DETAILED ACTION
Election/Restrictions
Applicant's election with traverse of selected species in the reply filed on June 30, 2026 is acknowledged. The elected species are: protein, monovalent and SEQ ID NO: 15. The traversal with regard to the amino acid sequences is on the ground(s) that SEQ ID NO: 1 and 15 refer to the same influenza antigen in full-length and soluble form. This is found persuasive, thus SEQ ID NO: 1 and 15 will be examined together as a single species of HA antigen, Y2.
Regarding the rest of the species election which was not traversed, the requirement is still deemed proper and is therefore made FINAL.
Claims Summary
Claims 1-3, 5-9, 12 and 13
Claim 1 is directed to a non-naturally occurring, recombinant, and immunogenic influenza virus antigen comprising or consisting of an amino acid sequence that is at least 98% identical to an amino acid sequence of a HA protein antigen of SEQ ID NO: 1 or 15, or an immunogenic portion thereof. SEQ ID NO: 15 is 579-aa and represents a soluble HA protein of Y2. SEQ ID NO: 1 is 551-aa and represents the full-length HA protein of Y2. The influenza virus is an H1 or H3 influenza virus (claim 2). Also claimed is a VLP comprising the antigen (claim 3), an immunogenic composition or vaccine comprising the antigen or a VLP (claim 6). Claim 5 is directed to an embodiment wherein the antigen is characterized as generating an immune response comprising the production of neutralizing antibodies. Claim 7 is directed to a method of treating, protecting, and/or generating an immune response in a subject by administering the virus antigen, VLP or immunogen. The subject is infected with influenza virus, or is at risk of or susceptible to infection by influenza virus (claim 8). The subject generates an immune response comprising the production of neutralizing antibodies, a cellular immune response, and/or the production of T-lymphocytes (claim 9). Also claimed is a monovalent immunogen comprising the virus antigen (claim 12), comprising the Y2 antigen comprising SEQ ID NO: 15 (claim 13).
Claim 4
Claim is directed to a non-naturally occurring, recombinant immunogen comprising an amino acid sequence that is at least 98% identical to an amino acid sequence of a HA protein antigen as set forth in SEQ ID NO: 1 or 15. The immunogen is capable of generating an immune response against present and future influenza virus strains.
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, 5 and 12 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a law of nature without significantly more. The claims recite an immunogenic portion of an influenza virus hemagglutinin antigen (HA) of SEQ ID NO: 1 or 15. While the HA antigen comprising SEQ ID NO: 1 or 15 does not appear to be a product of nature, an immunogenic portion is a product of nature exception. The characteristics of an immunogenic portion of the HA antigen comprising SEQ ID NO: 1 or 15 are not markedly different from the product’s naturally occurring counterpart in its natural state because it conveys the same amino acid information. Bakri et al. (PLoS ONE, 2019, 14(3):E0213290, 15 pages) discloses a Palestinian A(H1N1)pdm09 isolate of influenza virus having a sequence represented by GenBank accession number KY075821 (see page 3, first full paragraph, last sentence, and page 6, first full paragraph, last sentence). Bakri’s sequence is 94% identical to Applicant’s SEQ ID NO: 15. Immunogenic portions of Applicant’s sequence that are 98%-100% identical to Bakri’s sequence are not markedly different from the naturally occurring counterpart represented by Bakri’s sequence. An alignment is provided toward the end of this document.
Although the claims state that the antigen is non-naturally occurring and recombinant, the fact is that the amino acid information for an immunogenic fragment is the same as that of its naturally occurring counterpart. Thus the descriptors, “non-naturally occurring” and “recombinant” do not impart any structural difference to the antigen compared to its naturally occurring counterpart. The limitations in claim 3 about the virus being an H1 or H3 influenza virus do not impart any structural difference to the sequence itself. The limitations in claim 5 about the antigen generating an immune response comprising neutralizing antibodies are expected to an inherent feature of the antigen, and the same is expected of the naturally occurring counterpart. The limitations in claim 12 about the immunogen being monovalent does not change the structure of the antigen.
This judicial exception is not integrated into a practical application. The limitations in product claim 5 about the antigen generating an immune response comprising neutralizing antibodies are not paired with any other components in the claim besides the antigen itself.
The claims do not include additional elements that are sufficient to amount to significantly more than the judicial exception because the claims do not include any additional elements.
Therefore, the claims are directed to a judicial exception and are not patent eligible. Removing the embodiment directed to the immunogenic portion would overcome this rejection.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 4, 6 and 7 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 4 is directed to an embodiment wherein the immunogen is capable of generating an immune response against present and future influenza virus strains. “Present” influenza virus strains is not clear because the strains that qualify as “present” are subjective. “Future” influenza virus strains are not known. Thus, the metes and bounds of the terms cannot be determined.
Claim 6 recites the limitation “the immunogen of claim 1 or a virus-like particle comprising the immunogen of claim 1”. Claim 1 is directed to an antigen, not an immunogen.
