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 .
Primary amendment
Preliminary amendment filed on 08/01/2024 has been acknowledged. Claims 1-251, 253-255, 261, 264, 266 have been canceled. Claims 252, 254, 256-260, 265 and 267-273 are pending and considered.
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 252, 257- 260, 263, 265, 267, 269 are rejected under 35 U.S.C. 103 as being unpatentable over WO2021226560A1 to Corti et al..
Claim 22 is directed to an RNA molecule and a composition as well as a method for using the same, wherein the RNA molecule can be a RNA, particularly mRNA comprising at least one coding sequence that encodes at least one SARS-CoV-2 spike protein or an immunogenic fragment or immunogenic variant thereof, wherein the SARS-CoV-2 spike protein comprises at least the amino acid substitutions P681R, K417N, T478K and D614G relative to the sequence of SEQ ID NO: 1, and wherein the RNA also comprises at least one heterologous untranslated region (UTR). Further, claim 260 cites that the RNA molecule further comprises at least the substitutions E484K and N501Y. Still further, wherein the SARS-CoV-2 spike protein further comprises an amino acid substitution at a position corresponding to L452.
In this office action, a broad reasonable interpretation (BRI) of scope of the claim 252 is not only read as a full-length spike protein of the SEQ ID NO: 1 with all claimed mutations, but also a fragment thereof, which comprise only a fragment thereof , hence, a fragment thereof may not comprise all mutations but some mutations.
The reference by Corti et al.. while it disclose a lot related to a method of making an neutralizing antibody against the envelope protein of Spike protein, the disclosure certainly teaches a spike protein mutant which is used for making an antibody, But it did specially disclose a lot SARS-CoV-2 variants or mutants that is used for immunogen to induce an antibody enhanced binding affinity to the human ACE2 receptor . One of the mutant , B.1.351 comprises spike protein or its mutant thereof, some of the mutants comprises some of the mutations cited in the current claim 252, such as K417N, E484K, N501Y, D614G, and A701 V. For example, it cites that particular, B.1.351 mutants include two other mutations in the RBD domain of SARS-CoV2 spike protein, K417N and E484K. Moreover, Coiti et al also teach that Variant L452R was also reported in California in the United States .
The reference at pages 20-21, 126, and claim 61, all disclose that the Embodiment 6.1 a SARS-CoV-2 variant such as the B.1.351 of SARS-Cov2 mutant that they use to produce or induce an neutralizing comprises any one of the following mutations in the surface glycoprotein as compared to a SARS- CoV-2 surface glycoprotein, wherein the surface glycoprotein (S) comprising one or more mutations selected from the group consisting of N501Y; S477N; N439K; L452R; E484K; K417N; T478K; S494P; A520S; N501T; A522S; Y453F; P384 of SEQ ID NO: 3.
The cited reference further teach that the term "gene" means the segment of DNA or RNA involved in producing a polypeptide chain; in certain contexts, it includes regions preceding and following the coding region ( e.g 5’ untranslated region (UTR) and 3’ UTR) as well as intervening sequences (introns) between individual coding segments (exons).
Still Further, Corti et al. also teach using the expression vector to produce such mutated polypeptide or protein For example, Cort et al. teach that “ In certain embodiments, a composition comprises a polynucleotide (e.g. mRNA) coupled to a suitable delivery vehicle or carrier. Exemplary vehicles or carriers for administration to a human subject include a lipid or lipid-derived delivery vehicle, such as a liposome, solid lipid nanoparticle, oily suspension, submicron lipid emulsion, lipid microbubble, inverse lipid micelle, cochlear liposome, lipid microtubule, lipid microcylinder, or lipid nanoparticle (LNP) or a nanoscale platform Principles, reagents, and techniques for designing appropriate mRNA and formulating mRNA-LNP and delivering the same are described in. While Coit et al. disclosed the polynucleotide such as mRNA that encodes a polypeptide of the SARS-Cov2, which is used as an immunogen for making an antibody as one embodiment of their invention, Cort et al does describe the surface antigen of the SARS-Cov2 inherently. (See pages 25-34).
