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 .
Response
Applicant’s response and amendment election filed on May 26, 2026 have bene acknowledged. in the reply filed on 12/04/2025 is acknowledged.
Claims 1, 7, 9, 10, 11-13, 15, 20-21, 23 and 25 are amended. The new claims 32-57 are added.
Claims 1-4, 6-25, 30-57 ar pending and considered.
Claim Objections
The objection of claim 14 has been removed necessitated by Applicants’ amendment.
Claim Rejections - 35 USC § 112
The rejection of Claim 1 has bene removed necessitated by Applicants’ amendment.
The rejection of Claim 5 has bene removed due to the cancellation of the claims.
The rejections of claims 12-1, 20-21, 23 and 25 all have bene removed necessitated by Applicants’ amendment.
The rejection of Claim 15 has bene removed necessitated by Applicants’ amendment.
The rejection of claims 12-13 and 23 has bene removed necessitated by Applicants’ amendment.
Claim Rejections - 35 USC § 102
(Moot), The rejection of Claims 1-2, 6-8, 14-15, 18-19, 22-23 and 24-25 under 35 U.S.C. 102 a) (1) as being anticipated by WO 201732547A1 to Robert Petit et al. are moot in view of a new ground of rejection.
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.
Claims 1-15, 17-25, 31-36 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential structural cooperative relationships of elements, such omission amounting to a gap between the necessary structural connections. See MPEP § 2172.01. The omitted structural cooperative relationships are: what are the relationship between the least 5 neo-epitopes and the malignant neoplasm of the patient, because it is unclear if the at least 5 neoepitope s are isolated from the patents with the malignant neoplasm or a common neoepitopes presented in state of art because there is no teaching how these 5 epitopes are identified.
Moreover, the claims are vague and indefinite in that the metes and bounds of the molecular structures of the epitopes are not clearly defined.
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 1-15, 17-25, 31-36 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 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.
In the instant case, the claimed are directed to a method for making a composition for treating an individual suffering an any at least 5 epitopes without any descriptions of the molecular structures and functions.
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).
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.
Therefore, absent a detailed and particular description of a representative number, or at least a substantial number of the members of the genus of nucleic acid molecules, the skilled artisan could not immediately recognize or distinguish members of the claimed genus of nucleic acid sequences. Moreover, since the specification has not identified which nucleic 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.
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 1-4, 6-15, 17-20, 21- 25, 30-36 and 37-57 are rejected under 35 U.S.C. 103 as being unpatentable over WO2017132547A1 by Robert Petit et al. further in view of Ho et al. (Cancer Immunol. Therapy, 2013, Vol. 62, pp. 787-799) particular for claims 9-11 and Obata et al. (Life Sciences, 2002, Vol. 71, pp. 2083-2103).
The rejected claims are drawn to a method of inducing a therapeutic or ameliorating immune response against a malignant neoplasm in a patient, wherein cells of the malignant neoplasm express genetic material that encode neo-epitope containing polypeptides, the method comprising administering to the patient at least one effective dosage of a composition comprising:
1) at least one DNA expression vector, which comprises nucleic acid(s) encoding at least one polypeptide, which exhibits one or more neo-epitopes of the malignant neoplasm, and
2) a pharmaceutically acceptable carrier, diluent, or excipient, whereby somatic cells in the patient are brought to express the nucleic acid(s) encoding the at least one polypeptide, wherein the DNA expression vector comprises or encodes at least one Immune Stimulatory Sequence (ISS), wherein the effective dosage contains between 0.1 pg and 25 mg of the expression vector.
More preferably, the pharmaceutically acceptable carrier, diluent, or excipient is an aqueous buffered solution, which comprises an immunologically active and pharmaceutically acceptable amount of a stimulant of ISS acts through Toll-like receptor 3 (TLR-3) and/or MDA5 and/or RIG-I and or TLR-9. The composition further comprises poly I:C or poly IC;U12 cited in preferred 9-11 only.
Moreover, the composition comprises at least one DNA expression vector, which comprises nucleic acid(s) encoding at least one polypeptide, which exhibits one or more neo-epitopes of the malignant neoplasm, and at least one ISS encoding sequence. Still further, the expression vector encodes a plurality of peptides, where at least one exhibit(s) several encoded neo-epitopes.
Robert Petit et al. teach an immunotherapy delivery vector comprising one or more heterologous peptides comprise one or more heterologous sequence encoding one or more or even 1-20 immunogenic neo-epitopes for one or more tumors or cancers (Claims 1-9), wherein the multiple heterologous peptides are operably linked to each other via one or more peptide linkers or one or more 4x glycine linkers. Moreover, The immunogenic composition also comprises an adjuvant (paragraph V) selected from a group consisting of a granulocyte/macrophage colony-stimulating factor (GM-CSF) protein, a nucleotide molecule encoding a GM-CSF protein, saponin QS21, monophosphoryl lipid A, an unmethylated CpG-containing oligonucleotide (Claim 4 and paragraphs 40 and paragraphs 00161, 0034, 00488] and pharmaceutical acceptable carrier [Paragraph 00463].
