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 .
DETAILED ACTION
Acknowledgement is hereby made of receipt and entry of the communication filed on Jun. 30, 2026. Claims 1-2, 4, 6, 8, 10-14, 17-25, 27, 29, 31, 33-35, 37, 41-48, 50, 52, 54, 56, 58, 60, 64-65, and 67 are pending. Claims 24-25, 27, 29, 31, 33-35, 37, 41-48, 50, 52, 54, 56, 58, 60, 64-65, and 67 are withdrawn. Claims 1-2, 4, 6, 8, 10-14, and 17-23 are currently examined.
Election/Restrictions
Applicant's election without traverse of Group I (Claims 1-2, 4, 6, 8, 10-14, and 17-23), directed to a multivalent pan-influenza vaccine comprising an HA protein of an influenza virus or HA1-containing portion thereof, and/or comprising a nucleic acid encoding the HA protein or the HA1-containing portion thereof, of a different virus strain from each of any three of, or from all four of component virus strain groups H1-CVG-1 – H1-CVG-4, in the reply filed on Jun. 30, 2026, is acknowledged.
Claims 24-25, 27, 29, 31, 33-35, 37, 41-48, 50, 52, 54, 56, 58, 60, 64-65, and 67 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group.
Claim Objections
Claim 2 is objected to because of the following informalities: claim 2 recites abbreviations WS33, PR8, FM47, USSR77, BR07, SI06, NEB19 and MCH15 without spelling them out the first time they appear in the claims list. Appropriate correction is required.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-2, 4, 6, 8, 10-12, 14 and 17-18 are rejected under 35 U.S.C. 101 because the claimed invention is directed to non-statutory subject matter because it is directed to a judiciary exception.
These claims read on a combination of HA antigens from naturally occurring H1N1 strains of influenza A virus. See in the art rejection below. Each of the recited HA protein reads on a naturally occurring product. Combination of two or more components does not change the structure and properties of the components, and is not markedly different from the naturally occurring products which are a “product of nature” exception. Therefore, a claim drawn to combination of naturally occurring products is ineligible for patenting under 35 USC § 101.
Claim 12 specifies further comprising an adjuvant, and/or a pharmaceutically acceptable carrier, diluent, or excipient. Here, a pharmaceutically acceptable carrier, diluent, or excipient reads on a naturally occurring product, e.g., water.
Claim 14 recites “a component of a recombinant virus or component thereof” and “a recombinant HA or component thereof”. Here, the word “recombinant” does not specify significant difference from the naturally occurring counterpart.
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 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-2, 4, 6, 8, 10-14 and 17-23 are rejected under 35 U.S.C. 103 as being unpatentable over Darricarrère et al. (J. Virol., 2018, 92:e01349-18) in view of Marshall et al. (US 2015/0056233 A1, published on Feb. 26, 2015), Meijberg et al. (US 2014/0357845 A1, published on Dec. 4, 2014), D’Aoust et al. (US 2010/0239610 A1, published on Sep. 23, 2010) and Jasny et al. (US 2021/0162037, published on Jun. 2, 2021).
These claims are directed to a multivalent pan-influenza vaccine, comprising a haemagglutinin (HA) protein of an influenza virus or HA1-containing portion thereof, and/or comprising a nucleic acid encoding the HA protein or the HAl-containing portion thereof, of a different virus strain from each of any three of, or from all four of component virus strain groups H1-CVG1 - H1-CVG-4, wherein:
H1-CVG-1 comprises H1N1 virus strains having either (i) a HA1 Globular Head Region aa sequence having at least 91% sequence identity with SEQ ID NO: 173, and/or (ii) a conjoined Sa, Sb, Cal, Ca2, and Cb HA antigenic sites amino acid (aa) sequence having at least 82% sequence identity with SEQ ID NO:85;
H1-CVG-2 comprises H1N1 virus strains having either (i) a HA1 Globular Head Region aa sequence having at least 96% sequence identity with SEQ ID NO: 174, and/or (ii) a conjoined Sa, Sb, Cal, Ca2, and Cb HA antigenic sites aa sequence having at least 90% sequence identity with SEQ ID NO:86;
H1-CVG-3 comprises H1N1 virus strains having either (i) a HA1 Globular Head Region aa sequence having at least 93 % sequence identity with SEQ ID NO: 175, and/or (ii) a conjoined Sa, Sb, Cal, Ca2, and Cb HA antigenic sites aa sequence having at least 92% sequence identity with SEQ ID NO:87; and
H1-CVG-4 comprises H1N1 virus strains having either (i) a HA1 Globular Head Region aa sequence having at least 96% sequence identity with SEQ ID NO: 176, and/or (ii) a conjoined Sa, Sb, Cal, Ca2, and Cb HA antigenic sites aa sequence having at least 88% sequence identity with SEQ ID NO:88.