Claim 7 recites the limitation “virus antigen, VLP or immunogen of claim 6". There is insufficient antecedent basis for this limitation in the claim.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 4 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for an immunogen that generates an immune response against influenza virus, does not reasonably provide enablement for an immunogen that generates an immune response against a future influenza virus strain. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make or use the invention commensurate in scope with these claims.
The breadth of the claim encompasses an influenza HA immunogen comprising SEQ ID NO: 1 or 15. The specification characterizes SEQ ID NO: 1 and 15, representing full-length and soluble forms of antigen Y2, as broadly reactive (see paragraph [0025]). The immunogen is capable of inducing an immune response against future influenza strains. Future influenza strains are those that do not yet exist.
The nature of the invention is an influenza HA immunogen that, when administered to a subject, will induce an immune response against future strains of influenza.
It would be impossible for the specification to disclose future strains of influenza, thus one would not be able to predict whether an immunogen comprising SEQ ID NO: 1 or 15
Therefore, in view of the breadth of the claim, the nature of the invention, the teachings of the specification, the lack of working examples, and lack of predictability, it would require undue experimentation to make and use the claimed immunogen for the purpose of inducing an immune response against future strains of influenza.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1, 2, 5-9 and 12 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Sodoyer et al. (US Patent 10,118,951, “Sodoyer”). The claims are summarized and correlated with the teachings of the prior art in bold font below.
Claim 1 is directed to a non-naturally occurring, recombinant and immunogenic influenza virus antigen comprising an immunogenic portion of an amino acid sequence that is at least 98% identical to SEQ ID NO: 1 or 15. Thus, a sequence that comprises an identical immunogenic portion of SEQ ID NO: 1 or 15 meets the sequence limitations of claim 1.
Sodoyer discloses HA or fragments thereof from subtypes H1 and H3, among others, that have been codon optimized (thus recombinant and not naturally occurring) (see col. 10, lines 25-35, and Example 3, col. 22, lines 36-63) (claims 1 and 2). Sodoyer discloses a sequence (SEQ ID NO: 28) of an influenza HA that is 93.3% identical to Applicant’s SEQ ID NO: 15. Given that there are regions of 100% identity with Sodoyer’s sequence (alignment provided toward the end of this document), Sodoyer’s sequence meets the sequence limitations of claim 1. Fragments of Sodoyer’s HA sequence are the ectodomain (see col. 10, lines 51-58). Since the sequence is the HA sequence, used for vaccines, fragments are expected to be immunogenic. As for inducing neutralizing antibodies, cellular immunity and/or the production of T-lymphocytes, since the structural limitations of claim 1 are met, any properties of the antigen are inherent (claims 5 and 9). Sodoyer discloses immunogenic compositions and vaccines for administration to induce an immune response against influenza in subjects (see col. 16, lines 52-60 and col. 17, lines 27-40) (claims 6 and 7). A vaccine implies that the recipient is at risk of or susceptible to influenza virus infection (claim 8). Sodoyer’s compositions comprise multimerized recombinant proteins, but are monovalent in the sense that only one antigen is being multimerized (see col. 15, lines 56-60) (claim 12). Therefore, the claimed embodiments are anticipated by the prior art.
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.
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.
Claim 3 is rejected under 35 U.S.C. 103 as being unpatentable over Ross et al. (US 2014/0127248) in view of Sodoyer et al. (US Patent 10,118,951, “Sodoyer”) and Kang et al. (Virus Research, 2009, 143:141-146, “Kang”). Claim 3 is directed to a VLP comprising the antigen of claim 1.
Kang discloses influenza VLPs comprising HA, noting advantages of the VLP platform as safe, able to activate APCs, resemble intact virions, viral glycoproteins in native conformation, etc. (see pages 141-142, bridging paragraph). Kang does not disclose the antigen as claimed in claim 1, however, the teachings of Sodoyer are outlined above as they pertain to the influenza antigen itself. One would have been motivated to make VLPs with any influenza HA antigen given the advantages named by Kang, with a reasonable expectation of success, further in view of Ross’ disclosure of influenza H1N1 antigens in various immunogenic formats, such as polypeptides, fusion proteins and VLPs (see abstract). Therefore, the claimed subject matter would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Sequence Alignment of Bakri’s A(H1N1)pdm09 isolate (“Db”) with Applicant’s SEQ ID NO: 15 (“Qy”)
PNG
media_image1.png
744
564
media_image1.png
Greyscale
Sequence Alignment of Sodoyer’s SEQ ID NO: 28 (“Db”) with Applicant’s SEQ ID NO: 15 (“Qy”)
PNG
media_image2.png
826
564
media_image2.png
Greyscale
Conclusion
No claim is allowed. Claim 13 is objected to for being dependent on a rejected claim but would otherwise be allowable if rewritten in independent form and limited to the elected species.
A sequence that is at least 98% identical to SEQ ID NO: 1 or at least 98% identical to SEQ ID NO: 15 is free of the prior art of record.
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Stacy B. Chen whose telephone number is 571-272-0896. The examiner can normally be reached on M-F (7:00-4:30). If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Thomas Visone, can be reached on 571-270-0684. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
/STACY B CHEN/Primary Examiner, Art Unit 1672
Prosecution Insights