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 .
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-2, 11-12, 15-25 and 33-35) and species 180 to 1000 ug in the reply filed on 9/1/2026 is acknowledged.
Note
Claim 33, which depends from claim 26 in Group II, was inadvertently included in Group I for the Restriction Requirement dated 7/2/2026.
Status of the Claims
Claims 26-33 have been withdrawn as being directed to a non-elected invention. Claims 2, 16, 20 and 22 have been withdrawn as being directed to a non-elected species. Claims 1, 11-12, 15, 17-19, 21, 23-25 and 34-35 are under examination at this time.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informalities: Claim 1 should be amended to delete the word “An” at the beginning of the claim. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 1, 11-12, 15, 17-19, 21, 23-25 and 34-35 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claim is drawn to, inter alia, a method for prophylaxis of influenza disease in a human by administering a functional variant of instant SEQ ID NO: 6 having at least 90% identity to SEQ ID NO: 6.
The written description rejection is made because the claims are interpreted as being drawn to a method employing a genus of polypeptides recited as having “at least 90% identity to SEQ ID NO:6”. The applicable standard for the written description requirement can be found in MPEP 2163; University of California v. Eli Lilly, 43 USPQ2d 1398 at 1407; PTO Written Description Guidelines; Enzo Biochem Inc. v. Gen-Probe Inc., 63 USPQ2d 1609; Vas- Cath Inc. v. Mahurkar, 19 USPQ2d 1111; and University of Rochester v. G.D. Searle & Co., 69 USPQ2d 1886 (CAFC 2004). While one would be able to construct variants of SEQ ID NO: 6 and test them for their ability to oligomerize and function as a vaccine, this process of guesswork does not put one in possession of the genus of polypeptides used in the method. To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof. In this case, the only factor present in the disclosure is the structure of the fusion protein (i.e., SEQ ID NO:6) and the function of that structure (i.e., ability to oligomerize and function as a vaccine). There is no disclosure of any particular portion of the structure that must be conserved or that can be altered in order to have “at least 90% identity to SEQ ID NO:6” and retain the ability to oligomerize and function as a vaccine.
Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus. A definition by function alone does not suffice to sufficiently describe a coding sequence because it is only an indication of what the gene does, rather than what it is. EliLily, 119 F.3 at 1568, 43 USPQ2d at 1406.
The specification discloses at page 14 that the composition “comprises a polypeptide of SEQ ID NO:6 (OVX836) or a variant having at least 70%, 80%, preferably at least 90%, or at least 95% identity to SEQ ID NO:6.” However, the specification does not indicate which portions of SEQ ID NO:6 are essential to retain the ability to oligomerize and function as a vaccine or which portions of SEQ ID NO:6 can be modified or altered and still retain the ability to oligomerize and function as a vaccine.
The court clearly states in Vas-Cath Inc. v. Mahurkar, 19 USPQ2d 1111, that "applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the 'written description' inquiry, whatever is now claimed." (See page 1117.) The specification does not clearly allow persons of ordinary skill in the art to recognize that the inventors invented what is claimed. As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of fusion proteins that have "at least 80% identity to SEQ ID NO:6”. Given that the specification has only described the structure and function of SEQ ID NO:6, the full breadth of the claims does not meet the written description provision of 35 U.S.C. 112, first paragraph.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 1, 11-12, 15, 17-19, 21, 23-25 and 34-35 are rejected under 35 U.S.C. 103 as being unpatentable over Del Campo et al. (npj Vaccines, 2019, 4:4).
The instant claims are directed to a method for prophylaxis of influenza disease in a human subject in need thereof, said method comprising administering to said subject an immunogenic composition comprising: a fusion protein that
comprises or essentially consists of SEQ ID NO:6, or
is a functional variant of SEQ ID NO:6 having at least 90% identity to SEQ ID NO:6,
wherein said fusion protein is administered to said human subject in an amount of 180 pg, or more.
