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 .
Claims 1-14 are pending and have been considered on the merits.
Priority
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. 16/625678, filed on 7/2/2018. The earliest filing date of the instant application has been determined as the filing date of DKPA201770542, which is 6/30/2017.
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 1-14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being 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 1 discloses “A set” in line 1 and “a first set” in line 2 and “a second set” in step (b). It is not clear what the term “set” is intended to point out. The claimed product is disclosed as a “set”, e.g. collection. While the “set” in line 1 appears to refer to the component of (a) and (b), it is not clear what the “first set” and “second set” is referring to. As the term “set” is interpreted as collection of components, it is vague how the cells from a single donor would be a set. Does the “first set” and “second set” require additional element or items in the set other than the engineered allogeneic T cells? Clarification is required.
Applicant is advised to amend the limitation to, for example, “a first dose of engineered allogeneic T cells” and “a second dose of engineered …” instead.
Similarly, the “third set”, “fourth set”, and “fifth set” in claims 2-4 would be amended accordingly. i.e. “a third dose”, “a fourth dose”, and “a fifth dose”.
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) 1-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over Torikai et al. (2016, Molecular Therapy) in view of Cooper (2010, Blood)
The instant claims are interpreted as a collection of an individual composition of engineered allogeneic T cells from a single donor from at least two different donors, wherein the T cells have been modified to express CAR and inactivated the endogenous TCR gene.
Torikai et al. teach “off-the-shelf” donor-derived biobanks comprising CAR-T cells pre-prepared, validated and cryopreserved in advance from one or more healthy unrelated donors, i.e. OTS CAR+T-Cell Therapy (p.1179). Torikai et al. teach one or more biobanks of the OTS T-cell products could then be administered into multiple recipients (p.1179). The biobank of Torikai et al. would comprise multiple population of CAR-T cells from different donors, and thus, the whole set of the CAR-T cells from different individual donors would read on the claimed set of doses of CAR-T cells.
Regarding the engineered allogeneic T cells containing a CAR and the endogenous TCR gene being inactivated, Torikai et al. teach that the OTS CAR+T cells would be engineered to eliminate the endogenous TCR to avoid GvHD (p.1180, Table 3).
Regarding the second, third, fourth or fifth set of engineered allogeneic T cells from different donors have no common HLA alleles, as the biobank of Torikai et al. comprises CAR-T cells from different donors, it would have been obvious to a person skilled in the art that there would be different populations of CAR-T cells from different donor that would have no common HLA alleles.
Regarding the limitation of claims 5-7 directed to the first set of engineered allogeneic T cells matching at least 6, 8 or 9 of HLA markers of patient, as the instant claims are directed to a product which does not require any HLA types of the patients, the limitations do not provide any structure to the claimed product. Nevertheless, as the biobanks comprising one or more CAR-T cells from one or more healthy donors, it would have been obvious to a person skilled in the art that the bank would have the CAR-T cells with matching HLA as claimed with a reasonable expectation of success, particularly when the numbers of cell population or the number of donors for the biobank is sufficiently large enough. Furthermore, Cooper teaches that pairing a patient with cryopreserved T cells (in the bank) is based upon matching the recipient (patient) with preference given to the cryopreserved product having the greatest number of shared MHC loci, and in addition to this typing, a bank’s in vitro data should be queried so that priority is given to T-cell lines that indeed recognize the desired antigen through a restricting MHC molecule that is shared by the recipient (p.4742, 2nd col.).
Regarding claim 8 directed to the dose ranging from the claimed amount the cells per body weight of the patient, this limitation requires the body weight of the patient. As the claimed product does not require any step of administering to any patient, the dose determined based on the body weight of the patient would not be considered limiting. Nevertheless, Torikai et al. teach that the dose of CAR-T cells being 3x108 per patient (p.1182, 2nd col.), and this would meet the claimed dose considering the body weight of the patient being about 50-100 kg (i.e. 3x108 per 50-100kg would be 3x106 to 1.5x107 cells/kg). This is consistent with the teaching of Cooper such that intravenous dose of 106/kg/infusion to 2x106/kg/infusion (p.4741, 3rd col.).
Regarding claims 9-10, the CAR-T cells of Torikai et al. in the biobanks would meet the limitation.
Regarding claim 11 directed to the CAR of the first set and the second set are directed to the same antigen or claim 13 directed to the CAR of the first set and the second set directed against different antigens, while Torikai et al. do not particularly teach the limitation, however, one skilled in the art would recognize that the biobank of Torikai et al. would comprise not only CAR-T cells from different donors but targeting the same antigen (e.g. CD19, see p.1184 of Torikai et al.) but also the CAR-T cells targeting the different antigens because the cell banks can store various different type of CAR-T cells for the purpose of “off-the-shelf” cellular therapies.
Regarding claims 12 and 14 directed to the antigen being CD123, CD19 or CD22, Torikai et al. teach CD19 specific CAR T cells for leukemia (p.1179-1180).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
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 1-14 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 10,357,515 in view of Torikai et al. (2012, Blood; IDS ref.). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the ‘515 patent disclose a method of generating a batch of T-cells from individual human donors with the gene encoding TCR component being disrupted, and the T-cells express CAR. The claims of the ‘515 patent disclose that the donors express different HLA types. Thus, the claims of the ‘515 patent directed to the batch comprising mixture of multiple doses of T cells from multiple donors would render the set or kit comprising several doses of CAR-T cells with the endogenous TCR gene being inactivated from different donors of the instant application obvious.
As discussed above, the HLA typing of the CAR-T cells being different from the patient, this limitation does not provide specific structure to the claimed product as the patient is not a part of the claimed product. Similarly, the amount/dose of the cells being administered per body weight of the patient would not determine the patentability of the claimed product as the body weight of patient is not a part of the claimed product.
Regarding the CAR being directed to the same or different antigens, claim 11 of the ‘515 patent discloses at least one CAR, and it would have been obvious to a person skilled in the art that the batch of the ‘515 patent would comprise CAR-T cells directed to the same or different CAR targeting different antigens. Regarding the antigen being CD123, CD19 or CD22, it is well known in the art that CD19 is an antigen targeted by CAR for cancer treatment. As claim 19 of the ‘515 patent discloses a method of treating cancer, it would have been obvious to a person skilled in the art to engineer the CAR to target CD19 for treating leukemia according to Torikai et al. (see entire document).
Thus, the claims of the ‘515 patent in view of the cited reference render the claims of the instant application obvious.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TAEYOON KIM whose telephone number is (571)272-9041. The examiner can normally be reached 9-5 EST Monday-Friday.
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/TAEYOON KIM/Primary Examiner, Art Unit 1631
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