DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 3/27/26 has been entered.
Election/Restrictions
Applicant’s election without traverse of invention I in the reply filed on 12/6/2024 is acknowledged.
Claims 47-52, 58 and 59 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 4/1/2022.
Claims 42-46 and 54-57 are examined on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 3/27/26 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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.
(New Rejection) Claims 42-46 and 54-57 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 42-46 and 54-57. 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, plasmid or a DNA expression vector.
With respect to the unisolated transgenes as “nucleic acids” or “plasmids” 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: 1, 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. 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, "nucleic acid", “plasmid” and “expression vector” 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 nucleic acid, plasmid 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 nucleic acid, plasmid 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.
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.
(New Rejections) Claims 43 and 54-57 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 43 recites, “a) a nucleic acid sequence that encodes a consensus Zaire ebolavirus envelope glycoprotein immunogen selected from the group consisting of: SEQ ID NO:64 (ZEBOV CON), a fragment of SEQ ID NO:64 that encodes 600 or more amino acids of SEQ ID NO:1, an amino acid sequence that is at least 95% identical to SEQ ID NO:64, a fragment of an amino acid sequence that is at least 95% identical to SEQ ID NO:64 that encodes 600 or more amino acids of SEQ ID NO:1; SEQ ID NO:64 (ZEBOV CON) linked to a nucleotide sequence encoding an IgE signal peptide, a fragment of SEQ ID NO:64 that encodes 600 or more amino acids of SEQ ID NO:1 operably linked to a nucleotide sequence encoding an IgE signal peptide, a nucleotide sequence that is at least 95% identical to SEQ ID NO:64 operably linked to a nucleotide sequence encoding an IgE signal peptide, and a fragment of an amino acid sequence that is at least 95% identical to SEQ ID NO:64 that encodes 600 or more amino acids of SEQ ID NO: 1 operably linked to a nucleotide sequence encoding an IgE signal peptide…”. SEQ ID NO: 64 is a nucleic acid sequence that encodes SEQ ID NO: 1. Therefore, the bolded text from above identifies unclear limitations of claim 43, part a) since amino acids are referred to when an nucleic acid sequence (SEQ ID NO: 64) is claimed. Part b) of claim 43 contains similar unclear limitations pertaining to SEQ ID NO: 65.
Claim 54 recites, “A nucleic acid molecule comprising a nucleotide sequence encoding a Filoviridae envelope glycoprotein immunogen, wherein the nucleotide sequence encodes a Marburg marburgvirus envelope glycoprotein immunogen selected from the group consisting of: SEQ ID NO:66 (MARV ANG), a fragment of SEQ ID NO:66 that encodes 600 or more amino acids of SEQ ID NO:3, an amino acid sequence that is at least 96% identical to SEQ ID NO:66, a fragment of an amino acid sequence that is at least 96% identical to SEQ ID NO:66 that encodes 600 or more amino acids of SEQ ID NO:3; SEQ ID NO:66 (MARV ANG) linked to a nucleotide sequence encoding an IgE signal peptide, a fragment of SEQ ID NO:66 that encodes 600 or more amino acids of SEQ ID NO:3 operably linked to a nucleotide sequence encoding an IgE signal peptide, a nucleotide sequence that is at least 96% identical to SEQ ID NO:66 operably linked to a nucleotide sequence encoding an IgE signal peptide, and a fragment of an amino acid sequence that is at least 96% identical to SEQ ID NO:66 that encodes 600 or more amino acids of SEQ ID NO: 3 operably linked to a nucleotide sequence encoding an IgE signal peptide.
SEQ ID NO: 66 is a nucleic acid sequence that encodes SEQ ID NO: 3. Therefore, the bolded text from above identifies unclear limitations of claim 54 since amino acids are referred to when an nucleic acid sequence (SEQ ID NO: 66) is claimed. Claims 55-57 are also rejected because they depend from claim 54, but do not remedy this deficiency.
