the claimed antibody because both antibodies are derive from the mAb 5F2.4 and bind C2b and share the same CDRs.
Claim 35 is included because under Example 11 at page 54 of the `378 teaches the generation of chimeric human IgG1̝κ and/or human IgG4κ anti-C2-5F2.4 antibody.
Alignment of claimed SEQ ID NO: 2 with referenced SEQ ID NO: 101, 117.
Qy 1 DNVLTQSPDSLAVSLGERATISCRASKSVRTSGYNYMHWYQQKPGQPPKLLIYLASNLKS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DNVLTQSPDSLAVSLGERATISCRASKSVRTSGYNYMHWYQQKPGQPPKLLIYLASNLKS 60
Qy 61 GVPDRFSGSGSGTDFTLTISSLQAEDAATYYCQHSRELPYTFGQGTKLEIK 111
|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GVPDRFSGSGSGTDFTLTISSLQAEDAATYYCQHSRELPYTFGQGTKLEIK 111
Alignment of claimed SEQ ID NO: 3 with published SEQ ID NO: 106.
Qy 1 EVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNMDWVRQATGQGLEWIGDINPNYESTGY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVQSGAEVKKPGASVKVSCKASGYTFTDYNMDWVRQATGQGLEWIGDINPNYESTGY 60
Qy 61 NQKFKGRATMTVDKSISTAYMELSSLRSEDTAVYYCAREDDHDAFAYWGQGTLVTVSS 118
||||||||||||:|||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQKFKGRATMTVNKSISTAYMELSSLRSEDTAVYYCAREDDHDAFAYWGQGTLVTVSS 118
The reference teachings differ from the claimed invention only in that the glycosylation site was removed by site-directed mutagenesis to generate an N72D variant of the VH of SEQ ID NO: 3.
The `497 publication provides methods for producing mutated immunoglobulins, particularly mutated monoclonal antibodies that have an increased affinity and/or a modified specificity for binding an antigen, wherein the modification of the antigen binding property results from an introduction of at least one mutation in an immunoglobulin chain variable region (V region) that changes the pattern of glycosylation in the V region. Such mutations may add a novel glycosylation site in the V region, change the location of one or more V region glycosylation site(s), or preferably remove a pre-existing V region glycosylation site, more preferably removing an N-linked glycosylation site in a V region framework, and most preferably removing an N-linked glycosylation site that occurs in the heavy chain V region framework in the region spanning about amino acid residue 65 to about amino acid residue 85, using the numbering convention of Co et al. (1992). A preferred method introduces V region mutations that increase the antibody affinity for specific antigen [0010], [0067] (published claims 11-21). The `497 publication teaches that the glycosylation site sequence for N-linked glycosylation is: -Asn-X-Ser- or -Asn-X-Thr-, where X may be any of the conventional amino acids, other than proline. Affinity for binding a pre-determined polypeptide antigen can generally be increased by introducing mutations into the V region framework, typically in areas adjacent to one or more CDRs and/or in a framework region spanning from about amino acid residue 65 to about amino acid residue 85, so that one or more, preferably all, pre-existing glycosylation site sequences are removed. A mutation is adjacent to a CDR if it is within about 5 to 10 amino acids of a CDR-framework boundary, typically within 8 amino acids of a CDR-framework boundary. Typically, such mutation(s) involves the introduction of conservative amino acid substitutions that destroy the glycosylation site sequence(s) but do not substantially affect the hydropathic structural properties of the polypeptide [0038]. The `497 teaches that the conservative substitution is intended combinations such as , for example Asp [0033].
Given that the 5F2.4 VH of referenced SEQ ID NO: 106 contain N-liked glycosylation motif NKS/-Asn-X-Ser- in the framework in the region spanning about amino acid residue 65-85, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce a mutation that removes the glycosylation site at position N72 in the parent VH of SEQ ID NO: 106 by changing Asn to Asp to increase the antibody affinity for specific antigen.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
10. Claims 34 and 37 are rejected under 35 U.S.C. 103 as being unpatentable over WO2014189378-A1 (IDS # B9) in view of US 20030054497, as applied to claims 30-33, 35, 39-42 and further in view of US 20160083440.
The teachings of the `378 and `497 publications have been discussed, supra.
The reference teachings differ from the instant claims only in the recitation that the VH comprising the human constant region of IgG1 of SEQ ID NO: 4 comprising "H433K/N434F" mutations in claim 34
The `440 publication teaches a suitable Fc domain comprises one or more mutations that improve binding between the Fc domain and the FcRn receptor resulting in prolonged serum half-life. A suitable Fc domain contains mutations H433K (His433Lys) and/or N434F (Asn434Phe). A suitable Fc domain comprises a sequence shown below which incorporates the mutations of H433K (His433Lys) and N434F (Asn434Phe) [0014] [0029], [0137].
Claim 37 is included because the `387 publication teaches anti-complement C2 mAb no. 5F2.4 kappa light chain VL1, SEQ 117 that is 100% identical to claimed SEQ ID NO: 7. Further, the resultant VH the combined reference teachings of `378 publication and `497 publication in combination with the teachings of the `440 would result in claimed SEQ ID NO: 6.
Those of skill in the art would have had a reason to introduce "H433K/N434F" mutation in human IgG1 constant region of the VH taught by the `378 publication to improve binding between the Fc domain and the FcRn receptor resulting in prolonged serum half-life.
11. SEQ ID NO: 5 and SEQ ID NO: 8 are free from prior art.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to MAHER M HADDAD whose telephone number is (571)272-0845. The examiner can normally be reached on Monday-Friday from7:00AM to 4:30PM. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu, can be reached at telephone number 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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July 29, 2026
/MAHER M HADDAD/ Primary Examiner, Art Unit 1644
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