DETAILED ACTION
Claims 1-22 are pending. Of these, claims 1-6, 12, 16-17, and 21-22 are withdrawn as directed to a nonelected invention. Therefore, claims 7- 11, 13-15, and 19-20 are under consideration on the merits.
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/Restriction
Applicant’s election of Group I is acknowledged. The election having been made without traverse, the restriction requirement is still considered proper and is made FINAL.
Applicant’s election of cancer as the species of treatment is acknowledged. Since Applicant did not point to any alleged deficiencies in the election of species requirement, the election has been treated as having been made without traverse. The election of species requirement is still considered proper and is made FINAL.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/12/2023 was filed prior to the mailing date of a first Action on the merits. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, it was considered by the Examiner.
Claim Objections
Claim 9 is objected to because of the following informalities:
The claim recites the abbreviation “NK” without identifying the abbreviation. The first appearance of an abbreviation should be accompanied by the fully spelled out term. Correction is required.
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 8-9 and 12-15 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as 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 8 recites that the induction of immunity comprises the “in vivo and in vitro activation and differentiation of dendritic cells.” The recitation of “in vitro” renders the claim indefinite, because base claim 7 requires that the medicament is administered “to a subject in need,” meaning that it is in vivo and not in vitro. Clarification is required. For the purpose of examination in view of the prior art, claim 8 has been given its broadest reasonable interpretation, which is that the medicament is capable of activation and differentiation of dendritic cells in vitro.
Claim 9 recites “enhancing the cytotoxic activity of NK cells or the activity of cytotoxic T cells at the tumor site,” which is indefinite because no definition is provided for “enhancing,” e.g., what is the metric for measuring cytotoxic activity and its enhancement? Enhanced with respect to what? Clarification is required.
Claim 12 recites “enhancing of a specific humoral immune response against viral antigens,” which is indefinite because no definition is provided for “enhancing,” e.g., what is the metric for measuring humoral immune response against viral antigens and its enhancement? Enhanced with respect to what? Clarification is required.
Claim 13 recites “enhances the effect of a vaccine used in cancer immunotherapy,” which is indefinite because no definition is provided for “enhancing,” e.g., what is the metric for measuring the effect of a vaccine and its enhancement? Enhanced with respect to what? Clarification is required. Since dependent claims 14-15 do not clarify the point of confusion, they are also rejected
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 7-11 are rejected under 35 U.S.C. 102(a)(1) as anticipated by Perea et al. (Cancer Research 64, 7217-7129, October 1, 2004; of record in IDS).
As to claims 7-11, Perea discloses a chimeric peptide comprising the cell penetrating peptide Tat (GRKKRRQRRRPPQ) and peptide P15 (CWMSPRHLGTC) that are connected via a disulfide bridge between their cysteine residues so as to form the peptide SEQ ID NO: 1 of the claims (see “Design and Synthesis of Peptide Chimeras” section on page 7127). Perea further discloses a method of treating cancerous tumors by administering a therapeutically effective amount of the chimeric peptide, and teaches that the method induced cellular toxicity in vitro in a variety of tumor cell lines including mouse lung HPV16 transformed cells, human non-small-cell lung cancer, human small-cell lung cancer, human cervical carcinoma, and human T-cell leukemia (see Table 1) as well as shrinking tumor mass in vivo in a mouse bearing established solid tumors (Abstract and Figure 3). Perea teaches that the chimeric peptide inhibits phosphorylation of Protein Kinase 2 (CK2), which is frequently dysregulated in many human tumors and is known to play a determinant role in cell growth and proliferation (Abstract and Introduction section on page 7127).
The Perea method will necessarily and inherently induce antitumor and antiviral immunity mediated by immunogenic cell death as recited by claim 7, and the activation and differentiation of dendritic cells (claim 8), and enhance the cytotoxic activity of NK cells or cytotoxic T cells at the tumor site (claim 9) and cause a reversion of immunosuppressive to immunostimulatory tumor microenvironment (claim 10) and increase the secretion of pro-inflammatory cytokines (claim 11), because the method comprises the administration of the same medicament recited by the claims, and a composition cannot be separated from its properties. The U.S. Patent Office is not equipped with analytical instruments to test prior art compositions for the countless ways that an Applicant may present previously unmeasured characteristics. When the prior art appears to contain the same ingredients that are disclosed by Applicants' own specification as suitable for use in the invention, a prima facie case of anticipation or obviousness has been established, and the burden is properly shifted to Applicants to demonstrate otherwise. See MPEP 2112.01.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 7-11, 13-15, and 19-20 are rejected under 35 U.S.C. 103 as unpatentable over by Perea et al. (Cancer Research 64, 7217-7129, October 1, 2004) in view of EP 1491553 (published 12.29.2004; of record in IDS) and Chen et al. (Cancers (2019), 11, 1909).
