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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 November 6, 2025 has been entered.
Applicant’s amendments to the claims have overcome the rejections of record under 35 USC §§ 112(a)/(b).
In the Remarks under 35 USC §§ 102/103, applicant points out that claim 128 requires at least two hemagglutinin (HA) antigens from H1, wherein each H1 HA has at least 90% identity to SEQ ID NO: 35. Claim 128 additionally requires at least two hemagglutinin (HA) antigens from H3, wherein each H3 HA has at least 90% identity to SEQ ID NO: 53. The H1 and H3 HAs required in claim 128 are in a vaccine composition comprising six distinct HA antigens.
Applicant argues that Alexander et al. (USPgPub 2008/0032921, of record) does not provide any guidance to select six or more antigens with the claimed sequence homology, as required.
In reply, an updated search in the prior art for the recited sequences reveal known sequences in the prior art that satisfy this deficiency attributed to Alexander et al.
Applicant additionally argues that Alexander does not disclose or suggest the inclusion of multiple heterologous immunogens of the same subtype (i.e., multiple H1 hemagglutinins or multiple H3 hemagglutinins), because even though 'multivalent influenza vaccines' were referenced, the multivalency was limited to 3 strains, one per subtype (or 4, when two distinct influenza B clades emerged; still one per subtype).
Applicant’s arguments and a review of Alexander et al. have been fully considered, but are found unpersuasive. Paragraphs [0297-0302] of Alexander et al. describe a multivalent influenza virus vaccine composition. Paragraph [0299] describes “one or more polynucleotide compositions of the present invention” prime and boost the immune response. Paragraph [0058] states:
A trivalent or further multivalent composition will comprise three influenza virus polypeptides or fragments, variants or derivatives thereof, in isolated form...
Table 1, referenced in paragraph [0082] states:
Additional HA sequences of the present invention correspond to isolated wild-type HA sequences from influenza A... strains as disclosed in Table{s} 1...
These teachings satisfy the instant vaccine composition comprising (at least) six influenza type A hemagglutinin antigens recited in instant claim 128. There is no suggestion or mention in Alexander et al. limiting the multivalency “to 3 strains, one per subtype (or 4, when two distinct influenza B clades emerged; still one per subtype)”, as applicant suggests.
Applicant provides several examples of contemporaneous literature as of the instant filing date as evidence that the skilled artisan would have understood the multivalent vaccines of Alexander to refer to vaccines that have only one H1 and one H3 antigen.
Applicant’s arguments have been fully considered, but are found unpersuasive. None of the contemporaneous examples provided point to the teachings of Alexander et al. or suggest that the compositions of Alexander et al. are limited to one HA from each of two influenza virus subtypes. MPEP § 2123 discusses a prior art’s broad disclosure being relevant for all that it contains. Alexander et al. teach a multivalent influenza composition comprising multiple HA sequences in the excerpts noted above. The influenza vaccine of Alexander et al. is not limited to one HA antigen from two subtypes.
Applicant points to instant Examples 8-12, Tables 2 and 3, and Figures 7, 12, and 14, showing that the instant invention recognizes an unexpected immunogenic benefit of compiling multiple highly conserved antigens (e.g., at least two from H1 and H3), resulting in the immune response being biased towards epitopes that are shared between those immunogens, i.e., epitope focusing, that induce broader, stronger, and/or more durable cross-reactive and neutralizing immune responses than other flu vaccines described contemporaneously.
The data in the working examples and the disclosure presented has been fully considered. However, the instant claims are drawn to a vaccine composition. (“[T]he patentability of...composition claims depends on the claimed structure, not on the use or purpose of that structure.”). Catalina Mktg. Int'l, Inc. v. Coolsavings.com, Inc., 289 F.3d 801, 809 (Fed. Cir. 2002). There are no method steps required for the intended results described by applicant. In addition, the cross-reactive and neutralizing immune responses generated after administration of multiple H1 and H3 antigens is appreciated in the prior art. Carter et al. (Journal of Virology. 2009; 87: 1400-1410) show that sequential infection in ferrets with three seasonal H1 strains
confers protection against novel H1 influenza viruses, while ferrets exposed to a single H1 virus exhibited no cross-protection and limited protection after challenge, see the abstract, “Infection of ferrets”, Figures 1, 3, 4-7, and Tables 1 and 2. Huber et al. (Vaccine. 2009; 27: 1192-1200) teach administering at least 3 H3 HAs increased broad-spectrum immunity within the subtype, see the abstract, sections 3.1-3.3, and Figures 1-4. Also see page 6, line 32 to line 7, line 7; page 37, lines 23-25; lines 11-34 on page 56; and Tables 1-4, bridging pages 60-62 and 64 of Remarque et al. (WO2018/073340) demonstrating broadening the scope of protection to influenza viruses against multivalent H1 HAs and H3 HAs that are not included in the vaccine.
An updated search in the prior art based on the amended claims prompts new grounds of rejection.
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.