Claim Rejections - 35 USC § 102
(Prior Rejection Withdrawn in view of Amendments) Claims 42 and 44-46 are rejected under pre-AIA 35 U.S.C. 102b as being anticipated by Blaney et al. (US PGPub 2014/0212434).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP §§ 706.02(l)(1) - 706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
(Prior rejections maintained)
Claims 42 and 44-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 and 14 of U.S. Patent No. 9597388 in view of Grogan et al. (US PGPub 2003/0108560). Although the claims at issue are not identical, they are not patentably distinct from each other because the patented invention and the instant invention both claim plasmid based compositions which possess obvious combinations of ebola and marburg virus sequences (SEQ ID NO:s 1-6), which are identical. In addition, Grogan et al. teach ebola virus nucleic acid and amino acid sequences and the use of vectors/plasmids for expressing the DNA sequence which encode these amino acid sequences in a cell. [see plasmids 46 and 48] Grogan et al. also teach that RNA molecules, such VEE replicons, which possess RNA sequences, can encode Ebola virus GPs. [see paragraphs 46-47 and 69-71] In addition, promoters can be operably linked to the nucleic acid sequences. [see paragraph 48] Specific examples of the nucleic acid and amino acid sequences, respectively, are SEQ ID NO: 11 and 12. SEQ ID NO: 12 is 98.8% identical to SEQ ID NO: 1 of the instant invention. Therefore, the patented inventions in view of Grogan et al. renders obvious the instant invention.
Claims 42 and 44-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 10,765,733 in view of Grogan et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because the patented invention and the instant invention both claim plasmid based compositions which possess obvious combinations of ebola and marburg virus sequences (SEQ ID NO:s 1-6), which are identical. In addition, the teachings of Grogan et al. summarized above render obvious the specific use of RNA or DNA sequences, which would possess promoters operably linked to the glycoprotein specific sequences that encode for SEQ ID NO:s 1-6 of the instant invention. Therefore, the patented inventions in view of Grogan et al. renders obvious the instant invention.
Claims 42 and 44-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 and 14 of U.S. Patent No. 10,034,930 in view of Grogan et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because the patented invention and the instant invention both claim plasmid based compositions which possess obvious combinations of ebola and marburg virus sequences (SEQ ID NO:s 1-6), which are identical. In addition, the teachings of Grogan et al. summarized above render obvious the specific use of RNA or DNA sequences, which would possess promoters operably linked to the glycoprotein specific sequences that encode for SEQ ID NO:s 1-6 of the instant invention. Therefore, the patented inventions in view of Grogan et al. renders obvious the instant invention.
Claims 42 and 44-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 and 11 of U.S. Patent No. 11,723,969 in view of Grogan et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because the patented invention and the instant invention both claim plasmid based compositions which possess obvious combinations of ebola and marburg virus sequences (SEQ ID NO:s 4-6), which are identical. In addition, the teachings of Grogan et al. summarized above render obvious the specific use of RNA or DNA sequences, which would possess promoters operably linked to the glycoprotein specific sequences that encode for SEQ ID NO:s 4-6 of the instant invention. Therefore, the patented inventions in view of Grogan et al. renders obvious the instant invention.
Claims 42 and 44-46 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, 13 and 16 of U.S. Patent No. 11091518 in view of Grogan et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other because the patented invention and the instant invention both claim nucleic acid sequences that encode the ebola virus glycoprotein of SEQ ID NO: 1. In addition, both inventions are drawn plasmids that comprise the nucleic acid sequence. In addition, the teachings of Grogan et al. summarized above render obvious the specific use of RNA or DNA sequences, which would possess promoters operably linked to the glycoprotein specific sequences that encode for SEQ ID NO: 1 of the instant invention. Therefore, the patented inventions in view of Grogan et al. renders obvious the instant invention.
Conclusion
No claims are allowed.
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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/BENJAMIN P BLUMEL/
Primary Examiner, Art Unit 1671