Base claim 1 encompasses an immunogenic composition comprising influenza HA antigens of H1N1 strains of three or four of four strains of influenza virus having HA sequences with i) at least 91% sequence identity to SEQ ID NO: 173, ii) at least 96% sequence identity to SEQ ID NO: 174, iii) at least 93% sequence identity to SEQ ID NO: 175, and iv) at least 96% sequence identity to SEQ ID NO: 176.
Claim 2 further specifies that the four influenza strains have: i) HA SEQ ID NO:177, and/or HA SEQ ID NO:178; ii) HA SEQ ID NO:179, and/or HA SEQ ID NO:180; iii) HA SEQ ID NO:182, and/or HA SEQ ID NO:181; and/or iv) HA SEQ ID NO:184, and/or HA SEQ ID NO:183.
Darricarrère teaches a study on development of a pan-H1 influenza virus vaccine. To determine whether combinations of specific H1 hemagglutinin (HA) antigens stimulate immune responses that protect against diverse H1 influenza viruses, the authors evaluated the antibody responses elicited by HA-ferritin nanoparticles derived from six evolutionarily divergent H1 sequences and two computationally optimized broadly reactive antigen (COBRA) HA antigens. Humoral responses were assessed against a panel of 16 representative influenza virus strains from the past 80 years. HAs from the strains A/NewCaledonia/20/1999 (NC99), A/California/04/2009 (CA09), A/HongKong/117/1977 (HK77), COBRA X6, or P1 elicited neutralization against diverse strains, and a combination of three wild-type HA or two COBRA HA nanoparticles conferred significant additional breadth beyond that observed with any individual strain. Therefore, combinations of H1 HAs may constitute a pan-H1 influenza vaccine. See Abstract.
Darricarrère teaches that H1N1 strains H1/California/07/2009 (CA09) and H1/New Caledonia/20/1999 (NC99) were selected by the WHO and remained unchanged in the vaccine composition for extended periods, 2010 to 2017 and 2000 to 2007, respectively. The other four HA candidates were selected from a time period prior to the widespread use of influenza vaccines. A/Fort Monmouth/1/1947 (FM47) was selected as a representative of a major antigenic change that resulted in the 1947 pseudopandemic. Two more candidates were chosen from a period when H3N2 largely displaced H1N1 influenza: A/Malaysia/302/1954 (MAL54) and A/Denver/1/1957 (DV57). Finally, A/Hong Kong/117/1977 (HK77) represented a candidate from the 1977 H1N1 influenza epidemic. See page 2, para 4.
Darricarrère teaches that the authors studied immunogenicity of HA-ferritin nanoparticles against a representative panel of divergent H1N1 influenza viruses. Fig. 4 shows immunogenicity of HA-ferritin nanoparticle vaccines administered to mice in bivalent (A), trivalent (B), or quadrivalent (C) combinations. See below:
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Fig 4 B and C show combinations of H1N1 HA antigens from three different H1N1 strains (Fig. 4B) or four different H1N1 strains (Fig. 4C), from selected H1N1 strains of NC99, CA09, FM47, Mal54, and HK77.
Darricarrère teaches that the HA ectodomain from various H1N1 strains was genetically fused to the N terminus of Helicobacter pyloribullfrog hybrid ferritin. HA sequences from the following influenza virus strains were used to construct the HA-nanoparticles: A/Fort Monmouth/1-JY2/1947 (GenBank accession no. CY147342, amino acids 1 to 518, Y108F), A/Malaysia/302/1954 (accession no. CY009340.1, amino acids 1 to 518, Y108F), A/Denver/1/1957 (accession no. CY008988, amino acids 1 to 517, Y108F), A/Hong Kong/117/1977 (accession no. CY009292, amino acids 1 to 518, Y108F), A/New Caledonia/20/99 (accession no. AHJ09883.1, amino acids 1 to 518), A/California/4/2009 (accession no. AHJ09884.1, amino acids 1 to 518), COBRA P1 (Seq Id 2; amino acids 1 to 518, Y108F), and COBRA X6 (amino acids 1 to 517, Y108F). The HA-ferritin genes were cloned into the XbaI/BamHI sites of SIB002 vector for mammalian expression, with a GCCACC Kozak sequence in front of the ATG start codon. See page 11, para 4. Here, the HA ectodomain comprises the HA1 portion and the stem region of the HA protein.
Accordingly, Darricarrère teaches a multivalent pan-influenza vaccine comprising three (trivalent) or four (quadrivalent) HA ectodomain antigens from three or four evolutionarily/antigenically distinct H1N1 strains, selected from: 1) FM47 (A/Fort Monmouth/1-JY2/1947, GenBank accession no. CY147342), 2) Mal54 (A/Malaysia/302/1954 (accession no. CY009340)), 3) HK77 (A/Hong Kong/117/1977 (accession no. CY009292)), 4) NC99 (A/New Caledonia/20/99 (accession no. AHJ09883.1)), and 5) CA09 (A/California/4/2009 (accession no. AHJ09884.1)).
