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 .
Response to Amendment
The Amendment filed 04/01/2026 in which claims 1, 25, 44, and 45 were amended, and claims 2, 11, 14, 15, 21-24 were canceled, has been entered.
Claims 1, 3, 7, 8, 12, 25, 40, 43-45, 47-49, 57-59, 61-64, 66, 67, 69, 70 are currently under examination on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) was submitted on 04/01/2026 after the Nonfinal Office Action mailed on 10/01/2025. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
(Previous rejection, withdrawn as to claims 1-3, 7, 8, 11, 12, 14, 15, 21-24, 40, 43-44, 47-49, 57-59, 61-64, 66, 67, 69, 70) Claims 1-3, 7, 8, 11, 12, 14, 15, 21-24, 40, 43-44, 47-49, 57-59, 61-64, 66, 67, 69, 70 are rejected under 35 U.S.C. 103 as being unpatentable over Benjamin et al. in view of Kuo et al. Prior art of record.
See claims 1-3, 7, 8, 11, 12, 14, 15, 21-24, 40, 43-44, 47-49, 57-59, 61-64, 66, 67, 69, 70 as submitted on 04/01/2026.
The previous rejections of claims 2, 11, 14, 15, 21-24 are moot in view of Applicant’s cancelation of these claims.
Applicant’s amendment to the instant claims filed on 04/01/2026 has overcome the previous rejection to claims 1, 3, 7, 8, 12, 40, 43-44, 47-49, 57-59, 61-64, 66, 67, 69, 70.
(Previous rejection, withdrawn as to claims 25 and 45) Claims 25 and 45 were rejected under 35 U.S.C. 103 as being unpatentable over Benjamin et al. and Kuo et al., as applied to claims 1-3, 7, 8, 11-15, 21-24, 40, 43-44, 47-49, 57-59, 61-64, 66-70, further in view of Lindner et al. Prior art of record.
See claims 25 and 45 as submitted on 04/01/2026.
Applicant’s amendment to the instant claims filed on 04/01/2026 has overcome the previous rejection to claims 25 and 45.
(New rejection, necessitated by amendment as to claims 1, 3, 7, 8, 12, 25, 40, 43-45, 47-49, 57-59, 61-64, 66, 67, 69, 70) Claims 1, 3, 7, 8, 12, 25, 40, 43-45, 47-49, 57-59, 61-64, 66, 67, 69, 70 are rejected under 35 U.S.C. 103 as being unpatentable over Benjamin et al. and Kuo et al. in view of Lindner et al. Prior art of record.
See claims 1, 3, 7, 8, 12, 25, 40, 43-45, 47-49, 57-59, 61-64, 66, 67, 69, 70 as submitted on 04/01/2026.
Regarding claims 1 and 25, it is noted that the only amendment to claim 1 filed on 04/01/2026 recites “an IgG1 antibody that binds to a hemagglutinin of an influenza A virus, wherein the antibody comprises a heavy chain comprising the amino acid sequence as set forth in SEQ ID NO: 9 and a light chain comprising the amino acid sequence as set forth in SEQ ID NO: 10”; and no longer requires a heavy chain constant region comprising an M428L and a N434S mutation. As previously explained, Benjamin et al. already teach the antibody of claim 1 (also referred to as antibody MEDI8852 in instant Specification [page 3]) which is a human IgG1 monoclonal antibody binds to a hemagglutinin protein of an influenza A virus (¶¶ [0111], [0295], [0093]). As previously explained, the antibody of Benjamin et al.’s comprises identical CRDs as the claimed antibody of claim 1. As previously noted, SEQ ID NO: 9 and SEQ ID NO: 10 comprise a heavy chain antibody sequence, and a light chain antibody sequence, respectively, wherein such sequences comprise identical CDRs as those taught by Benjamin et al. Benjamin et al. specifically teach an antibody comprising the following:
a heavy chain comprising HCDR1, HCDR2, and HCDR3 sequences as set forth in SEQ ID NO: 113, SEQ ID NO: 114, and SEQ ID NO: 115, respectively (¶¶ [0109]; [111], [0141]; page 40); which share 100% identity to heavy chain sequences CDR1-3 set forth in SEQ ID NO: 1, SEQ ID NO: 2, and SEQ ID NO: 3 and are also present in SEQ ID NO: 9 in instant application (alignment files of record)
a light chain comprising LCDR1, LCDR2, and LCDR3 sequences as set forth in SEQ ID NO: 118, SEQ ID NO: 119, and SEQ ID NO: 119, respectively (¶¶ [0109]; [111], [0141]; page 40); which share 100% identity to light chain sequences CDR1-3 set forth in SEQ ID NO: 4, SEQ ID NO: 5, and SEQ ID NO: 6 and are also present in SEQ ID NO: 10 in instant application (alignment files of record)
It is noted that instant SEQ ID NO:9 is an amino acid sequence 458 residues long comprising the following:
Amino acids 1-128 comprise instant SEQ ID NO: 7 which denotes heavy chain CDRs 1-3.
