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 invention I and the species of SEQ ID NO: 10 in the reply filed on 2/27/26 is acknowledged.
Claims 4-7, 12-21, 32 and 34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 2/27/26.
Claims 23-31 are withdrawn as they require non-elected species.
Claims 1-3, 8-11, 22 and 33 are examined on the merits.
Priority
Acknowledgment is made of applicant's claim for foreign priority to EP20190070.1 based on an application filed in the EPO on 8/7/2020. It is noted, however, that applicant has not filed a certified copy of the foreign application as required by 37 CFR 1.55. Therefore, the earliest priority date of the filing of the PCT, which was filed on 7/29/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/1/23 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Objections
Specification
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 through 1.825 for the reason(s) set forth: specification is objected to because figures 5 and 7 does not contain a specific SEQ ID NO:s for each amino acid sequence presented.
Applicants must comply with sequence rules in order to be considered a complete response to this Office Action.
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 8 and 9 are rejected under 35 U.S.C. 112, first paragraph, as containing subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Applicant broadly claims a host cell or expression vector or nucleic acid containing the nucleic acids of claims 8 and 9. The claims read on a cell within a transgenic animal or a transgene therein given that the term "isolated" is not denoted in describing the nucleic acid or expression vector.
With respect to the unisolated transgenes as “nucleic acids” or “expression vectors “of the instant claims discussed above, the state of the art at the time of filing was such that one of skill could not predict the phenotype of transgenics. The art of transgenic animals has for many years stated that the unpredictability lies, in part, with the site or sites of transgene integration into the target genome and that "the position effect" as well as unidentified control elements are recognized to cause aberrant expression of a transgene (Wall et Al., Theriogenology, Vol. 45, Pg. 57-68, 1996).
The elements of the particular construct used to make transgenic animals are also held to be critical, and they must be designed case by case without general rules to obtain good expression of a transgene; e.g., specific promoters, presence or absence of introns, etc. (Houdebine et Al., Journal of Biotechnology, Vol. 34, Pg. 269- 287, 1994). Furthermore, transgenic animals are regarded to have within their cells, cellular mechanisms that prevent expression of the transgene, such as methylation or deletion from the genome (Kappell et Al., Current Opinions in Biotechnology, Vol. 3, Pg. 548-553, 1992). Houdebine (Comparative Immunology, Microbiology, and Infectious Diseases, Vol. 32, Pg. 107-121, 2009) teaches progress has been made in the field of transgenic animals for production of foreign proteins (Abstract); however, constructing an efficient expression vector to produce a therapeutic protein is not a standard operation (Pg. 116, Paragraph, second). Therefore, undue experimentation is required to make and use a transgene and transgenic animal to produce the antibody and antibody fragments of the instant claims.
Examples in the literature aptly demonstrate that even closely related species carrying the same transgene construct can exhibit widely varying phenotypes. Mullins (1993, Hypertension, Vol. 22, No. 4, pp. 630-633) states that not all animals express a transgene sufficiently to provide a model for a disease as the integration of a transgene into different species of animal has been reported to give divergent phenotypes. For example, several animal models of human diseases have relied on transgenic rats when the development of mouse models was not feasible. Mullins (1990, Nature, Vol. 344, 541-544) produced outbred Sprague-Dawley x WKY rats with hypertension caused by expression of a mouse Ren-2 renin transgene. Hammer (1990, Cell, Vol. 63, 1099- 1112) describes spontaneous inflammatory disease in inbred Fischer and Lewis rats expressing human class I major histocompatibility allele HLA-B27 and human 02- microglobulin transgenes. Both investigations were preceded by the failure to develop human disease-like symptoms in transgenic mice expressing the same transgenes that successfully caused the desired symptoms in transgenic rats (Mullins, 1989, EMBO J., Vol. 8, pages 183-191). Thus, the use of nonmurine species for transgenesis will continue to reflect the suitability of a particular species for the specific questions being addressed, bearing in mind that a given construct may react very differently from one species to another.
The examiner notes here, in addition to these issues, even assuming arguendo a person having ordinary skill in the art could make a host organism with functional transgene that encodes the instantly recited SEQ ID NO: 10, there is no predictability that the host will survive its expression. The transgene depends on the host for function and harm to the host, including death, renders the transgene nonfunctional and thus not enabled.
The art is well-aware of side effects caused by expressing proteins, such as therapeutic antibodies. In a transgenic cell or animal that expresses the same, the antibody will exert any possible side effect it can. It is not administered but chronically present and so such side effects are chronic and potentially more serious than any from an administered antibody. Hansel (Nature Reviews Drug Discovery, Vol. 9, Pg. 325-337, 2010) teaches in their table 1 on page 328 numerous exemplary side effects from licensed monoclonal antibodies to include: increased bleeding risk, infection, heart failure, cancer, thyroid disorder, autoimmune reactions, and cytokine release syndrome (CRS) to name only a few. One or more such effects, or similar, may occur with the therapeutic antibody instantly recited when administered and indeed be exacerbated by chronic exposure due to internal expression. The instantly encoded antibody binds a mammalian protein and so may very well target related or unrelated proteins in the transgenic host, leading to such side effects. For all these reasons, previously raised and new, transgenes are not enabled.