The identity of the above HA sequences to SEQ ID NOs: 173-176 recited in claim 1, calculated based on amino acid sequences associated with the Genbank accession numbers, is shown in the table below:
FM47
Mal54
Hk77
NC99
CA09
SEQ 173
86.5%
84.92%
84.92%
80.95%
73.81%
SEQ 174
96.83%
93.65%
93.65%
86.11%
69.84%
SEQ 175
85.71%
84.52%
84.52%
96.03%
68.25%
SEQ 176
68.25%
67.86%
67.86%
65.87%
95.24%
However, only two of the above five H1N1 strains, FM47 comprising a sequence 96.83% identical to SEQ ID NO: 174 and NC99 comprising a sequence 96.03% identical to SEQ ID NO: 175, satisfy the sequence requirement of claim 1.
Marshall et al. (US 2015/0056233 A1, published on Feb. 26, 2015), Meijberg et al. (US 2014/0357845 A1, published on Dec. 4, 2014), D’Aoust et al. (US 2010/0239610 A1, published on Sep. 23, 2010) and Jasny et al. (US 2021/0162037, published on Jun. 2, 2021) each individually teaches influenza vaccine compositions involving influenza virus HA antigens.
Marshall discloses an HA sequence, SEQ ID NO: 113, that is identical to the instant SEQ ID NO: 177.
Meijberg discloses an HA sequence, SEQ ID NO: 69, that is identical to the instant SEQ ID NO: 180. Meijberg teaches that SEQ ID NO: 69 represents the HA sequence of A/USSR/90/1977(H1N1). See Table 7.
D’Aoust discloses an HA sequence, SEQ ID NO: 49, that is identical to the instant SEQ ID NO: 181. D’Aoust teaches that FIG. 40B shows the amino acid sequence (SEQ ID NO: 49) of the polypeptide translated from clone 775 (A/Solomon Islands 3/2006 (H1N1)). See [0091].
Jasny discloses HA sequences, SEQ ID NOs: 779 and 13686, that are identical to the instant SEQ ID NOs: 179 and 183, respectively.
Accordingly, teachings of Marshall, Meijberg, D’Aoust and Jasny indicate that influenza H1N1 HA antigens comprising one of the sequences 177, 179-181 and 183, specified in claim 2, are known in the art at the time of invention. These sequences are species encompassed by the generic sequences specified in claim 1.
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the current invention to introduce the H1N1 HA antigens disclosed Marshall, Meijberg, D’Aoust and Jasny, including those with the sequences specified in the instant claim 2, into the study of Darricarrère to evaluate the immunogenic effect of those HA antigens in a pan-H1 influenza vaccine. Additionally, such a combination, or a substitution of one element for another known in the field to have the same function, is evidence that the claimed invention may be found obvious. See MPEP 2144.06 and KSR International v. Teleflex Inc., 82 U.S.P.Q.2d 1385, at 1395. Therefore, the instant 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.
Regarding claims 2 and 4, since Marshall, Meijberg, D’Aoust and Jasny disclose the HA antigens comprising the same amino acid sequence of the claimed strains, they are considered to be originated from the claimed strains (as only the HA antigens are required in the claimed composition).
Regarding claims 6 and 8, none of Darricarrère, Marshall, Meijberg, D’Aoust and Jasny teach that the HA sequences have been mutated, including mutated in the predicted and/or confirmed NLG glycosylation sites. One of skill in the art would have found it obvious not to do so in order to keep the original immunogenic activities of the wild-type HA antigens in the study.
Regarding claims 12-13, Darricarrère teaches that SAS and AF03 adjuvants can be used in the formulation of vaccines (see Fig. 3 legend), and Meijiberg teaches that suitable adjuvants can include aluminum salts such as aluminum hydroxide and/or aluminum phosphate, oil-emulsion compositions (or oil-in-water compositions), including squalene-water emulsions, such as MF59 etc. (see [0202]).
Regarding claims 14 and 17, Darricarrère teaches that the HA antigens of different H1 strains are incorporated in nanoparticles. See discussions above. D’Aout teaches that influenza virus vaccines may include inactivated viral vaccines and live attenuated vaccines. See [0006].
Regarding claim 18, since Darricarrère, Marshall, Meijberg, D’Aoust and Jasny disclose the HA antigens specified in all of the claimed groups, it would have been well within the purview of one of skill in the art to select the number of different HA antigens from each group to include in a pan-H1 vaccine composition, including one from each group, as claimed.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NIANXIANG (NICK) ZOU whose telephone number is (571)272-2850. The examiner can normally be reached on Monday - Friday, 8:30 am - 5:00 pm, EST. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, MICHAEL ALLEN, on (571) 270-3497, can be reached. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NIANXIANG ZOU/
Primary Examiner, Art Unit 1671
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