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
Priority
This Application is a national phase application filed under 35 U.S.C. § 371 claiming priority to International Application No. PCT/CA2021/050554, filed on April 22, 2021, which claims priority to U.S. Application No. 63/014,008, filed on April 22, 2020, that is hereby acknowledged by the Examiner.
Status of the Claims
The amendment dated 10/21/2022 is acknowledged. Claims 1-3, 6, 8, 11, 13-15, 20, 22-24, 27-28, 33-34 and 36-38 are pending and under examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/08/2024 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement(s) is/are being considered by the Examiner.
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.
Claims 8, 24, 27-28, 34 and 36-38 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 8 recites “preferably”. The term "preferably" in claim 8 is a relative term which renders the claim indefinite. The term "preferably" is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Thus, the claim is rendered indefinite.
Claims 36-37 recite “suprastructure”. The claim is unclear in that the Applicant’s disclosure does not explicitly define the term “suprastructure”. The disclosure merely gives exemplary statements for a suprastructure and state the suprastructure may be a VLP (paragraph [0006]), then states a composition comprising “the suprastructure or VLP” (paragraph [0020]). The term “suprastructure” is not defined explicitly and distinctly, particularly in view of the fact that influenza hemagglutinin is a trimer. The inclusion of said term renders the scope of these claims indefinite.
Claims 24, 27-28, 34 and 38 are directed to a method of inducing immunity to influenza virus infection; method of administering a vaccine of claim 11 to a subject; and a method of producing a VLP, whereby the vaccine of claim 11 comprises the composition of claim 8 that is a VLP of claim 1 comprising modified HAs; however, the claims are not clear and concise in that the modified HAs are not adequately defined by structure, i.e., amino acid sequence. A skilled artisan would not be apprised of the metes and bounds of claimed compositions for use in claimed method(s). Therefore, the claims are rendered indefinite.
The following is a quotation 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.
Claims 1, 6, 8, 11, 13-14, 20, 22-24, 27-28, 33-34, 36-38 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are directed to a virus-like particle (VLP) comprising modified influenza hemagglutinin (HA), the modified HA comprising one or more than one alteration that reduces non-cognate interaction of the modified HA to sialic acid (SA) of a protein on the surface of a cell, while maintaining cognate interaction with the cell, optionally wherein the cell is a B cell, optionally wherein the protein on the surface of the cell is a B cell surface receptor.
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.
The grounds for the written description rejection are as follows: (1) the claims read on a modified influenza hemagglutinin (HA) comprising one or more than one alteration that reduces non-cognate interaction of the modified HA to sialic acid (SA) of a protein, without specifying how the HA is modified to achieve the claimed function.
It is understood by the Office that the instant claims encompass a genus of HA polypeptides having alterations of any portion of the modified HA and only indicates that there is a reduction in in non-cognate interaction to sialic acid of a protein. One skilled in the art would not be able to envision all alterations of the polypeptides for the claimed function. While it is possible to make polypeptides having a mutation (e.g. insertion, deletion, substitution) and test them for the claimed function, the specification must provide an adequate description of the genus. There is nothing in the claims that limit the modification of the HA protein to a specific sequence in the polypeptide that allows a skilled artisan to ascertain how to make the construct for encoding the modified HA protein while maintaining the functional limitation. There is some general teaching in the art that some amino acid variations are tolerated without losing a protein' s tertiary structure, but conservation of structure is not necessarily a surrogate for conservation of function. The provision of a partial structure and a function without a nexus between the two does not put one in possession of the large genus of variants encompassed by the claim. Vas-Cath Inc. V. Mahurkar, 19 USPQ2d 1111, clearly states 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 [he or she] invented what is claimed." (See Vas-Cath at page 1116).
The claims do not provide an adequate description of how the constructs are made to produce a modified Influenza HA polypeptide with the claimed function. Thus, the Applicant has not shown, otherwise, which modifications to the HA polypeptide would reduce non-cognate interaction to sialic acid and retain cognate interaction with the cell. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the Applicant has not provided adequate written description to support the claimed genus of the construct limited by the function of the HA polypeptide.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 14-15, 22 and 33-34 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Nabel et al. “Nabel” (WO2019/195284, IDS of record dated 11/08/2024).
The claims are directed to (1) a virus like particle (VLP) comprising modified influenza hemagglutinin (HA), the modified HA comprising one or more than one alteration that reduces non-cognate interaction of the modified HA to sialic acid (SA) of a protein on the surface of a cell, while maintaining cognate interaction with the cell, optionally wherein the cell is a B cell, optionally wherein the protein on the surface of the cell is a B cell surface receptor; and (2) The VLP of claim 1, wherein, the modified HA is being selected from: i) a modified H1 HA, wherein the one or more than one alteration is Y91F; wherein the numbering of the alteration corresponds to the position of reference sequence with SEQ ID NO: 203: ii) a modified H3 HA, wherein the one or more than one alteration is selected from Y98F, S136D; Y98F, S136N; Y98F, S137N; Y98F, D190G; Y98F, D190K; Y98F, R222W; Y98F, S228N; Y98F, S228Q; S136D; S136N; D190K; S228N; and S228Q; wherein the numbering of the alteration corresponds to position of reference sequence with SEQ ID NO: 204; iii) a modified HS HA, wherein the one or more than one alteration is Y91F; wherein the numbering of the alteration corresponds to position of reference sequence with SEQ ID NO: 205; iv) a modified H7 HA, wherein the one or more than one alteration is Y88F; wherein the numbering of the alteration corresponds to position of reference sequence with SEQ ID NO: 206; v) a modified B HA, wherein the one or more than one alteration is selected from S140A; S142A; G138A; L203A; D195G; and L203W; wherein the numbering of the alteration corresponds to position of reference sequence with SEQ ID NO: 207; or
vi) a combination thereof.