Del Campo et al. teaches that oligomeric forms of protein antigens have been shown to be more immunogenic than the monomeric forms. To enhance the immunogenicity of NP, Del Campo et al. developed OVX313, an improved version of the oligomerization domain IMX313 created as a hybrid of the C-terminal fragments of two avian C4bp α chain sequences that naturally oligomerize into heptamers. The heptameric oligomerization domain OVX313 is stabilized by intermolecular disulfide bonds, and the extremely high oligomer stability is an interesting scaffold for applications in the field of protein engineering and vaccines.
Del Campo et al. further teaches OVX836, which is a recombinant fusion protein candidate vaccine, which consists of the fusion of OVX313 with the nucleoprotein (NP) of influenza A (H1N1/WSN/1933). OVX836 increased immunogenicity over NP and protected against multiple influenza subtypes (see page 2, left column). OVX836 protected mice against viral challenge with three different influenza A subtypes, isolated several decades apart and induced a reduction in viral load (see the abstract and page 10, left column) [claims 17 and 18].
The instant specification states that instant SEQ ID NO: 6 is OVX836 (see specification page 11, lines 21-24). Therefore, Del Campo et al. teaches instant SEQ ID NO: 6.
Del Campo et al. does not teach a dose amount of 180 μg or more. However, in mice studies Del Campo et al. used doses from 6.25 μg to 50 μg. Specifically, Del Campo et al. states that the immunogenicity of the recombinant proteins NP and OVX836 were measured in C57BL6 mice following two intramuscular (i.m.) injections with doubling doses from 6.25 μg to 50 μg. Fourteen days after the last immunization, immune responses against the NP protein were detected by ex vivo IFN-γ ELISPOT to measure NP-specific IFN-γ-producing T cells in response to NP stimulation (see Figure 2e). The results showed that the NP induced moderate T-cell immune responses and OVX836 protein was more immunogenic at all doses than NP, reaching a maximum response from 25 μg (p < 0.0001). Furthermore, OVX836 elicited high titer serum NP-specific IgG antibodies, which increased with the dose and were higher than with NP at all doses (p < 0.01) (see Figure 2f) [claim 15]. Together, these results showed that the fusion protein OVX836 more effectively stimulates T cells and B cells than NP alone (see page 3).
Rhodes et al. teaches that a primary goal in vaccine development is to establish optimal vaccine efficacy, and vaccine dose amount is a crucial factor in achieving this. The consequences of selecting the wrong dose can lead to inadequate protection against disease, and ultimately wasted resources and lives. In humans, vaccine dose decisions are made based on dose escalation trials, the dose range of which is based on experiments in animals. In classical pre-clinical experiments, an initial dose is tested and incrementally increased until the dose is no longer considered safe.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to first determine the appropriate dose for humans by dose escalation trials in human subjects based on dose ranges in animal studies as taught by Rhodes et al. Del Campo et al. already teaches doses ranging from 6.25 μg to 50 μg for mice. One would have been motivated to do so and there would have been a reasonable expectation of success given the teachings of Rhodes et al. Absent unexpected results, the claimed dose range of 180 ug or more is obvious based on the teachings of Del Campo et al. and Rhodes et al.
For claim 12, it would be obvious and well within the purview of one of ordinary skill in the art to determine the number of doses (single vs more than one). According to section 2144.05 of the MPEP, “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”) Del Campo et al. teaches two doses in mice that resulted in enhanced immunity. Therefore, it is not inventive to discover other optimum or workable doses by routine experimentation. Further, applicant has not demonstrated unexpected results when the fusion protein is administered as a single dose versus more than one dose.
For claim 21, Del Campo et al. teaches the co-administration of OVX836 with inactivated influenza vaccines (IIVs) (see, for example, page 10, left column).
For claim 23, Del Campo et al. does not mention the use of an adjuvant.
For claims 24-25, the method taught by Del Campo et al. and Rhodes et al. would also produce the same results as recited in claims 24-25.
Thus, the invention as a whole was clearly prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claim is allowed.
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/NICOLE KINSEY WHITE/Primary Examiner, Art Unit 1672