Amino acids 129-458 comprise a heavy chain framework.
As per SEQ ID NO: 10, it is noted that instant SEQ ID NO: 10 is an amino acid sequence 210 residues long comprising the following:
Amino acids 1-103 comprise instant SEQ ID NO: 8 which denotes light chain CDRs 1-3.
Amino acids 104-210 comprise a kappa light chain framework.
The sequences of SEQ ID NO: 7 and SEQ ID NO: 8 which comprise amino acid residues 1-128 of SEQ ID NO: 9 and amino acid residues 1-103 of SEQ ID NO: 10, respectively were taught by Benjamin et al. and addressed previously. To reiterate, Benjamin et al. teach a heavy chain variable region comprising an amino acid sequence set forth in SEQ ID NO: 112 which shares 100% sequence identity to SEQ ID NO: 7 and a light chain variable region comprising the amino acid sequence set forth in SEQ ID NO: 117 which shares 100% sequence identity to SEQ ID NO: 8 (alignment files of record).
Kuo et al. were cited for teaching a review the fundamental IgG therapeutic antibodies, including important Fc constant region mutations designed to modulate binding the interaction of IgG antibodies and the FcRn receptor (Abstract, page 1). Kuo et al. further teach common strategies in the art for modulating FcRn-IgG binding affinity and antibody half-life, including an M428L and a N434S mutations in the constant region of the heavy chain termed “LS” (Page 4, 5). Kuo et al. further teach that the introduction of an M428L and a N434S mutations in the constant region of the heavy chain results in improved binding for the neonatal Fc receptor (FcRn) as well as improved serum half-life of the antibody (page 6). Kuo et al.’s teachings demonstrate that improved binding for the neonatal Fc receptor and half-life extension of a therapeutic antibody helps maintain drug therapeutic serum levels and reduce the frequency of administration (page 5).
Neither Benjamin et al. nor Kuo et al. teach amino acids 129-458 of SEQ ID NO: 9 which is a heavy chain framework, nor amino acids 104-210 of SEQ ID NO: 10 which is a light chain framework.
However, Lindner et al. teach human antibody sequences including a heavy chain framework sequence and a kappa light chain framework sequence which comprise amino acids 129-458 of SEQ ID NO: 9 and amino acids 104-210 of SEQ ID NO: 10 respectively as follows:
Amino acids 129-458 of SEQ ID NO: 9 are taught by Lindner et al. GeneBank accession number MH975460 in combination with the mutations M428L and N434S as taught by Kuo et al. which were explained above. See sequence alignment file: “US-17-607-383-9 aa129-458_pep__vs__GenBank MH975460_pep__align.pdf” (file of record.)
Amino acids 104-210 of SEQ ID NO: 10 are taught by Lindner et al. GeneBank accession number MH975601. See sequence alignment file: “US-17-607-383-10 aa104-210_pep__vs__GenBank MH975601_pep__align.pdf” (file of record.)
It would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date, to have combined the sequences taught by Lindner et al. with the antibody sequences comprising the antibody variable regions as taught by Benjamin et al. and Kuo et al. for the benefit of formulating an antibody against influenza A with a human framework having improved affinity or the FcRn as well as improved serum half-life. One of ordinary skill in the art would have been motivated to combine the sequences described above given that the human heavy and light chain framework sequences were known in the art and Benjamin et al. taught the variable light and heavy chain regions. See MPEP 2144.07. The selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
One of ordinary skill in the art would have had a reasonable expectation of success for combining the sequences listed above denoting the heavy and light chain variable regions with the human framework regions wherein the heavy chain framework region comprises the M428L and N434S mutations. There would have been a reasonable expectation of success given that the methods of antibody cloning and mutagenesis are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Accordingly, the teachings of Benjamin et al., Kuo et al. and Lindner et al. meet the limitations of claims 1 and 25.
Regarding claim 3, it is noted that no new limitations were introduced to claim 5 in the amendment filed on 04/01/2026. As previously explained, Benjamin et al. further teach the antibody defined above wherein the antibody neutralizes infection with an influenza A virus (¶¶ [0007], [0163], [0298], Table 2).
Regarding claims 7 and 8, it is noted that no new limitations were introduced to claims 7 and 8 in the amendment filed on 04/01/2026. As previously explained, Benjamin et al. further teach the antibody defined above wherein the antibody neutralizes infection with an influenza A virus, wherein the virus comprises the polymorphism N146D of H1 HA (¶¶ [0302], [0304], Table 5), which includes influenza A virus subtype H1 A/California/7 /09 (H1 N1) per instant Specification (instant Specification page 12). Neutralization of Antibody 12 of influenza A virus subtype H1 A/California/7 /09 occurs with an IC50 fold change of 0.98 (< 2 as recited in claim 8) relative to the HA of a wild type virus (¶ [0299], Table 5).