The teachings of Perea are relied upon as discussed above, but Perea does not further expressly disclose that the method enhances the effect of a vaccine used in cancer immunotherapy (claim 13) which is administered sequentially or simultaneously (claim 14), wherein the vaccine is based on dendritic cells, cytotoxic T cell, or tumor-infiltrating lymphocytes (claim 15), such as a PDL1 immune checkpoint inhibitor (claim 18) that is administered sequentially or simultaneously (claim 19) and wherein the PDL1 immune checkpoint inhibitor is an anti-PDL1 monoclonal antibody (claim 20).
EP1491553 discloses a peptide that binds and inhibits phosphorylation of Protein Kinase 2 (see peptide e. of claim 1 of EP1491553) and further teaches that the peptide may be chemically conjugated with Tat cell penetrating peptide (paragraph 25), wherein if the conjugation was achieved via a disulfide bond between the cysteine residues of the peptide and the Tat cell penetrating peptide, would be SEQ ID NO: 1 of the present claims. EP1491553 teaches that the peptide is useful for treating epithelial tumors such as those associated with HPV (Abstract) and expressly suggests combining the peptide with other agents such as therapeutic vaccines (paragraph 29).
Chen discloses that dendritic cells are potent antigen presenting cells that activate cellular and humoral immune responses, and that tumor vaccines based on dendritic cells have been found to be safe and potent in inducing anti-tumor-associated antigen immune responses in cancer patients, but that they have limited clinical efficacy so there is a need to enhance their potency, and that PD-L1 is a key immune checkpoint molecule commonly overexpressed on tumor cells allowing them to evade antitumor immune destruction, and that repeated administration of PDL1 antibodies has been found to induce sustained tumor regression in some patients (Abstract). Chen is directed to the discovery that the administration of a dendritic cell vaccine that is loaded with a PD-L1 immunogen was able to induce anti-PD-L1 antibody and T cell responses in mice and had cytolytic activity against PD-L1+ tumor cells (Abstract). Chen also teaches that a known alternative is to administer manufactured PD-L1 antibodies into cancer patients at 2-3 week intervals, and that administration of such PD-L1 inhibitors results in robust antitumor activities in some cancer patients (Discussion section on pages 9-10).
As to claims 13-15 and 18-20, it would have been prima facie obvious to one of ordinary skill in the art at the effective filing date of the present invention to modify the method of treating solid tumors taught by Perea by co-administering the chimeric peptide taught therein sequentially or simultaneously with a dendritic vaccine and/or a manufactured anti-PDL1 monoclonal antibody, because EP1491553 expressly suggests combining cancer-treating chimeric peptides very similar to those taught by Perea with other agents such as therapeutic vaccines, and Chen teaches that vaccines based on dendritic cells have been found to be safe and potent in inducing anti-tumor-associated antigen immune responses in cancer patients but have limited efficacy so co-administration with other compounds that are anti-PD-L1 therapeutics should be considered, and further that it is known to administer manufactured PD-L1 antibodies into cancer patients as an anti-PD-L1 inhibitor and that the administration of such inhibitors is known to have robust antitumor activities in some cancer patients, such that the skilled artisan would have been motivated to combine the administration of the Perea chimeric peptide with a dendritic vaccine and/or manufactured PD-L1 antibodies with a reasonable expectation of success in arriving at a method with improved therapeutic efficacy than if only one of these therapeutic agents was administered.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAREN GOTFREDSON whose telephone number is (571)270-3468. The examiner can normally be reached on M-F 9AM-6PM.
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/GAREN GOTFREDSON/Examiner, Art Unit 1619
/ANNA R FALKOWITZ/Primary Examiner, Art Unit 1600