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 to Applicants Arguments/Amendments
The amendments made to the instant set of claims have better clarified the invention. As a result of the amendments, the former 112(b) rejection is withdrawn. Because of the amendment, the former art rejection is withdrawn and a new art rejection put forward. The double patenting rejection is withdrawn due to the claim amendments.
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 1 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Qin (WO2019184459) in view of Heukamp “Indentification of the Three Non-VNTR MUC1-derived HLA-A*0201 Restricted T-Cell Epitopes that Induce Protective Anti-Tumor Immunity in HLA-A2/Kb Transgenic Mice” (Int J. Cancer, 91, 385-392 (2001), and Rooney (WO2018187356).
Qin teaches a pharmaceutical composition for inducing an immune response in a human or animal subject suffering from a pathological disease or disorder (cancer), comprising autologous activated cytotoxic CD8+ T lymphocytes (CTLs) (Abstract, Page 6, Page 8 of Qin) activated by autologous primed mature dendritic cells of the human or animal subject (Pages 1-2 and 6-8 of Qin), said autologous primed mature dendritic cells presenting an antigenic peptide (Pages 6-8 of Qin), wherein the activated CTLs are derived from an autologous population of peripheral blood mononuclear cells (PBMCs) isolated from peripheral blood of the same human or animal subject (Pages 6 and 8 of Qin); wherein the activated CTLs are able to recognize the antigenic peptide (Abstract, Page 6, and Page 8 of Qin); wherein the CTLs have been activated by the autologous primed mature dendritic cells presenting the antigenic peptide, wherein the dendritic cells have been isolated from the same human or animal subject as the CTLs (Pages 6 and 8 of Qin), wherein the CTLs have been activated by co-culturing CD8+ T cells derived from the population of PBMCs with the autologous primed mature antigen-presenting dendritic cells ex-vivo (Page 6, last paragraph and Page 8, first full paragraph) as in instant Claim 1.
Qin teaches that antigenic/immunogenic peptides can be delivered to T cells by autologous dendritic cells. Qin does not teach that the antigenic peptide consists of a MUC 79-87 peptide (SEQ ID: 1). Heukamp teaches that MUC 79-81 (consisting of SEQ ID:1) is an excellent immunogenic peptide that can trigger a strong cytotoxic T cell response (Abstract and Page 387, Immunogenicity of MUC1-derived peptides in A2/Kb transgene mice ) It would have been obvious to an artisan of ordinary skill at the time of effective filing to have used the antigenic peptide consisting of MUC 79-87 peptide of SEQ ID: 1 taught in Heukamp to activate CD8+ T cells. An artisan would have been motivated to have used such an antigenic peptide because the peptide MUC 79-87 “was found to be immunogenic in A2/Kb transgenic mice, in that they reproducibly induced strong peptide-specific CTL responses (Page 387, Section Immunogenicity of MUC1-derived peptides in A2/Kb transgenic mice, 2nd paragraph of Heukamp). The peptide MUC 79-87 produced CTL activity that was capable of eradicating MUC1 expressing tumor cells in vivo (Page 389, 1st full paragraph). Because the antigenic peptide MUC 79-87 can be used to successfully target and eradicate cancer cells, there would have been a high expectation for success (Page 389, 1st full paragraph) as in instant Claim 1.
Qin does not specify that the antigen presenting dendritic cells used to present the antigenic peptide are immature dendritic cells. However, Rooney teaches that immature dendritic cells can be used to present antigens (Paragraph 359 of Rooney). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have used immature dendritic cells to present the antigenic peptide. An artisan would have been motivated to have activated CD8+ T cells with an immature dendritic cell since such cells are effective antigen presenting cells (Paragraphs 357-359 of Rooney). Because this particular type of dendritic cell (immature dendritic cell) can effectively present antigens, there would have been a high expectation for success. As the antigen presenting cell presents antigen to the cytotoxic T cell, it becomes more mature due to the cytokine environment that it is in. The claim does not state a specific level of maturity or specific markers that are present at each stage of dendritic cell development as in instant Claim 1.