Regarding claims 12, it is noted that no new limitations were introduced to claim 12 in the amendment filed on 04/01/2026. As previously explained, Benjamin et al. further teach the antibody defined above wherein the antibody is a monoclonal antibody (¶¶ [0091], [0092], [0126], [0295]).
Regarding claim 40, it is noted that no new limitations were introduced to claim 40 in the amendment filed on 04/01/2026. As previously explained, Benjamin et al. further teach a nucleic acid molecule comprising a polynucleotide encoding the antibody defined above (¶ [0096], claim 17).
Regarding claim 43, it is noted that no new limitations were introduced to claim 43 in the amendment filed on 04/01/2026. As previously explained, Benjamin et al. further teach nucleic acid sequences encoding part or all of the light and heavy chains and CDRs (the first nucleic acid molecule comprises a polynucleotide encoding the heavy chain of the antibody of claim 1; and the second nucleic acid molecule comprises a polynucleotide encoding the corresponding light chain of the same antibody, as recited in claim 43) (¶ [0096], claim 17).
Regarding claim 44, as previously explained, Benjamin et al. teach nucleic acid sequences encoding the light and heavy chains as recited in claim 43. Benjamin et al. further teach the following nucleic acid molecules:
a heavy chain variable region SEQ ID NO: 111 encoding an amino acid sequence set forth in SEQ ID NO: 112 comprising the heavy chain CDRs of antibody 12. SEQ ID NO: 112 shares 100% sequence identity to SEQ ID NO:7 in instant application which comprises heavy chain CDR1-3, as explained above (Alignment file of record) (page 40).
a light chain variable region SEQ ID NO: 116 encoding the amino acid sequence set forth in SEQ ID NO: 117 comprising the heavy chain CDRs of antibody 12. SEQ ID NO: 117 shares 100% sequence identity to SEQ ID NO:8 in instant application which comprises light chain CDR4-6, as explained above (Alignment file of record) (page 40).
SEQ ID NO: 111 and SEQ ID NO: 116 in Benjamin et al.’s teachings do not share 100% identity to instant SEQ ID NO: 12 and SEQ ID NO: 13 respectively. However, the nucleic acid sequences in Benjamin et al.’s teachings SEQ ID NO: 111 and SEQ ID NO: 116 are equivalent to instant nucleic acids sequences SEQ ID NO: 12 and SEQ ID NO: 13 because they encode the same amino acid sequences. The translation and alignment files provided are as follows:
Regarding instant SEQ ID NO:12:
SEQ ID NO: 111 translation: “US-15026276-111 translate.pdf” (file of record)
Alignment of SEQ ID NO: 111 translation with instant SEQ ID NO:7: “US-17-607-383-7_pep__vs__US-15026276-111 translated_pep__align.pdf” (file of record)
Regarding instant SEQ ID NO:13:
SEQ ID NO: 116 translation: “US-15026276-116 translate.pdf” (file of record)
Alignment of SEQ ID NO: 116 translation with instant SEQ ID NO:8: “US-17-607-383-8_pep__vs__US-15026276-116 translated_pep__align.pdf” (file of record)
As explained previously, Kuo et al. are cited for teaching an M428L and a N434S mutation in the constant region of the heavy chain which is encoded by the nucleic acid in SEQ ID NO: 12. Specifically, Kuo et al. teach a review the fundamental IgG therapeutic antibodies, including important Fc constant region mutations designed to modulate binding the interaction of IgG antibodies and the FcRn receptor (Abstract, page 1). Kuo et al. further teach common strategies in the art for modulating FcRn-IgG binding affinity and antibody half-life, including an M428L and a N434S mutations in the constant region of the heavy chain termed “LS” (Page 4, 5). Kuo et al. further teach that the introduction of an M428L and a N434S mutations in the constant region of the heavy chain results in improved binding for the neonatal Fc receptor (FcRn) as well as improved serum half-life of the antibody (page 6). Kuo et al.’s teachings demonstrate that improved binding for the neonatal Fc receptor and half-life extension of a therapeutic antibody helps maintain drug therapeutic serum levels and reduce the frequency of administration (page 5).
It would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date, to have included the teachings of Kuo et al. about the M428L and the N434S mutations in the constant region of the heavy chain of antibody 12 as taught by Benjamin et al., for the benefit of improving affinity or the FcRn as well as improving serum half-life of the antibody. One of ordinary skill in the art would have been motivated to introduce an M428L and a N434S mutations in the constant region of the heavy chain of antibody 12 as taught by Benjamin et al. given that improved binding for the neonatal Fc receptor and half-life extension of a therapeutic antibody helps maintain drug therapeutic serum levels and reduce the frequency of administration.
