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 .
Claim Status
Claims 1-8 are pending.
Claims 1-8 have been examined.
Priority
This application is a 371 of PCT/EP2021/085062 filed on 12/09/2021 and claims foreign priority of EP 20306528.9 filed on 12/10/2020.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/9/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Objections
Claims 1-7 are objected to because of the following informalities:
Claim 1 contains the acronym “MAIT”, and an acronym in the first instance of claims should be expanded upon/spelled out as “mucosal-associated invariant T” with the acronym indicated in parentheses as (MAIT). The abbreviations can be used thereafter.
Claim 2 is objected to due to missing a comma “,” between the claim number and the word of “wherein”. Claim 2 should be revised to “The method of claim 2, wherein….” with the format in claim 8.
Similarly, claims 3-7 are objected to due to missing a comma “,” between the claim number and the word of “wherein”. Claims 3-7 should be revised by adding a comma “,” between the claim numbers and the word “wherein” with the format in claim 8.
Claim 4 is further objected to the word of “subject” in line 1. Claim 4 should be revised by replacing the word “subject” with the word “patient”.
Appropriate correction is required.
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.
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.
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.
Claims 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Magnani et al. (WO 2017/079,215 A1) in view of Gao et al. (Blood. (2019) 134 (Supplement 1): 2001) and Varelias et al. (J Clin Invest. 2018;128(5):1919-1936, cited in IDS 6/9/2023).
Claim 1 is drawn to a method of controlling Graft Versus Host Disease (GVHD) in a patient after transplantation comprising administering to the patient a therapeutically effective amount of a population of MAIT cells.
Magnani et al. teach hematopoietic cell transplantation is a promising therapeutic approach in the treatment of hematologic diseases, disorders, or conditions (e.g., thalassemias, sickle cell disease, leukemias, lymphomas, myelomas) as well as in rescue from chemotherapy and high-dose radiation such as cancer therapy [p2, 004; p38, 0114]. Magnani et al. teach, a patient may avoid reintroducing diseased cells from his own autologous donation into his system by using allogenic cells (reading allogeneic hematopoietic cell transplantation), but risks such complications as graft-versus-host disease (GVHD) [p2, 004].
Magnani et al. do not teach administering a therapeutically effective amount of a population of MAIT cells to control Graft Versus Host Disease (GVHD) in the patient after transplantation.
Gao et al. teach gut graft-versus-host disease (GVHD) is a serious complication after hematopoietic stem cell transplantation (HSCT) and is associated with high mortality. Mucosal-associated invariant T cells (MAIT) are a group of innate-like T cells enriched in the intestine, which may alter the composition of the intestinal microflora or exert a certain immunomodulatory effect to protect the intestinal mucosa from further damage for the inflammatory response known in the art (p1, Background & Purpose). Gao et al. teach the total number of infused MAITs in the graft of gut GVHD patients was significantly lower than that of no GVHD patients (p1, Results to p2, para 2). Gao et al. further show gut GVHD was more likely to occur in patients who were infused with a smaller number of MAIT cells in grafts (p2, Fig. 1), suggesting the potential functional effects of MAIT cells on gut GVHD. Gao et al. further suggest MAIT cells may function through direct immunosuppression or regulation of intestinal microflora (p2, Conclusion).
Similarly, Varelias et al. teach “Recipient mucosal-associated invariant T cells
control GVHD within the colon” (Title) consistent with Gao’s suggestion. Varelias et al. teach
MAIT cells are present in small but definable numbers in graft-versus-host disease (GVHD)
target organs and protect from acute GVHD in the colon following bone marrow transplantation (BMT). Varelias et al. teach recipient MAIT cells abrogate GVHD induced by allogeneic stem
cell transplantation and further suggest any effect on survival was due to the absence of MAIT cells alone (p1923, col 1, last para to col 2, last line 4-5; Fig 1 A and B). Varelias et al. further teach in order to regulate disease during GVHD, recipient MAIT cells must survive conditioning and the incoming alloreactive donor graft in the early transplant period (p1924, col 2, para 1).
Because (a) Gao et al. teach infused MAIT cells in the graft of gut GVHD patients significantly lower than that of no GVHD patients (p1, Results to p2, para 2) and (b) Varelias et al. teach MAIT cells abrogate GVHD induced by allogeneic stem cell transplantation and further suggest any effect on survival was due to the absence of MAIT cells alone (p1923, col 1, last para to col 2, last line 4-5; Fig 1 A and B), one of ordinary skill in the art would have found it obvious to administer an effective amount of MAIT cells taught by Gao et al. in view of Varelias et al. to reduce the risk of developing complications of graft-versus-host disease GVHD for Magnani’s patients after allogeneic hematopoietic cell transplantation, reading on controlling Graft Versus Host Disease (GVHD) in a patient after transplantation comprising administering to the patient.