The cited reference also teaches that the Embodiment 92 of the disclosed invention is drawn to . a composition comprising the polynucleotide of any one of Embodiments 73-77 encapsulated in a carrier molecule, wherein the carrier molecule optionally comprises a lipid, a lipid-derived delivery vehicle, such as a liposome, a solid lipid nanoparticle, an oily suspension, a submicron lipid emulsion, a lipid microbubble, an inverse lipid micelle, a cochlear liposome, a lipid microtubule, a lipid microcylinder, lipid nanoparticle (LNP), or a nanoscale platform,
Moreover, Cort et al. teach that it is also provided herein are methods of treating a subject using an antibody or antigen-binding fragment of the present disclosure, or a composition comprising the same, wherein the subject has, is believed to have, or is at risk for having an infection by SARS-CoV-2. "Treat," "treatment," or "ameliorate" refers to medical management of a disease, disorder, or condition of a subject (e.g, a human or non-human mammal, such as a primate, horse, cat, dog, goat, mouse, or rat). In general, an appropriate dose or treatment regimen comprising an antibody or composition of the present disclosure is administered in an amount sufficient to elicit a therapeutic or prophylactic benefit. Therapeutic or prophylactic/preventive benefit includes improved clinical outcome; lessening or alleviation of symptoms associated with a disease; decreased occurrence of symptoms; improved quality of life; longer disease-free status; diminishment of extent of disease, stabilization of disease state; delay or prevention of disease progression; remission; survival; prolonged survival; or any combination thereof. In certain embodiments, therapeutic or prophylactic/preventive benefit includes reduction or prevention of hospitalization for treatment of a SARS-CoV-2 infection (i.e., in a statistically significant manner). In certain embodiments, therapeutic or prophylactic/preventive benefit includes a reduced duration of hospitalization for treatment of a SARS-CoV-2 infection (i.e., in a statistically significant manner). In certain embodiments, therapeutic or prophylactic/preventive benefit includes a reduced or abrogated need for respiratory intervention, such as intubation and/or the use of a respirator device. In certain embodiments, therapeutic or prophylactic/preventive benefit includes reversing a late-stage disease pathology and/or reducing mortality. (See pages 36-37).
Therefore, the cited reference teach most of the structural limitations of the claims 252, 257- 260, 267, 269, 270-271 for the mutant spike protein an d method for using it to express the immunogen. used as a composition to induce an antibody production that capable of neutralizing the SARS-Cov2 virus .
Therefore, it would have been obvious for any person with an ordinary skill in the art to be motivated for using the polynucleotide or mRNA of said mutant envelope Spike protein as an immunogen to treat a patient or human being as therapeutic vaccine to induce a neutralizing antibody to neutralize the SARs-Cov2, because Cort et al. teach that “Accordingly, in certain embodiments, methods are provided for treating a SARS-CoV-2 infection in a subject, wherein the methods comprise administering to the subject an effective amount of an antibody, antigen-binding fragment, polynucleotide, vector, host cell, or composition as disclosed herein.”
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 267-268, and 270-273 are 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 making an immunogenic composition comprising the spike protein to induce an immune response to treat and /or reduce change of infection temporarily , does not reasonably provide enablement for produce a vaccine of SAR-CoV2 or to prevent a SARS-Cov2 infection. 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 and use the invention commensurate in scope with these claims.
The test of an enablement or scope of enablement is whether one skilled in the art could make and use the claimed invention from the disclosure in the application coupled with information known in the art would render undue experimentation (See United States v. Theketronic Inc., 8USPQ2d 1217 (fed Cir. 1988). Whether undue experimentation is required is not based upon a single factor but rather a conclusion reached by weighting many factors. These factors were outlined in Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and again in re Wands, 8USPQ2d 1400 (Fed. Cir. 1988), which are set forth below: 1). Nature of invention; 2). Scope of claims; 3). State of art; 4). Unpredictability; 5). Level of skill in the art; 6). Number of working examples and 7). Amount of guidance presented in the specification.