One of ordinary skill in the art would have had a reasonable expectation of success for introducing an M428L and a N434S mutations in the constant region of the heavy chain of antibody 12 as taught by Benjamin et al. given that the methods of antibody cloning and mutagenesis are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
With respect to codon optimization, Benjamin et al. further teach the codon optimization of nucleic acid sequences to improve the efficiency of translation in expression systems (¶ [0088]). Therefore the sequences recited in claim 44 in instant application, SEQ ID NO: 12 and SEQ ID NO: 13, are obvious variants of the sequences taught by Benjamin et al.’s teachings SEQ ID NO: 111 and SEQ ID NO: 116.
Regarding claim 45, as previously explained, Benjamin et al. teach nucleic acid sequences encoding the light and heavy chains as recited in claim 43.
As per SEQ ID NO: 14 in claim 45 which comprises the nucleic acid sequence of a heavy chain of an antibody, it is noted that instant SEQ ID NO: 14 is a nucleotide sequence 1374 base pairs long comprising the following:
Nucleotides 1-384 comprise instant SEQ ID NO: 12 which denotes the nucleotide sequence encoding the heavy chain CDRs 1-3.
Nucleotides 384-1374 comprise a nucleotide sequence encoding the heavy chain framework.
As per SEQ ID NO: 15 in claim 45 which comprises the nucleic acid sequence of a light chain of an antibody, it is noted that instant SEQ ID NO: 15 is a nucleotide sequence 630 base pairs long comprising the following:
Nucleotides 1-309 comprise instant SEQ ID NO:13 which denotes the nucleotide sequence encoding the light chain CDRs 1-3.
Nucleotides 310-630 comprise a nucleotide sequence encoding the light chain framework.
The sequences of SEQ ID NO: 12 and SEQ ID NO: 13 which comprise nucleotides 1-384 of SEQ ID NO: 14 and nucleotides 1-309 of SEQ ID NO: 15 respectively, were addressed above in the discussion of claim 44 and shown to be obvious variants of the sequences taught by Benjamin et al.
Neither Benjamin et al. nor Kuo et al. teach nucleotides 384-1374 of SEQ ID NO:14 which comprise a nucleotide sequence encoding the heavy chain framework, nor do they teach nucleotides 310-630 of SEQ ID NO:15 which comprise a nucleotide sequence encoding the light chain framework.
However, Lindner et al. teach human antibody nucleotide sequences including a heavy chain framework sequence and a kappa light chain framework sequence which comprise nucleotides 384-1374 of SEQ ID NO:14 and nucleotides 310-630 of SEQ ID NO:15 respectively as follows:
Nucleotides 384-1374 of SEQ ID NO:14 are taught by Lindner et al. GeneBank accession number MH975460 in combination with the mutations M428L and N434S as taught by Kuo et al. which were explained above. See sequence file: “Lindner JM et al 2019 GenBank MH975460.pdf” (file of record.)
Nucleotides 310-630 of SEQ ID NO:15 are taught by Lindner et al. GeneBank accession number MH975601. See sequence file: “Lindner JM et al 2019 GenBank MH975601.pdf” (file of record.)
The sequences in Lindner et al.’s teachings do not have 100% identity to instant SEQ ID NO: 14 and SEQ ID NO:15 because instant sequences represent codon optimized sequences of the human sequences taught by Lindner et al. Therefore, the nucleic acid sequences in Lindner et al.’s teachings are equivalent to instant nucleic acids sequences SEQ ID NO:14 and SEQ ID NO:15 because they encode the same amino acid sequences as discussed above (see discussion of claim 25 above). Further, Benjamin et al. teach the codon optimization of nucleic acid sequences to improve the efficiency of translation in expression systems (¶ [0088]). Therefore the sequences recited in claim 45 in instant application, SEQ ID NO:14 and SEQ ID NO:15, are obvious variants of the sequences taught by Lindner et al.
It would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date, to have combined the nucleotide sequences taught by Lindner et al. with the antibody sequences comprising the antibody variable regions as taught by Benjamin et al. and Kuo et al., for the benefit of formulating a nucleotide sequence of an antibody against influenza A with a human framework (constant regions) having improved affinity or the FcRn as well as improved serum half-life. One of ordinary skill in the art would have been motivated to combine the nucleotide sequences described above given that the human heavy and light chain framework sequences as well as the M428L and N434S mutations were known in the art and Benjamin et al. taught the variable regions of the light and heavy chains as well as codon optimization.
One of ordinary skill in the art would have had a reasonable expectation of success for combining the sequences listed above denoting the heavy and light chain variable regions with the human framework regions wherein the heavy chain framework region comprises the M428L and N434S mutations given that the methods of antibody cloning, sequence optimization and mutagenesis are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claim 47, it is noted that no new limitations were introduced to claim 47 in the amendment filed on 04/01/2026. As previously explained, Benjamin et al. teach nucleic acid sequences encoding the light and heavy chains as recited in claim 43. Benjamin et al. further teach a vector comprising isolated nucleic acid sequences encoding the antibody sequences explained above (the combination of nucleic acid molecules of claim 43, as recited in claim 47) (¶ [0097]).