Dependent Claims taught by Qin
Qin teaches that its composition can be used for a treatment of cancer (Page 1 of Qin) as in instant Claim 14.
Qin teaches that a T cell composition can be activated by dendritic cells through the presentation of an antigenic peptide. Qin does not teach that the antigen is MUC 79-87 peptide from sequence 1. However, an artisan would have been motivated to have used the MUC (79-87) antigenic peptide from sequence 1 because that sequence portion is commonly found in tumor cells and that peptide sequence can activate CD8+ T cells. Administering such a peptide sequence assists the immune cells in targeting cancer cells. There would have been a strong motivation for using that precise antigenic MUC peptide because it is known to be able to assist immune cells such as cytotoxic T cells with successfully targeting cancer cells. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicants’ invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combinations would have yielded predictable results to one of ordinary skill in the art at the time of the invention (See KSR International Co. V. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people most likely will be knowledgeable and well-read in the relevant literature. These people will have practical knowledge in immunotherapy. Therefore, the level of ordinary skill in this art is high.
Response to Applicants Arguments---
Because of the recent amendments made to the claims, the examiner has withdrawn the McKenzie reference from the rejection.
Applicants further argue that none of the references teach the limitation, “activated by autologous primed mature dendritic cells of the human or animal subject” and “wherein the dendritic cells, prior to their use in the activation of CD8T+ cells by co-culturing, have been cultured ex vivo and subsequently have been primed in an immature state with antigenic peptide, and subsequently have been matured in the presence of a cytokine cocktail.” This limitation can be interpreted as stating that an immature cell is initially used/initially exposed to the CD8+T cell. Rooney teaches that “immature antigen presenting cells” can be initially presented to CD8+ T cells and that these immature dendritic cells can successfully deliver immunogenic antigens (Paragraphs 357-359 of Rooney). As the immature antigen presenting cells (APCs/dendritic cells) come into contact with the CD8+T cells, the APCs are becoming “more mature” with the interaction between the APCs and the CD8+T cells and there are multiple cytokines produced by these immune cells during such a maturation step. The instant claims do not specify a more clearer maturation path or require the presence of specific markers at certain time points.
Applicants further argue that the prior art does not teach an ex vivo dendritic cell/antigen presenting cell maturation process as recited in the instant set of claims. The instant claim recites the following, “wherein the dendric cells, prior to their use in the activation of CD8+ T cells by co-culturing have been cultured ex vivo and subsequently have been primed in an immature state with antigenic peptide, and subsequently have been mature in the presence of a cytokine cocktail.”
Pages 1-2 and 6-8 of Qin teaches the ex vivo culture process of dendritic cells and their exposure to antigen. Rooney is used to teach that CD8+ T cells can be stimulated by immature antigen presenting cells (Abstract, Paragraphs 3, 357-359 of Rooney). The abstract and Paragraphs 357-359 of Rooney are stating that immature dendritic cells can be used to successfully deliver immunotherapeutic peptides, nucleic acids encoding the peptides, or peptide binding agents to help with immunotherapy. Paragraph 3 of Rooney teaches that the delivered immunotherapeutic peptides, nucleic acid encoding the peptides, and peptide binding agents etc. can be considered types of tumor vaccines which in turn can stimulated CD8+T cells that recognize and lyse tumor cells. When the immature dendritic cells with the immunotherapeutic peptides come into contact with cytotoxic T cells, the immature dendritic cells will be able to present the immunotherapeutic peptides to the CD8+ T cells much in the same way that occurs during an ex vivo process in which CD8+ T cells are primed with antigen presenting cells/dendritic cells. While the immature dendritic cells/APCs of Rooney are pulsing the CD8+ T cells, cytokines are present which will further mature the cells.
Conclusion
All claims stand rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
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