The nature of invention is directed to a RNA comprising at least one coding sequence encoding at least one SARS-CoV-2 spike protein or an immunogenic fragment or immunogenic variant thereof, wherein the SARS-CoV-2 spike protein comprises at least the amino acid substitutions P681R, K417N, T478K and D614G relative to the sequence of SEQ ID NO: 1, and wherein the RNA comprises at least one heterologous untranslated region (UTR), wherein the RNA molecule may further comprises other mutation(s) and carried or expressed by an expression vector or nanoparticle of a polymer or cationic lipid etc. that is used for inducing an antibody to treat a SARS-Cov2 infection. However, the scope of the claims under the rejection read on the RNA composition or RNA nanoparticle is a vaccine or be used to prevent any or all SARS-Cov2 infection.
It is well known in the art that SARS virus is a RNA virus that is very frequently to be mutated and get reinfected easily as evidenced by Wei et al. (Nature Communications| (2024) 15:1008, pages 1-14), who particularly reported there is a high risk of reinfection with SARS-Cov-2 Omicro variant, wherein the Omicron mutant such as B.1.1.529 comprises the same mutations L452R, K417N, E484K, and/or P681H cited in the current claims as evidenced by Gautret et al. (J. Med. Virol. 2022, Vol. 94 (8). Pp. 3494-3497). The Omicron BA.1, Omicron BA.2 and OmcronBA. 4/5 et al. all cause up to fourth infections (See Table 1 on page 3).
The specification only teaches that all spike protein comprising different mutations can induce some antibodies and cytokines.. The specification does not provide sufficient evidence and guidance to support the broad scope of the claims drawn to a vaccine to prevent any or all SARS-Cov-2 infections. Therefore, the specification fails to provide sufficient evidence to support the broad scope of claimed invention.
Given the above analysis of the factors which the courts have determined are critical in asserting whether a claimed invention is enabled, it must be considered that the skilled artisan would have to conduct undue and excessive experimentation in order to practice the claimed invention.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 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 263 is 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 that read on the L452 being modified or substituted with any or all .
The claim 26 is drawn to a genus of spike protein mutant with a mutation at L452 with any or all mutation. While it seems as if Applicants have one species of such spike mutant that are deemed capable of maintaining the same Immunogenicity and/or antibody binding capability.
MPEP § 2163.02 states, "[a] n objective standard for determining compliance with the written description requirement is “does the description clearly allow persons of ordinary skill in the art to recognize that he or she invented what is claimed’ ". The courts have decided: The purpose of the "written description" requirement is broader than to merely explain how to "make and use"; the 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 Vas-Cathy, Inc. v. Mahurkar, 935 F.2d 1555, 1563-64, 19 USPQ2d 1111, 1117 (Federal Circuit, 1991). Furthermore, the written description provision of 35 USC § 112 is severable from its enablement provision; and adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method for isolating it. See Fiers v. Revel, 25 USPQ2d 1601, 1606 (CAFC 1993) and Amgen Inc. V. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. The Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, paragraph 1, "'Written Description” Requirement (66 FR 1099-1111, January 5, 2001) states, "possession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was 'ready for patenting' such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention" (Id. at 1104).
Moreover, because the claims encompass a genus of variant species, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. However, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; nor has Applicant shown the invention was "ready for patenting" by disclosure of drawings or structural chemical formulas that show that the invention was complete; nor has Applicant described distinguishing identifying characteristics sufficient to show that Applicant were in possession of the claimed invention at the time the application was filed. In fact, Applicants only teach that substitutive mutation at position of 452 is only made from leucin (L) to Arginine ®, i.e. L452R. No any other mutant was made.
Therefore, absent a detailed and particular description of a representative number, or at least a substantial number of the members of the mRNA molecule encoding a generic polypeptide or protein , the skilled artisan could not immediately recognize or distinguish members of the claimed genus of polypeptide sequences. Moreover, since the specification has not identified which amino acid molecules of the genus of sequences, one skilled in the art would not recognize that Applicant had possession of the claimed invention at the time the application was filed. There is insufficient support the generic claims as provided by the Interim Written Description Guidelines published in the June 15, 1998 Federal Register at Volume 63, Number 114, pages 32639-32645.
The full breadth of the claims does not meet the written description provision of 35 U.S.C. 112, first paragraph.
Conclusion
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BAO Q. LI
Examiner
Art Unit 1671
/BAO Q LI/ Primary Examiner, Art Unit 1671
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