Regarding claim 48, it is noted that no new limitations were introduced to claim 48 in the amendment filed on 04/01/2026. As previously explained, Benjamin et al. further teach a host cell comprising isolated nucleic acid sequences encoding the antibody sequences explained above for expression (a cell expressing, as recited in claim 48) (¶¶ [0098], [0099]).
Regarding claim 49, it is noted that no new limitations were introduced to claim 48 in the amendment filed on 04/01/2026. As previously explained, Benjamin et al. further teach a composition comprising the antibody as explained above and a pharmaceutically acceptable carrier (¶¶ [0100], [0101]).
Regarding claim 57, it is noted that no new limitations were introduced to claim 57 in the amendment filed on 04/01/2026. As previously explained, Benjamin et al. further teach the combination of the antibody as explained above with one or more antiviral medications (¶ [0273]).
Regarding claims 58 and 59, it is noted that no new limitations were introduced to claims 58 and 59 in the amendment filed on 04/01/2026. As previously explained, Benjamin et al. further teach the combination of the antibody as explained above with neuraminidase inhibitors such as zanamivir (RELENZA®) (¶ [0273]).
Regarding claim 61, it is noted that no new limitations were introduced to claim 61 in the amendment filed on 04/01/2026. As previously explained, Benjamin et al. further teach a method of treating influenza A virus infection or delaying influenza A virus infection in a subject comprising administering to a subject in need thereof, a therapeutically effective amount of the antibody as explained above (¶¶ [0270], [0271]).
Regarding claim 62, it is noted that no new limitations were introduced to claim 62 in the amendment filed on 04/01/2026. As previously explained, Benjamin et al. further teach a method of claim 61 wherein the antibody is administered prophylactically (¶¶ [0312], [0195]).
Regarding claim 63, it is noted that no new limitations were introduced to claim 63 in the amendment filed on 04/01/2026. As previously explained, Benjamin et al. further teach a method of claim 61 wherein the antibody is administered prophylactically (¶¶ [0312], [0195]). Benjamin et al. and Kuo et al. in combination teach the antibody of claim 1 comprising the mutations M428L and N434S in the constant region of the heavy chain as explained above. Kuo et al. further teach that the mutations M428L and N434S extended the serum half-life of an antibody in cynomolgus monkey from 9.7 to 31 days, representing a 3.2-fold improvement, which is equivalent to serum half-life of 50 days in humans (page 2). Therefore, the a therapeutically effective (for treatment) dose of an antibody comprising the mutations M428L and N434S is 3.2-fold lower than that of a comparative antibody lacking such mutations.
It would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date, to have included the teachings of Kuo et al. about the improved serum half-life of the antibody comprising the mutations M428L and N434S in the method of prophylactic administration of said antibody as taught by Benjamin et al. One of ordinary skill in the art would have been motivated to reduce the prophylactic dose of the antibody comprising the mutations M428L and N434S by 3.2-fold relative to the dose required for prophylaxis with a comparative antibody which lacks mutations M428L and N434S given that it was known in the art that half-life extension of a therapeutic antibody helps maintain drug therapeutic serum levels and reduce the frequency of administration.
One of ordinary skill in the art would have had a reasonable expectation of success for adjusting the dose of the antibody comprising M428L and N434S mutations. There would have been a reasonable expectation of success given that the methods of prophylactic administration of a composition comprising an antibody are known, successfully demonstrated, and commonly used as evidenced by the applied prior art.
Regarding claim 64, it is noted that no new limitations were introduced to claim 64 in the amendment filed on 04/01/2026. As previously explained, based on the teachings of Benjamin et al. and Kuo et al. discussed above regarding claim 63, the dose of the antibody comprising the mutations M428L and N434S for treatment is 3.2-fold lower than the dose required for treatment with a comparative antibody which lacks mutations M428L and N434S.
Regarding claim 66, it is noted that no new limitations were introduced to claim 66 in the amendment filed on 04/01/2026. As explained above, Benjamin et al. further teach the method of claim 61 wherein a subject is particularly at risk of or susceptible to influenza A virus infection (¶¶ [0270], [0271]). It is noted that instances wherein a subject is particularly at risk of infection encompasses during an influenza epidemic because an epidemic comprises a rapid and widespread outbreak of a disease.
Regarding claim 67, it is noted that no new limitations were introduced to claim 67 in the amendment filed on 04/01/2026. As previously explained, Benjamin et al. further teach the method of claim 61 wherein the antibody as explained above is administered in combination with an antiviral such as a neuraminidase inhibitor (¶ [0273]).