One of ordinary skill in the art before the effective fining date of this invention would have found it obvious to combine (i) Magnani et al. and (ii) Gao et al. in view of Varelias et al. because (a) Magnani et al. teach allogeneic hematopoietic cell transplantation is a promising therapeutic approach in the treatment of hematologic diseases with risks of developing graft-versus-host disease (GVHD) [p2, 004], (b) Gao et al. teach the total number of infused MAITs in the graft of gut GVHD patients was significantly lower than that of no GVHD patients and suggest the potential functional effects of infused MAIT cells on gut GVHD(p1, Results to p2, para 2; p2, Fig 1), and (c) Varelias et al. teach MAIT cells abrogate GVHD induced by allogeneic stem cell transplantation and further suggest any effect on survival was due to the absence of MAIT cells alone (p1923, col 1, last para to col 2, last line 4-5; Fig 1 A and B). The combination would have reasonable expectation of success because all references teach graft-versus-host disease (GVHD) as a complication resulting from allogeneic hematopoietic cell transplantation.
With respect to claim 2, Magnani et al. teach, a patient may avoid reintroducing diseased cells from his own autologous donation into his system by using allogenic cells, reading allogeneic hematopoietic cell transplantation [p2, 004].
With respect to claims 3-4 and 8, Magnani et al. teach hematopoietic cell transplantation is a promising therapeutic approach in the treatment of hematologic diseases, disorders, or conditions (e.g., thalassemias, sickle cell disease, leukemias, lymphomas, myelomas) as well as in rescue from chemotherapy and high-dose radiation such as cancer therapy [p2, 004].
With respect to claim 5, Magnani et al. teach the transplanted patients under chemotherapy or high-dose radiation [p12, 037; p57, claim 37], reading on undergone a cytoablative therapy.
With respect to claim 6, Varelias et al. teach MAIT cells found in relatively high frequencies in the blood, liver, and GI tract (p1921, col 1, last para to col 2, line 1-2); thus one of ordinary skill in the art would have found it obvious to isolate MAIT cells from blood samples. Furthermore, Varelias et al. teach MAIT cell expansion ex vivo (p1934, col 1, para 5), reading on prepared from cell culture.
With respect to claim 7, Varelias et al. teach functional MAIT cells are activated and expressing IL-17 (p1928, col 1, last para to col 2, para 1). Varelias et al. teach MAIT cell activation requires presentation of riboflavin-based precursors captured by the MHC class I–related molecule MR1. In addition, MAIT cells can also be activated in an antigen-independent manner by IL-12 and IL-18. The end result of MAIT cell activation is to limit microbial colonization and disease by potential pathogens (p1931, col 2, para 2). Varelias et al. further teach IL-17 is required to maintain epithelial cell barrier function, and perturbation of IL-17 in this context can lead to enhanced inflammation and GI damage. It is thus likely that the protection from GVHD in the GI tract by MAIT cells reflects their role in maintaining mucosal integrity and that the enhanced donor T cell responses (p1932, col 1, para 1). Because (i) Varelias et al. teach MAIT cell expansion ex vivo (p1934, col 1, para 5) and (ii0 functional MAIT cells are beneficially activated to express IL-17 (p1928, col 1, last para to col 2, para 1) to maintain epithelial cell barrier function (p1932, col 1, para 1), one of ordinary skill in the art would have found it obvious to beneficially administer activated and expanded MAIT cells to reduce the risk of developing complications of graft-versus-host disease GVHD for Magnani’s patients after allogeneic hematopoietic cell transplantation.
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 § 2146 et seq. 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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
Claims 1-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 of copending Application No. 17/414,689 (the ‘689 application) in view of Magnani et al. (WO 2017/079,215 A1) in view of Gao et al. (Blood. (2019) 134 (Supplement 1): 2001) and Varelias et al. (J Clin Invest. 2018;128(5):1919-1936, cited in IDS 6/9/2023).
Claim 1 of the ‘689 application disclosed a method of administering mucosa
associated invariant T (MAIT) cells to a subject with cancer in need.
Claim 2 of the ‘689 application disclosed the cancer is a hematologic malignancy.
Claims 1-2 of the ‘689 application do not teach administering a therapeutically effective amount of a population of MAIT cells to control Graft Versus Host Disease (GVHD) for hematologic malignancy therapy in the patient after transplantation.
The relevancy of Magnani et al. in view of Gao et al. and Varelias et al. as applied to claims 1-8 above not repeated here.
Because Magnani et al. in view of Gao et al. and Varelias et al. teach beneficial administration of an effective amount of MAIT cells to control Graft Versus Host Disease (GVHD) in the patient after transplantation for hematologic malignancy therapy, one of ordinary skill in the art would have found it obvious to combine an effective amount of mucosa associated invariant T (MAIT) cells taught by claims 1-2 of the ‘689 application for hematologic malignancy therapy with Magnani et al. in view of Gao et al. and Varelias et al. for the same purpose of hematologic malignancy therapy.
Thus, claims 1-2 of the ‘689 application in view of Magnani et al., Gao et al. and Varelias et al. are obvious to the instant claims 1-8
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claim is allowed.
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/J.L/Examiner, Art Unit 1658
31-December-2025
/LI N KOMATSU/ Primary Examiner, Art Unit 1658