More important, the cited reference also teaches a method for making the cancer vaccine that comprises the steps that the rejected claims looks so much similar or obvious to be arrived. For instant, A process for creating the immunotherapy delivery vector of any one of expression vector described previously in claims 1-37 that is personalized for a subject having a disease or condition, comprising:
(a) comparing one or more open reading frames (ORFs) in nucleic acid sequences extracted from a disease-bearing or condition-bearing biological sample from the subject with one or more ORFs in nucleic acid sequences extracted from a healthy biological sample, wherein the comparing identifies one or more nucleic acid sequences encoding one or more peptides comprising one or more immunogenic neo-epitopes encoded within the one or more ORFs from the disease-bearing or condition-bearing biological sample, wherein at least one of the one or more nucleic acid sequences comprises one or more frameshift mutations and encodes one or more frameshift-mutation-derived peptides comprising one or more immunogenic neo-epitopes; and
(b) generating an immunotherapy delivery vector comprising a nucleic acid comprising an open reading frame encoding a recombinant polypeptide comprising the one or more peptides comprising the one or more immunogenic neo-epitopes identified in step (a). (Claims 41-45).
Paragraph [00689] also teaches that the DNA expression vector comprises neo-epitopes , wherein each of them is connected with a linker sequence to the following neo- epitope encoded on the same vector. The final neo-epitope in an insert is fused to a TAG sequence followed by a stop codon. The TAG fused is set forth in SEQ ID NO: 57, a C- terminal SIINFEKL and 6xHis amino acid sequence. The TAG allows for easy detection of the tLLO-neo-epitope during for example secretion from an expression vector or when testing construct for affinity to specific T-cells, or presentation by antigen presenting cells. The linker is 4Xglycine DNA sequence, selected from a group comprising Gl-Gl l (SEQ ID NOS: 46-56) accordingly, or any combination thereof.
The cited reference also teaches at [00498] that in another embodiment, are administered to a subject by any method known to a person skilled in the art, such as parenterally, paracancerally, transmucosal, transdermally, intramuscularly, intravenously, intra-dermally, subcutaneously, intra-peritoneally, intra- ventricularly, intra-cranially, intra- vaginally or intra-tumorally.
Moreover, the cited reference at paragraph [00501-00503] also teaches that in one embodiment, a subject is administered a dose of the any of the compositions of the present disclosure every 1-2 weeks, every 2-3 weeks, every 3-4 weeks, every 4-5 weeks, every 6-7 weeks, every 7-8 weeks, or every 9-10 weeks in order to achieve the intended elicitation of an immune response targeted at the subject' s disease or condition. In one embodiment, a subject is administered a dose of the any of the compositions of the present disclosure every 1-2 months, every 2-3 months, every 3-4 months, every 4-5 months, every 6-7 months, every 7-8 months, or every 9-10 months in order to achieve the intended elicitation of an immune response targeted at the subject' s disease or condition.
Cho et al. teach that therapeutic vaccines for the treatment of cancer are an attractive alternative to some of the conventional therapies that are currently used. More importantly, vaccines could be very useful to prevent recurrences when applied after primary therapy. Unfortunately, most therapeutic vaccines for cancer have performed poorly due to the low level of immune responses that they induce. Previous work done in our laboratory in cancer mouse models demonstrated that vaccines consisting of synthetic peptides representing minimal CD8 T-cell epitopes administered i.v. mixed with poly-IC and anti-CD40 antibodies (TriVax) were capable of inducing massive T cell responses similar to those found during acute infections. We now report that some peptides are capable of inducing similarly large T cell responses after vaccination with poly-IC alone (BiVax). The results show that amphiphilic peptides are more likely to function as strong immunogens in BiVax and that systemic immunizations (i.v. or i.m.) were more effective than local (s.c.) vaccine administration. The immune responses induced by BiVax were found to be effective against established tumors in two mouse cancer models. The roles of various immune-related pathways such as type-I IFN, CD40 co-stimulation, CD4 T cells, TLRs and the MDA5 RNA helicase were examined. The present findings could facilitate the development of simple and effective subunit vaccines for diseases where CD8 T cells provide a therapeutic benefit (See abstract and section of Discussion.
Obata teaches a Tyrode’s buffer comprising 140 mM NaCl, 6 mM KCl, 3 mM CaCl2, 2 mM MgCl2, 10 mM 4-(2-hydroxyethyl)-1- piperazineethanesulfonic acid (Hepes) pH 7.4, and 10 mM glucose (See pages 2086, last paragraph).
While the cited reference does not teach at least one DNA expression vector expresses at least 5 neo-epitopes and also the effective dosage contains between 0.1 pg and 25 mg of the expression vector as well as particular, but multiple epitopes disclosed by the cited reference meets the limitation of at least 5 epitopes . However, it is noted that The modification of the incubation time for overnight to 40 to 190 hours range is generally recognized as being within the level of the ordinary skill in the art, In re Rose, 105 USPQ 237 (CCPA 1995) because it has been held that where the general conditions of a claim are disclosed in the prior art, discovering the workable ranges involves only routine skill in the art, In re Aller, 105, USPQ 233. Hence, the claimed invention as a whole is prima facie obvious for any person ordinarily skilled in the art.
Therefore, it would have been obvious for a person ordinarily skilled in the art to be motivated by the cited references to combine the teachings with the methods taught by the cited references to arrive the claimed method to make a composition for treating a patient suffering a cancer with his or her personal cancer therapeutic vaccine comprising the patient’s own cancer epitopes in combination of T cell activation adjuvant of CpG and poly I;:C for obtaining an enhanced T cell response against the cancer with a reassemble expectation of success as they are clearly taught by the cited references by Roberts et al and Ho et al. for an enhanced immune response by using T cell activation adjuvants of ISS optionally in combination with Poly I:C in a well-established Tyrode’s buffer prior to the current Application was filed.
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.
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BAO Q. LI
Examiner
Art Unit 1671
/BAO Q LI/Primary Examiner, Art Unit 1671
/BAO Q LI/Primary Examiner, Art Unit 1671
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