Regarding claims 69 and 70, it is noted that no new limitations were introduced to claims 69 and 70 in the amendment filed on 04/01/2026. Benjamin et al. teach the method of claim 61 wherein the antibody is administered prophylactically (¶¶ [0312], [0195]). Benjamin et al. and Kuo et al. in combination teach the antibody of claim 1 comprising the mutations M428L and N434S in the constant region of the heavy chain as explained above. Kuo et al. further teach that the mutations M428L and N434S extended the serum half-life of an antibody in cynomolgus monkey from 9.7 to 31 days, representing a 3.2-fold improvement, which is equivalent to serum half-life of 50 days in humans (page 2). Therefore, the a therapeutically effective (prophylactic) dose of an antibody comprising the mutations M428L and N434S is 3.2-fold lower than that of a comparative antibody lacking such mutations which represents a decrease in dose by approximately two-thirds, or a decrease of approximately 66.67% (does not exceed half a dose, as recited in claim 69). As to the recitation of “does not exceed one third” in claim 70, it is noted that this range falls within the dose ranges taught by the cited prior art, approximately 30% of the dose with a comparative antibody. Further, a prophylactic and a treatment dose is considered to be one determined by routine optimization according to one of skill in the art in view of the teachings of Benjamin et al. and Kuo 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.
(Previous rejection, withdrawn as to claims 2, 11, 14, 15, maintained and modified as necessitated by amendment as to claims 1, 3, 7, 12, 40, 43, 47-49) Claims 1, 3, 7, 12, 40, 43, 47-49 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 5-14 of U.S. patent No.10494419 to Benjamin et al. (09/08/2016) in view of Kuo et al. and Lindner et al. (previously cited).. Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to a human antibody against the hemagglutinin of an influenza A virus, wherein the antibody neutralizes influenza A infection.
See claims 1, 3, 7, 12, 40, 43, 47-49 as submitted on 04/01/2026.
The previous rejections of claims 2, 11, 14, 15, are moot in view of Applicant’s cancelation of these claims.
As to claims 1, 3, 7, 12, 40, 43, 47-49 of instant application, claims 1-3, 5-14 of U.S. patent No.10494419 are directed to: (a) an antibody against the hemagglutinin of an influenza A virus, where in the antibody comprises the same CDR sequences (see alignment files below), (b) wherein the antibody neutralizes influenza A infection subtype H1, (c) said antibody comprises human constant heavy and light chain region, (d) a vector comprising the nucleic acids encoding said antibody, (e) a cell expressing such vector, and (f) a pharmaceutical composition comprising said antibody.
The two sets of claims indicated above are directed to an antibody comprising CDR sequences with 100% sequence identity as shown in the following alignment files of record:
Heavy chain CDRs:
US-17-607-383-1_pep__vs__US-10-10494419-113_pep__align.pdf
US-17-607-383-2_pep__vs__US-10-10494419-114_pep__align.pdf
US-17-607-383-3_pep__vs__US-10-10494419-115_pep__align.pdf
Light chain CDRs:
US-17-607-383-4_pep__vs__US-10-10494419-118_pep__align.pdf
US-17-607-383-5_pep__vs__US-10-10494419-119_pep__align.pdf
US-17-607-383-6_pep__vs__US-10-10494419-120_pep__align.pdf
Kuo et al. were cited for teaching an IgG1 antibody with an M428L and a N434S mutations in the constant region of the heavy chain (Abstract, page 1). The M428L and the N434S mutations in Kuo et al.’s teachings resulted in 11-fold improved binding for the neonatal Fc receptor (FcRn) as well as improved serum half-life of the antibody (Abstract, page 1, 2). Half-life extension of therapeutic antibody in Kuo et al.’s teachings helps maintain drug therapeutic serum levels and reduce the frequency of administration.
Lindner et al. were cited for teaching a heavy chain framework sequence and a kappa light chain framework sequence which comprise amino acids 129-458 of SEQ ID NO: 9 and amino acids 104-210 of SEQ ID NO: 10, as required by independent claim 1.
It would have been prima facie obvious to a person of ordinary skill in the art, before the effective filing date, to have included the teachings of Kuo et al. about the M428L and the N434S mutations in the constant region of the heavy chain of an antibody and the teachings of Lindner et al. into the claims 1-3, 5-14 of U.S. patent No.10494419, for the benefit of improving affinity or the FcRn as well as improving serum half-life of the antibody. One of ordinary skill in the art would have been motivated to introduce an M428L and a N434S mutations in the constant region of the heavy chain of antibody 12 as taught by claims 1-3, 5-14 of U.S. patent No.10494419. given that half-life extension of a therapeutic antibody helps maintain drug therapeutic serum levels and reduce the frequency of administration.
The sets of claims indicated above differ in scope; instant claims include narrower limitations than those recited in claims 1-3, 5-14 of U.S. patent No.10494419. Instant claims 1, 3, 7, 12, 40, 43, 47-49 are directed to (a) a human monoclonal antibody type IGg1 against the hemagglutinin of an influenza A virus, (b) wherein the antibody neutralizes influenza A infection wherein the influenza virus comprises the polymorphism N146D of influenza subtype H1 NA, (c) a vector comprising the nucleic acids encoding said antibody, (d) a cell expressing such vector, and (e) a pharmaceutical composition comprising said antibody.