At the time of filing, the phenotype of a transgene and transgenic cell contained within any animal was unpredictable. The claims as written, encompassing a transgene and cell in a transgenic animal, is not adequately described in the specification as to prevent excessive experimentation by the public to generate and use the invention. Applicants can obviate the instant rejection by amending the claim to recite the term "isolated" before the recitation, "host cell" and by amending the vector and polynucleotide claims to specify they are not in a transgenic animal. Applicant may consider using purified in such claims if description is appropriate for such a term and it is not redefined away from standard meaning. Method claims using these products should also carry the appropriate adjectives above.
In view of the lack of the predictability of the art to which the invention pertains as evidenced by the art above, the lack of guidance and direction provided by Applicant, and the absence of working examples, undue experimentation would be required to make and use transgenic animals possessing the claimed host cells, nucleic acid, or expression vector, with a reasonable expectation of success, absent a specific and detailed description in Applicant’s specification of how to effectively practice this and absent working examples providing evidence which is reasonably predictive that the claimed host cell, nucleic acid, or expression vector, commensurate in scope with the claimed invention. The same can be said for the transgenes and transgenic animals encompassed by the instant claims. Thus, the claims are rejected here.
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)(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.
Claim(s) 1-3, 8-11, 22 and 33 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Singh et al. (US PGPub 2023/0201332).
The claimed invention is drawn to a peptide comprising SEQ ID NO: 10, variant sequences thereof which are at least 88% homologous to SEQ ID NO: 10, and wherein said variant binds to molecule(s) of the major histocompatibility complex (MHC) and induces T-cells cross-reacting with said variant peptide; and a pharmaceutical acceptable salt thereof, wherein said peptide is not a full-length polypeptide. The peptide is configured to bind to an MHC class-I or -II molecule, and wherein said peptide when bound to said MHC, is capable of being recognized by CD4 and/or CD8 T-cells. [claims 1-3]
With regard to the claimed limitations of wherein said variant binds to molecule(s) of the major histocompatibility complex (MHC) and induces T-cells cross-reacting with said variant peptide; and a pharmaceutical acceptable salt thereof, wherein said peptide is not a full-length polypeptide and that the peptide is configured to bind to an MHC class-I or -II molecule, and wherein said peptide when bound to said MHC, is capable of being recognized by CD4 and/or CD8 T-cells. MPEP 2112 II states, INHERENT FEATURE NEED NOT BE RECOGNIZED AT THE RELEVANT TIME, therefore, if the prior art teaches a peptide that meets the structural requirements of the claimed invention, any of these claimed properties are inherent.
The claimed invention also requires a nucleic acid encoding for the peptide or variant, and the nucleic acid is in an expression vector, which is in a recombinant host cell, such as an antigen presenting cell, a dendritic cell, a T-cell or an NK cell. [claims 8-11]
The peptide is also part of a pharmaceutical composition, which also comprises a pharmaceutically acceptable carrier. [claim 21]
The claimed invention is also drawn to a kit comprising: (a) a container comprising a pharmaceutical composition containing the peptide or the variant of SEQ ID NO: 10, in solution or in lyophilized form;
(b) optionally, a second container containing a diluent or reconstituting solution for the lyophilized formulation;
(c) optionally, the peptide of SEQ ID NO: 10, and
(d) optionally, instructions for (i) use of the solution or (ii) reconstitution or use of the lyophilized formulation. [claim 33] However, these optional limitations are interpreted as not being specifically required by the claimed kit.
Therefore claim 33 is drawn to a kit comprising: (a) a container comprising a pharmaceutical composition containing the peptide or the variant of SEQ ID NO: 10, in solution or in lyophilized form.
Singh et al. teach the use of neurotoxin associated proteins (NAPs) of botulinum neurotoxin (BoNT) produced by Clostridium botulinum as delivery vehicles (e.g. adjuvants or carrier or protectant or bioenhancer) of the vaccine for oral/sublingual, and/or intranasal administration. [see paragraph 13] Therefore, Singh et al. teach the use of pharmaceutically acceptable carriers. In addition, based on Singh et al. teaching that their compositions are to be administered intranasally, this act would require the use of a container that possessed the vaccine composition in a solution. They also teach peptide compositions from SARS-CoV-2 proteins, such as SEQ ID NO: 45 (FYSKWYIRVGARKSAPLIEL), which comprises all of SEQ ID NO: 10 (see bolded text). [See Table 6] Singh et al. also teach at claims 1, 3 and 11 a mutated recombinant DrTeNT-CoV2 (TC2) vaccine composition comprising one or more detoxified forms of a whole or part of a tetanus neurotoxin (DrTeNT) proteins, with one or more (TC2) epitopes and/or domains derived from a toxin, a pathogen, or a disease, embedded or chemically attached to said DrTeNT proteins. This mutated recombinant DTeNT-CoV2 (TC2) vaccine is either a DNA or a plasmid or a protein vaccine and the epitope is at least 85% identical to SEQ ID NO: 45.
In addition, Singh et al. teach expression vectors and cells that comprise these vectors, such as APCs. [see paragraphs 24-26]
Therefore, Singh et al. anticipate the instant invention.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BENJAMIN P BLUMEL whose telephone number is (571)272-4960. The examiner can normally be reached M-F 8-5 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Allen can be reached at (571) 270-3497. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BENJAMIN P BLUMEL/Primary Examiner, Art Unit 1671
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