Claims 128, 151, 152, 154, 155, and 157 are rejected under 35 U.S.C. 103 as being unpatentable over Remarque et al. (WO2018/073340), SEQ 33 alignment with Geneseq db access no BDK47462 in WO2016201127 by Strugnell et al., SEQ 33 alignment with Geneseq db access no BEG65754 in WO2017137753 by Digard, SEQ 53 alignment with Geneseq db access no AEK61609 in WO2006098901 by Yang et al., and SEQ 53 alignment with Geneseq db access no AUY92043 in WO2008157419 by Golding et al.
On page 12, lines 31-32, Remarque et al. teach influenza hemagglutinin (HA) is approximately 560 amino acids in length.
Claims 1-3 of Remarque et al. is drawn to a vaccine composition comprising:
at least three variants of a subtype of an influenza A virus antigen, wherein,
(i) a first and second variant of a subtype of an influenza A virus antigen differ from each other by at least 10 amino acids over their entire length; and differ from each other by no more than… 55, 50, 45, 40, 35, or 30 amino acids over their entire length; (ii) a second and third variant of a subtype of an influenza A virus antigen differ from each other by at least 10 amino acids over their entire length; and differ from each other by no more than…55, or 50 amino acids over their entire length; (iii) a first and third variant of a subtype an influenza A virus antigen differ from each other by more than 35 amino acids over their entire length; and differ from each other by no more than…55, or 50 amino acids over their entire length.
Claims 4 and 5 of Remarque et al. states that the vaccine further comprises a fourth variant of a subtype of an influenza A virus antigen, wherein the fourth variant (i) differs from the third variant by at least 10 amino acids over their entire length and (ii) differs from the first variant by at least 40 amino acids over their entire length, and wherein the third and fourth variant of a subtype of an influenza A virus antigen differ from each other by no more than…55, 50, 45, 40, 35, or 30 amino acids over their entire length.
Claims 7 and 8 of Remarque et al. is drawn to the vaccine further comprises a fifth variant of a subtype of an influenza A virus antigen, wherein the fifth variant (i) differs from the fourth variant by at least 10 amino acids over their entire length and (ii) differs from the first variant by at least 50 amino acids over their entire length, and wherein the fourth and fifth variant of a subtype of an influenza A virus antigen differ from each other by no more than 55, 50, 45, 40, 35 or 30 amino acids over their entire length.
Claim 26 of Remarque et al. states that the influenza virus antigen is HA.
Claims 18, 20, 22, 24, 39, and 41 of Remarque et al. state that the influenza virus A subtype variants effect cross-neutralization against at least one influenza virus A variants that are different from those in the vaccine that comprises up to ten variants (claim 18). Also see the last three lines on page 3.
These teachings satisfy the vaccine comprising at least six distinct influenza HA antigens, where at least two HA antigens are derived from H1 and at least two HA antigens are derived from H3, as required in instant claim 128.
Line 28 on page 5 to line 21 on page 6; lines 22-36 on page 35; and lines 18-32 on page 45 of Remarque et al. lists the following influenza A H1 and H3 hemagglutinin variants included in the vaccine composition:
For H1 strains, the following HA variants were used:
A/Puerto Rico/8/1934 (SEQ ID No: 1), recited in instant claims 151 and 156;
A/USSR/92/1977;
A/Texas/36/1991;
A/New Caledonia/20/1999;, and
A/Brisbane/59/2007 (SEQ ID No: 5), recited in instant claims 152 and 156.
For H3 strains, the following HA variants were used:
A/Hong Kong/1/1968 (SEQ ID No; 9), recited in instant claims 155 and 156;
A/England/321/1977;
A/Sichuan/2/1987;
A/Nanchang/933/1995 (SEQ ID No: 12), recited in instant claims 154 and 156; or A/Johannesburg/33/94; and
A/Wyoming/3/2003 or A/Fujian/411/2002.
Although Remarque et al. do not teach or suggest an “edit distance from each of the other distinct hemagglutinin antigens that is at least 10% of an average length of the six distinct hemagglutinin antigens”, recited in instant claim 157, these parameters are inherently present in the teachings of Remarque et al. since the specific HA influenza type A antigens listed by Remarque et al. in the vaccine are reasonably equivalent or substantially equivalent under In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). The vaccine of Remarque et al. comprise two H1 HA influenza type A antigens: A/Puerto Rico/8/1934 and A/Brisbane/59/2007, recited in instant claims 151, 152, and 156 and two H3 HA influenza type A antigens: A/Hong Kong/1/1968 and A/Nanchang/933/1995, recited in instant claims 154-156. These influenza H1 and H3 HA antigens, taught by Remarque et al., necessarily possess the recited parameters and characteristics, required in instant claim 157.
Remarque et al. do not teach or suggest at least two H1 HA and at least two H3 HA antigens that share at least 90% identity to instant SEQ ID NOs: 33 and 53, respectively, recited in claim 128.