A patent to the instant claims would, necessarily, extend the rights of the already patented claims should the instant claims issue as a patent.
(Previous rejection, withdrawn as to claims 2, 11, 14, 15, maintained and modified as necessitated by amendment as to claims 1, 3, 7, 12, 40, 43, 47-49) Claims 1, 3, 7, 12, 40, 43, 47-49 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18, 26, 31-33, 37 of copending application No. 18/255,779 in view of Kuo et al. and Lindner et al. (previously cited). Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are directed to a human antibody against the hemagglutinin of an influenza A virus, wherein the antibody neutralizes influenza A infection. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
See claims 1, 3, 7, 12, 40, 43, 47-49 as submitted on 04/01/2026.
The previous rejections of claims 2, 11, 14, 15, are moot in view of Applicant’s cancelation of these claims.
As to claims 1, 3, 7, 12, 40, 43, 47-49 of instant application, claims 1-18, 26, 31-33, 37 of copending application No. 18/255,779 are directed to: (a) an antibody against the hemagglutinin of an influenza A virus, where in the antibody comprises the same CDR sequences (see alignment files below), (b) wherein the antibody neutralizes influenza A infection, (c) wherein the heavy chain constant region comprises an M428L and a N434S mutation, (d) said antibody comprises human constant heavy and light chain region, (e) a vector comprising the nucleic acids encoding said antibody, (f) a cell expressing such vector, (g) a pharmaceutical composition comprising said antibody, and (h) a method of lowering the risk of influenza A infection comprising administering said antibody.
Kuo et al. were cited for teaching an IgG1 antibody with an M428L and a N434S mutations in the constant region of the heavy chain (Abstract, page 1). The M428L and the N434S mutations in Kuo et al.’s teachings resulted in 11-fold improved binding for the neonatal Fc receptor (FcRn) as well as improved serum half-life of the antibody (Abstract, page 1, 2). Half-life extension of therapeutic antibody in Kuo et al.’s teachings helps maintain drug therapeutic serum levels and reduce the frequency of administration.
Lindner et al. were cited for teaching a heavy chain framework sequence and a kappa light chain framework sequence which comprise amino acids 129-458 of SEQ ID NO: 9 and amino acids 104-210 of SEQ ID NO: 10, as required by independent claim 1.
The two sets of claims indicated above are directed to an antibody comprising CDR sequences with 100% sequence identity as shown in the following alignment files of record:
Heavy chain CDRs:
US-17-607-383-1_pep__vs__US-18-255-779A-1_pep__align.pdf
US-17-607-383-2_pep__vs__US-18-255-779A-2_pep__align.pdf
US-17-607-383-3_pep__vs__US-18-255-779A-3_pep__align.pdf
Light chain CDRs:
US-17-607-383-4_pep__vs__US-18-255-779A-4_pep__align.pdf
US-17-607-383-5_pep__vs__US-18-255-779A-5_pep__align.pdf
US-17-607-383-6_pep__vs__US-18-255-779A-6_pep__align.pdf
The sets of claims indicated above differ in scope; instant claims are directed to (a) a human monoclonal antibody type IGg1 against the hemagglutinin of an influenza A virus, (b) wherein the antibody neutralizes influenza A infection wherein the influenza virus comprises the polymorphism N146D of influenza subtype H1 NA, (c) said antibody comprises human constant heavy and light chain regions wherein heavy chain constant region comprises an M428L and a N434S mutation. Claims 1-18, 26, 31-33, 37 of copending application No. 18/255,779 include additional limitations: a) a G236A mutation, a A330L mutation, and a I332E mutation in the constant region of the heavy chain. Therefore, claims 1-18, 26, 31-33, 37 of copending application No. 18/255,779 recite a subgenus (antibody comprising a G236A mutation, a A330L mutation, and a I332E mutation in addition to an M428L and a N434S mutation) anticipate the instant genus claims (antibody comprising an M428L and a N434S mutation).
Response to Arguments
Applicant's arguments filed on 04/01/2026 have been fully considered but they are not persuasive.
Applicant contends on page 7 of the Remarks:
“A rejection under § 103 is improper when there is objective evidence establishing that the claimed invention provides unexpected results. See MPEP §§ 716.01(a) and 2145. The experimental evidence provided in the present application provides compelling evidence that the claimed antibody provides unexpected results that were not taught or suggested by Benjamin or Kuo. More specifically, the claimed antibody surprisingly provides: (i) enhanced efficacy against influenza infection that is independent from longer half-life; and (ii) decreased immunogenicity despite the presence of the MLNS substitutions.”
