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 .
Summary
Applicant’s response and amendment were filed on 11/19/2025/
Claims 1-21 , 26 and 28 were amended.
Claim 27 was canceled.
Claims 1-16 and 28 are were considered.
Claims 1-16 and 27-28 with the scope of SEQ ID NO: 10 are considered. Claims 17-26 are withdrawn from consideration.
Claim Objections
The objection of Claims 2, 6 and 8 are removed because the persuasive argument.
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.
The rejection of Claims 6 and 16 is removed because the persuasive argument.
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.
Claim(s)1-5, 8-10 and 16 are still rejected under 35 U.S.C. 103 as being unpatentable over WO 2008005777 A2 to Novax Inc. (Hereinafter Novax) in view of US 20170233762 to the regents of University of California (hereinafter California), US Patent NO: 5,378,821 to Harman et al. US 7,145,060B2 to Muller et al. and Tipper et al. (Journal of Immunology Research, 26 April 2016, pages 1-15).
In the response, Applicants submit that the claim 1 has been amended , such that the claimed recombinant yeast cell is comprised in a vaccine composition which comprises a pharmaceutical acceptable excipient or foodstuff, as well as matrix protein.
Applicants’ argument has been respectfully considered; however, it is not found persuasive for the following reasons:
(i). The cited vaccine composition is considered as preamble language. The claimed limitations are considered based on the components or the structural characteristics in the composition.
(ii) The amendment of added limitations of pharmaceutical acceptable carrier or food stuff is only considered as one of the choices in the composition rather than as a limitation absolutely required by the claim.
(iii). The cited viral matrix protein or functional fragment thereof, viral capsid protein or functional fragment thereof, or viral structural protein or functional fragment thereof, is an one of choice in the composition rather than as a limitation absolutely required by the claim.
To this context, the rejection is maintained as the clamed subject matter cited in the rejected claims are still considered to be an obvious to the cited prior arts in combination.
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, 10, 16 are still rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Aizi Nor Mazila Rammli et al. (Micro. Cell Fact. 2011m Nov. 4: 10: 94, doi: 10,1186/1475-2859-10-94).
Applicants traverse the rejection and asserted Office action fails to explain why any one of the references anticipates, i.e., none of the references discloses or even mentions a vaccine, let alone a vaccine comprising a recombinant yeast cell as recited in claim 1. Thus, claims 1, 10, and 16 are patentable over the references. Withdrawal of the rejections is respectfully requested.
Applicants’ argument has been respectfully considered; however, it is not persuasive because the argument is not factual. Because in the beginning of the conclusion of the previous cited reference, the conclusion is now stated herein :
“Results: A gene encoding a cold-adapted chitinase (CHI II) from Glaciozyma antarctica PI12 was isolated using Rapid Amplification of cDNA Ends (RACE) and RT-PCR techniques. The isolated gene was successfully expressed in the Pichia pastoris expression system.”
In the previous office action, the office action describes that Ramli et al. teach a recombinant yeast cell, i.e. psychrophilic yeast comprising a nuclei acid sequence encoding a recombinant chitinase (CHI II) of G . Antarctica P112, wherein the expression of CHII was conducted in P. pastoris expression system (See Fig. 1).
Regarding the limitaiton of claims 10 and 16 which only are cited with inherently property of the Chitinase rather any other added structural property additionally added to the claimed recombinant chitinase.
Therefore, the rejection is maintained.
Claim(s) 1, 11-12 and 16 are rejected under 35 U.S.C. 102 (a) (1) as being anticipated by Schreuder et al. (Vaccine, published in April 1996, Vol. 14, issue 5, pp. 383-388).
Schreuder et al. teach an oral e made by a recombinant yeast that is genetically engineered to express hepatitis B virus surface antigen determinants on its surface: and implications it for a possible oral vaccine. In particular, they harvested the recombinant Yest cells that expressing theses antigenic epitopes, washed the harvested recombinant Yeast and prepared then in 0.9% NaCl and heat-killed the yeasted cells and later fed the mice with the heat inactivated recombinant Yeast cells as a vaccine . The boost immunization was done in a period of 4 weeks. (See Martials and Methods, particular the section of Immunization of mice with Yeast cells expressing HBs3 protein.
A specific immunological response against HBS surface antigen HBsAg were observed after the immunization. They concluded that Yeast Saccharomyces in an excellent eukaryotic expression system, which can be used as a vaccine carrier because it is cheaply producible and is also safe in oral use. It seems to be a good candidate for the development of a live oral vaccine (See page 387)
It is worth to note that the 0.9$ NaCl is a considered as stuff as it is a physically accepted concentration of NaCl that can be used as a drinkable solution in daily life and clinical too. Moreover, HBsAg is presented as a virus like particles (Fig. 4) . Because this particle is made from HBsAg envelope only without virus genetic DNA , it can be considered as a virus like particle (VLP).
Still further, regarding the Beta-glucan, and 𝛽-(1,3)-D-glucan, it is worth to note Beta-glucan, primarily derived from Saccharomyces cerevisiae cell walls, which is a natural polysaccharide composed of 𝛽-(1,3)-D-glucan chains with β -(1,6) branches, making up 30-60% of the cell wall dry weight, it provides structural integrity and acts as a major immune-modulating, health-boosting compound as evidenced by Liu et al. (Int. Biol Macromol. 2021, Mar. 15: 173: 445-456). Therefore, the cited reference anticipates claims 1, 2-3, 8, 9, 10, 11, 12 and 28.
Claim Rejections - 35 USC § 112
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 1-16 and 27-28 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 producing a recombinant virus matrix protein by a recombinant yeast cell and using it as an immunogenic composition comprising a virus like particle made by influenza HA envelop protein and HIV gag protein , wherein both of them are expressed by a recombinant yeast cell, does not reasonably provide enablement for having a vaccine made by a recombinant yeast cell to express any or all viral matrix protein. 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; 6). Number of working examples and 7). Amount of guidance presented in the specification.
The nature of invention is directed to a method for expressing a recombinant viral matrix or capsid protein such as influenza virus M protein by a recombinant yeast cell and prepare it as an immunogenic composition capable of being delivered orally, herein to induce an immune response in a subject.
However, the scope of the claims are directed to a vaccine composition by the claimed recombinant yeast cells carrying any or all heterologous antigen operably linked to a heterologous promoter.
The specification only teaches how to make a recombinant Yeast cells to express the influenza HA and HIV Gag , wherein both of them can be expressed as a virus like particle. However, no any protective immune response have tested.
Therefore, the specification lack of sufficient teaching and evidence as well as adequate guidance for using a recombinant yeast cells as an oral vaccine.
The field is very unpredictable because while most yeasts used in food production are harmless, certain yeast cells, particularly Candida albicans, can be pathogenic to humans by causing infections or poisonous to life as evidenced by Mark Dwartzan et al. ( (2003). A Saccharomyces cerevisiae mutant with increased virulence. Proceedings of the National Academy of Sciences, 100(5), 2766-2770.
Hence, considering large quantity of experimentation needed, the unpredictability of the field, the state of the art, and breadth of the claims, it is concluded that undue experimentation would be required to enable the intended claim.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
/BAO Q LI/ Primary Examiner, Art Unit 1671
/BAO Q LI/Primary Examiner, Art Unit 1671
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