Geneseq database access no: BDK47462 in WO2016201127 by Strugnell et al. shares 100% sequence identity to SEQ ID NO: 33, see the alignment provided;
Geneseq database access no: BEG65754 in WO2017137753 by Digard shares 99.9% (rounds to 100%) sequence identity to SEQ ID NO: 33, see the alignment provided;
Geneseq database access no: AEK61609 in WO2006098901 by Yang et al. shares 99.6% (rounds to 100%) sequence identity to SEQ ID NO: 53, see the alignment provided; and
Geneseq database access no: AUY92043 in WO2008157419 by Golding et al. shares 99.4% (rounds to 99%) sequence identity to SEQ ID NO: 53, see the alignment provided.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have included the sequences of Geneseq database access no: BDK47462; Geneseq database access no: BEG65754; Geneseq database access no: AEK61609; and Geneseq database access no: AUY92043 in the vaccine composition of Remarque et al. because each of the sequences are used in influenza vaccine compositions to treat and/or prevent infection, see the description in each alignment provided. One of ordinary skill in the art prior to the instant effective filing date would have had a reasonable expectation of success to have included the sequences of Geneseq database access no: BDK47462; Geneseq database access no: BEG65754; Geneseq database access no: AEK61609; and Geneseq database access no: AUY92043 in the vaccine composition of Remarque et al. because Remarque et al. claim that up to ten subtype variants are incorporated into the vaccine, see claim 18.
Claims 147, 149, 150, and 153 are rejected under 35 U.S.C. 103 as being unpatentable over Remarque et al., Geneseq db access no BDK47462, Geneseq db access no BEG65754, Geneseq db access no AEK61609, and Geneseq db access no AUY92043, as applied to claims 128, 151, 152, 154, 155, and 157 above, and further in view of Alexander et al. (USPgPub 2008/0032921, of record).
See the teachings of Remarque et al., Geneseq db access no BDK47462, Geneseq db access no BEG65754, Geneseq db access no AEK61609, and Geneseq db access no AUY92043 above. None of the references teach or suggest the inclusion of:
A/New York/1/1918, recited in instant claims 147 and 156;
A/Denver/57, recited in instant claims 149 and 156;
A/Beijing/262/1995, recited in instant claims 150 and 156; and
A/California/07/2004, recited in instant claims 153 and 156.
Table 1, referenced in paragraph [0082] of Alexander et al. lists:
A/New York/1/1918, A/Denver/57, A/Beijing/262/1995, and A/California/07/2004, as required.
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have included an HA antigen from A/New York/1/1918, A/Denver/57, A/Beijing/262/1995, and A/California/07/2004, as taught by Alexander et al., as the HA antigens in the vaccine composition of Remarque et al., because these influenza viruses are prior pathogenic, circulating strains. One of ordinary skill in the art prior to the effective filing date would have had a reasonable expectation of success for including an HA antigen from A/New York/1/1918, A/Denver/57, A/Beijing/262/1995, and A/California/07/2004, as taught by Alexander et al., as one of the HA antigens in the vaccine composition of Remarque et al., because Remarque et al. also teach a multivalent vaccine composition comprising HA antigens from H1 and H3 classes, see line 28 on page 5 to line 21 on page 6; lines 22-36 on page 35; lines 18-32 on page 45; and claims 1-5, 7, 8, 18, 20, 22, 24, 26, 39, and 41.
Claims 148 and 156 are rejected under 35 U.S.C. 103 as being unpatentable over Remarque et al., Geneseq db access no BDK47462, Geneseq db access no BEG65754, Geneseq db access no AEK61609, Geneseq db access no AUY92043, and Alexander et al. as applied to claims 128, 147, 149-155, and 157 above, and further in view of Palese et al. (USPgPub 2018/0008696, of record).
See the teachings of Remarque et al., Geneseq db access no BDK47462, Geneseq db access no BEG65754, Geneseq db access no AEK61609, Geneseq db access no AUY92043, and Alexander et al. above.
None of the references teach A/California/07/2009, as recited in instant claims 148 and 156.
However, Palese et al. list A/California/07/2009 in paragraph [0286].
It would have been prima facie obvious to one of ordinary skill in the art prior to the instant effective filing date to have included an HA antigen from A/California/07/2009, as taught by Palese et al., as one of the HA antigens in the vaccine composition of Remarque et al., Geneseq db access no BDK47462, Geneseq db access no BEG65754, Geneseq db access no AEK61609, Geneseq db access no AUY92043, and Alexander et al., to include A/California/07/2009, as a prior pathogenic, circulating strain. One of ordinary skill in the art prior to the effective filing date would have had a reasonable expectation of success for including an HA antigen from A/California/07/2009 , as taught by Palese et al., as one of the HA antigens in the vaccine composition of Remarque et al., Geneseq db access no BDK47462, Geneseq db access no BEG65754, Geneseq db access no AEK61609, Geneseq db access no AUY92043, and Alexander et al., because Palese et al. also teach a vaccine composition comprising HA antigens from H1 and H3 classes, including A/Puerto Rico/8/1934 and A/Brisbane/59/07, as encompassed by Alexander et al. in paragraphs [0286 and 0493] and claims 1, 2, 7-10, and 35 and line 28 on page 5 to line 21 on page 6; lines 22-36 on page 35; and lines 18-32 on page 45 of Remarque et al.
Conclusion
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/Shanon A. Foley/Primary Examiner, Art Unit 1671