In response:
The instant rejection is in view of the instant claim language. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). As to applicant’s alleging unexpected results, a full explanation grounded in published evidence was provided above and previously. To reiterate, Kuo et al. teach that the introduction of an M428L and a N434S mutations in the constant region of the heavy chain results in improved binding for the neonatal Fc receptor (FcRn) as well as improved serum half-life of the antibody (page 6). The cited paragraph from the Specification (page 64, lines 24-29) clearly states that the data suggest an enhanced interaction of the claimed antibody with the hFcRn receptor, which was a known effect of the M428L and N434S mutations as taught by Kuo et al. and others such as Zalevsky et al. (Cited in applicant’s IDS submitted on 10/28/2021). Therefore, on the contrary, the effect observed and illustrated by Figures 5 and 6 in instant Specification is in fact fully expected because it was well known in the art that the M428L and N434S mutations improved receptor binding. Regardless of whether the mutations result in a change in serum half-life of the antibody or not, Kou’s teaching about improved receptor binding alone, renders the results of enhanced efficacy observed expected and obvious.
Further, with respect to Figure 5 specifically, it is noted that the survival data of the mouse model does not demonstrate unexpected results because the effects of the M428L and N434S mutations as indicated above were known in the art, therefore enhanced efficacy was in fact expected. Applicant’s remark that the differences in survival numbers were not correlated with increased half-life of the claimed antibody is unpersuasive because enhanced efficacy was expected in the light of improved receptor binding upon introduction of an M428L and an N434S mutation.
With respect to Figure 6 specifically, it is acknowledged that the pharmacokinetics of the claimed antibody illustrated in Figs. 1 and 2 show differences in antibody half-life in a 60 day period in a macaque model, and the antibody levels in mice sera shown in Figure 6 are those taken 6 days post infection in a mouse model. It is further noted that the levels of antibody in the macaque model shown in Fig. 1 do show increased half-life of the claimed antibody as compared to the parental antibody, and the difference is observable from about day 10 (Fig. 1). The mouse model data presented in Figure 6 also shows a slight increase in serum levels of the claimed antibody as compared to the parental one (see Fig. 6, day 6 in both conditions with 1 mpk and 0.3 mpk) suggesting an increase in antibody half-life. Accordingly, Applicant’s remark that the differences in survival numbers were not correlated with increased half-life of the claimed antibody is not supported by the data shown because as discussed above, both models show an increase even if it is a slight increase of antibody serum levels suggesting that the M428L and an N434S mutation does in fact confer a longer half-life to the claimed antibody. Further, as indicated above Kou also teaches improved receptor binding, which alone or in combination with the effect of increased half-life, renders the results of enhanced efficacy observed expected and obvious.
Applicant contends on page 10 of the Remarks:
“These findings were unexpected because a skilled scientist could not have predicted, based upon the cited references, that improved efficacy could be observed in a M428L/N434S modified antibody unless it was consequential to increased half-life. The interaction of FluAB_MLNS antibody with FcRn appears to trigger in vivo effects that go beyond mere half- life extension of the antibody.”
In response:
To reiterate, The instant rejection is in view of the instant claim language. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993). As to applicant’s alleging unexpected results, a full explanation grounded in published evidence was provided above and previously. To reiterate, Kuo et al. teach that the introduction of an M428L and a N434S mutations in the constant region of the heavy chain results in improved binding for the neonatal Fc receptor (FcRn) as well as improved serum half-life of the antibody (page 6). Kuo et al. provide further evidence that these effects were observed in vivo and are well known in the art. Applicant’s explanation with respect to immunogenicity and an N-glycosylation site are acknowledged. However, Applicant’s argument that the claimed antibody shows decreased immunogenicity in comparison to parental FluABwt antibody lacking the M428L/N434S mutations is neither persuasive nor surprising because the data provided in Figs. 5 and 6 and explained above in detail does not measure immunogenicity, it measures survivability and antibody levels which do not present any evidence to support immunogenicity. No T cell proliferation nor cytokine profiling nor any other data pertaining to immunogenicity was provided. Further, Applicants’ statement that improved binding for the neonatal Fc receptor (FcRn) is a key marker of immunogenicity (page 12 of the Remarks) is not supported by evidence. The refences cited of Maeda and Mackness do not teach nor suggest such conclusion. Figs. 28 and 29 in the present application presents non-specific measurements of total IgG levels at 14 days post injection in mice, which does not represent evidence of immunogenicity. Further, as noted previously the comparison of immunogenicity of a parental antibody that is identical to the claimed antibody except that it does not comprise the M428L and N434S mutations in the constant region of the heavy chain of the antibody, does not impart any additional structural features to the claimed antibody, thus such feature is considered to flow from the features already present in the antibody comprising the M428L and N434S mutations.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARLENE V BUCKMASTER whose telephone number is (703)756-5371. The examiner can normally be reached M-R 8:00 AM - 5:00 PM.
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/MARLENE V BUCKMASTER/Examiner, Art Unit 1672
NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672
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