Regarding claims 14-15, 22 and 33-34, Nabel discloses vaccines comprising an influenza A (Abstract) hemagglutinin H1 in which the amino acid corresponding to position 91 of instant SEQ ID NO: 203 is phenylalanine (Y91F) (SEQ ID NO: 15 of Nabel). Nabel also discloses an influenza A hemagglutinin H5 in which the amino acid corresponding to position 91 of instant SEQ ID NO: 205 is phenylalanine (Y91F) (SEQ ID NO: 20 of Nabel). With respect to the functional limitation that the modified HA reduces non-cognate interaction to sialic acid while maintaining cognate interaction with the cell, the defined structures (i.e. amino acid substitutions) of the claimed modified HA is the same as the cited prior art of Nabel et al, thus, would have the same function. The MPEP states that “the express, implicit, and inherent disclosures of a prior art reference may be relied upon in the rejection of claims under 35 U.S.C. 102 or 103. "The inherent teaching of a prior art reference, a question of fact, arises both in the context of anticipation and obviousness." In re Napier, 55 F.3d 610, 613, 34 USPQ2d 1782, 1784 (Fed. Cir. 1995) (affirmed a 35 U.S.C. 103 rejection based in part on inherent disclosure in one of the references). See also In re Grasselli, 713 F.2d 731, 739, 218 USPQ 769, 775 (Fed. Cir. 1983)” (see MPEP 2112). section 2112(II) of the MPEP states that there is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference. Schering Corp. v. Geneva Pharm. Inc., 339 F.3d 1373, 1377, 67 USPQ2d 1664, 1668 (Fed. Cir. 2003) (rejecting the contention that inherent anticipation requires recognition by a person of ordinary skill in the art before the critical date and allowing expert testimony with respect to post-critical date clinical trials to show inherency); see also Toro Co. v. Deere & Co., 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004)(“[T]he fact that a characteristic is a necessary feature or result of a prior-art embodiment (that is itself sufficiently described and enabled) is enough for inherent anticipation, even if that fact was unknown at the time of the prior invention.”); Atlas Powder Co. v. Ireco, Inc., 190 F.3d 1342, 1348-49 (Fed. Cir. 1999) (“Because sufficient aeration' was inherent in the prior art, it is irrelevant that the prior art did not recognize the key aspect of [the] invention.... An inherent structure, composition, or function is not necessarily known.”). Therefore, the cited prior art anticipates the claimed invention.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
Claims 1-3, 6, 8, 11, 20, 23, 27-28 and 38 are rejected under 35 U.S.C. 103(a) as being unpatentable over Nabel et al. “Nabel” (WO2019/195284, IDS of record dated 11/08/2024) as applied to claims 14-15, 22, 33-34 above, in view of Graham et al. “Graham” (CA 2974346, IDS of record dated 11/08/2024). The teachings of Nabel et al. are outlined above and incorporated herein.
The claims are directed to a virus like particle (VLP) comprising modified influenza hemagglutinin (HA), the modified HA comprising one or more than one alteration that reduces non-cognate interaction of the modified HA to sialic acid (SA) of a protein on the surface of a cell, while maintaining cognate interaction with the cell, optionally wherein the cell is a B cell, optionally wherein the protein on the surface of the cell is a B cell surface receptor.
Regarding claims 1-3, 6, 8, 11, 20, 23, 27, 28 and 38, Nabel discloses vaccines comprising a modified HA comprising Y91F as the instant claims) (SEQ ID NO: 15 of Nabel).
Although Nabel teaches cross-reactivity of nanoparticles are consistent with their counterpart VLPs, Nabel does not explicitly teach a VLP comprising the modified HA.
Graham, however, discloses VLPs comprising modified HAs of influenza A H1. Graham discloses H1 in which the amino acid at position 98 is mutated to phenylalanine to reduce sialic acid binding (page 67 lines 2-5, Table 1) (instant claims 1-3 and 8). Graham discloses the use of VLPs and nanoparticles as influenza vaccines (page 9 last para and page 47 second para.) (instant claims 6, 11, 20, 27 and 38). Graham discloses the modified HAs can be produced from nucleic acid molecules (page 17 last para.) (instant claim 28); and embodiments whereby the self-assembling subunit proteins of the nanoparticles can be derived from plants (page 44 second para.) (instant claim 23). Graham states “Instead of embryonated eggs, VLPs comprising HA, NA and matrix protein 1 (M1) can be mass-produced in mammalian or insect cell expression systems. The advantages of this approach are its particulate, multivalent nature and the authentic display of properly folded HA proteins that faithfully mimic the infectious virion” (page 9 last para.).
Accordingly, it would have been obvious to one of ordinary skill in the art to generate modified HAs comprising a Y91F substitution to reduce non-cognate interaction to sialic acid as disclosed by Nabel, whereby the modified HAs are made into virus-like particles comprising modified HAs to sialic acid to reduce binding as disclosed by Graham. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success given the knowledge that the Nabel and Graham demonstrate modified HAs to reduce interactions to sialic acid and that Graham teaches the advantage of VLPs to overcome the limitations of manufacturing, time consuming process, and highly strain-specific efficacy and its particulate, multivalent nature and the authentic display of properly folded HA proteins that faithfully mimic the infectious virion (page 9 last para.). Therefore, the claimed invention would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Barry Chestnut whose telephone number is (571)270-3546. The examiner can normally be reached on M-Th 8:00 to 4:00.
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.
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/BARRY A CHESTNUT/Primary Examiner, Art Unit 1672