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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 07/14/2026 has been entered.
Claim 55 has been amended. Claims 58-62 have been newly canceled and no claims have been newly added.
Claims 55, 57, and 63 are currently pending and have been examined on their merits.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) and 35 U.S.C. 365(c), is acknowledged.
The claims have been examined with the effective filing date of the provisional 62/694849 which is 07/06/2018.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim(s) 55, 57 and 63 are rejected under 35 U.S.C. 103 as being unpatentable over June (US 6632789-from IDS filed 07/28/2021) in view of Schade et al (Blood, 2008) and Kirkland et al (WO 2015/116735-from IDS filed 06/25/2021).
Regarding claims 55, 57 and 63, June teaches and suggests methods for inhibiting T cell responses wherein an agent, such as quercetin, is used to down modulate the immune response in a transplant recipient of an organ or bone marrow graft (bone marrow is an organ graft) by contacting the graft with an agent (such as quercetin) that inhibits phosphatidylinositol 3-kinase (column 3 lines 10-29, column 5 lines 54-65, column 8 lines 1-20). June also teaches an embodiment wherein the T cells (a blood cell graft) are contacted with both an inhibitor of phosphatidylinositol 3-kinase and an inhibitor of a protein tyrosine kinase inhibitor (column 2 lines 51-57). A preferred protein tyrosine kinase inhibitor is one which inhibits src protein tyrosine kinases (column 6 lines 1-14). June teaches wherein the bone marrow is contacted with the agent as a pretreatment to inhibit graft versus host disease (column 8 lines 10-17).
June teaches that the subjects of their method include mammals, such as humans (column 6 lines 59-61) and that the transplants are allogeneic (column 7 line 57-column 8 line 16). Allogeneic transplants involve the transplantation of cells from one individual to another individual of the same species and thus an allogeneic transplant to a human subject includes a human donor.
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to include human donors and human recipients in their method because June suggest both as suitable and desirable for use in their method.
June do not include an embodiment wherein the donor graft is an organ treated with a composition containing an agent, such as dasatinib.
Schade disclose that dasatinib is a small-molecule protein tyrosine inhibitor that inhibits T-cell activation and proliferation and is useful in therapeutic opportunities to address autoimmune diseases, graft versus host disease (GVHD) and transplant allograft rejection with SFK inhibitors (Title, abstract, page 1366). Dasatinib inhibits src protein tyrosine kinases (abstract, page 1366).
Kirkland disclose that immune disorders or conditions that may be treated with a senolytic combination include conditions resulting from a host immune response in an organ transplant (such as bone marrow or other organs), such as a rejection of the transplanted organ. These senolytic combinations may be used for treating or reducing the likelihood of graft-versus-host disease in an organ transplant patient (page 45 lines 3-7). The combinations include an agent that inhibits Src kinase-such as dasatinib- and an agent that is a flavonoid-such as quercetin (page 8 lines 26-28). The use of in vitro cells assays are taught to characterize senolytic combinations and the biological sample used to establish the effectiveness of reducing the senescent cells can be bone marrow, tissue explant, organ culture or any other tissue or cell preparation from a subject and wherein the subject is human (page 32). The combination of dasatinib and quercetin is shown to reduce senescent cells in donor cells in vitro by 50% (page 89, Example 7).
One of ordinary skill in the art would have been motivated to administer both quercetin and dasatinib to the donor graft of June prior to providing the donor graft to the recipient because June suggest an embodiment wherein the graft is contacted with both an inhibitor of phosphatidylinositol 3-kinase and an inhibitor of a protein tyrosine kinase and Schade teach that dasatinib is a protein tyrosine kinase inhibitor that is beneficial and useful in therapeutic methods addressing autoimmune diseases, GVHD and transplant allograft rejection. One of ordinary skill in the art would have had a reasonable expectation of success because June indicate that an embodiment of their method will include an agent, such as quercetin, and a protein tyrosine kinase inhibitor, preferably of the SRC family (column 2 lines 55-60, column 6 lines 1-14) and dasatinib is a protein tyrosine kinase inhibitor of the SRC family tyrosine kinases as per Schade (page 1366).
One of ordinary skill in the art would have had additional motivation to treat donor organs with a combination of dasatinib and quercetin because Kirkland teach and suggest that this combination can be useful for the recipients of organ transplants to reducing the likelihood of graft-versus-host disease in an organ transplant patient (page 45 lines 3-7). One of ordinary skill in the art would have had a reasonable expectation of success because Kirkland show that the combination of dasatinib and quercetin reduce the number of senescent cells by 50% when contacted in vitro directly with human donor cells (page 89 Example 7) and indicate that this combination would be beneficial and suitable for organ transplant recipients such as those receiving bone marrow transplants (page 45 lines 3-7) and June is also treating bone marrow for transplant recipients as well.
Therefore, the combined teachings of June, Schade et al and Kirkland et al render obvious Applicant’s invention as claimed.
Response to Arguments
Applicant's arguments filed 06/22/2026 have been fully considered but they are not fully persuasive. Applicant’s arguments have been addressed in so far as they relate to the new rejection above.
Applicant’s amendments to the claims have overcome the rejections over Airau under 35 USC 102 and 35 USC 103 and therefore these rejections have been withdrawn.
Applicant argues that the combination of June and Schade does not teach or suggest the claimed invention. Applicant asserts that June is limited to inducing T cell unresponsiveness to an antigen in vivo or in vitro and refer to column 7 lines 57-61, column 7 line 65-column 8 line 9 and column 8 lines 10-17 of June. Applicant argues that the in vivo administration of an agent to a subject does not teach or suggest the claimed invention to a person having ordinary skill in the art.
This is not found persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In the current case, June teaches and suggests the treatment of grafts with an agent, such as quercetin, prior to implantation into a recipient to modulate the immune response in a transplant recipient. The teachings of Schade and Kirkland are relied upon for the motivation and reasonable expectation of success in contacting organ grafts in vitro with both quercetin and dasatinib prior to administering the contacted graft into the recipient as described above.
Applicant asserts that June is limited to a method of obtaining a transplant recipients own T cells, contacting them in vitro with the disclosed antigen and agent to induce antigenic unresponsiveness and then readministering the transplant recipient’s T cells back into the transplant recipient and that this does not teach or suggest the method of claim 1.
This is not found persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In the current case, June teaches and suggests the treatment of grafts with an agent, such as quercetin, prior to implantation into a recipient to modulate the immune response in a transplant recipient. The teachings of Schade and Kirkland are relied upon for the motivation and reasonable expectation of success in contacting organ grafts in vitro with both quercetin and dasatinib prior to administering the contacted graft into the recipient as described above.
In addition, the claimed method does not exclude wherein the donor and the recipient are the same person and the transplant is autologous.
Applicant asserts that contacting bone marrow that includes residual T cells in vitro with the bone marrow recipients own allogenic cells and an agent that inhibits D-3 phosphoinositide production to induce unresponsiveness in the donor T cells to recipient alloantigens does not suggest the claimed method.
This is not found persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In the current case, June teaches and suggests the treatment of grafts with an agent, such as quercetin, prior to implantation into a recipient to modulate the immune response in a transplant recipient. The teachings of Schade and Kirkland are relied upon for the motivation and reasonable expectation of success in contacting organ grafts in vitro with both quercetin and dasatinib prior to administering the contacted graft into the recipient as described above.
In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA J SCHUBERG whose telephone number is (571)272-3347. The examiner can normally be reached 8:30-5:00 EST.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631
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