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 .
DETAILED ACTION
Claims 1-29 are pending in the instant application and are being examined on the merit.
Objections to the Claims
Claim 18 is objected to because of the following informalities:
Regarding instant claim 18, the abbreviation for membrane-bound interleukin 15 is inconsistent, wherein instant claim 18 uses “IL15”, while it is “mbIL15” in instant claims 13 and 25. Appropriate correction is required.
Objections to the Drawings
The drawings are objected to because Figures 28B and 28C have overlapping text boxes wherein the NKG2A text is directly over background label within the graph on page 44 of the Drawings. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections – 35 USC § 112(b)
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 1-2, 4-5, 7-8, and 10-29 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.
Regarding instant claims 1, 18, and 25, the meets and bounds of a CDR-H1, CDRH2, and CDRH3 contained within the VH and a CDR-L1, CDRH2, and CDRL3 contained within the VL of the claimed sequence identifiers are indefinite to: A) what applicant intends as the scope of the CDRs, wherein it’s unclear what Applicant intends as the CDR because without the specific SEQ ID it’s unclear what applicant is intending to claim; and B) a person having ordinary skill in the art for the scope of the CDRs. For A) and B) separate CDR definitions are known to the prior art such as Kabat, Chothia, and IMGT which have separate definitions of a CDR for a VH and VL, but recitation of the CDR sequences are required to provide exactly what Applicant has determined are the CDR sequences.
MPEP 2171 states Two separate requirements are set forth in 35 U.S.C. 112(b)
and pre-AIA 35 U.S.C. 112, second paragraph, namely that:
(A) the claims must set forth the subject matter that the inventor or a joint inventor
regards as the invention; and
(B) the claims must particularly point out and distinctly define the metes and bounds of
the subject matter to be protected by the patent grant.
The first requirement is a subjective one because it is dependent on what the
inventor or a joint inventor for a patent regards as his or her invention. Note that
although pre-AIA 35 U.S.C. 112, second paragraph, uses the phrase "which applicant
regards as his invention," pre-AIA 37 CFR 1.41(a) provides that a patent is applied for
in the name or names of the actual inventor or inventors.
The second requirement is an objective one because it is not dependent on the views of the inventor or any particular individual, but is evaluated in the context of whether the claim is definite — i.e., whether the scope of the claim is clear to a hypothetical person possessing the ordinary level of skill in the pertinent art.
Thus, the metes and bounds of the claims are indefinite. Recitation of the CDR sequence is required. Instant claims 2, 4-5, 7-8, 10-17, 19-24, and 26-29 further contain the indefinite subject matter without narrowing the claims outside of the rejection.
Regarding instant claim 10, the metes and bounds of the claim are unclear because the claim states “wherein anti-CD70 binding is a single-chain variable fragment (scFv)”. It is unclear if the CAR is binding a scFv or is a scFv. Recommended claim language is to exchange the text above with ---wherein the anti-CD70 binding domain is a single-chain variable fragment (scFv)--- .
Claim Rejections – 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-16 and 18-23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Instant claims 1 and 18 claim methods of treating a CD70-expressing cancer in a subject comprising administering to the subject a population of genetically engineered immune cells expressing an anti-CD70 chimeric antigen receptor CAR, but the immune cells are not required to be NK cells, T cells, or macrophages. The instant disclosure does not provide written description of cancer treatment with other types of immune cells. Instant claims 2-16 and 17-23 are dependent on instant claims 1 and 18 without narrowing the claim to a NK cell or T cell as the immune cell.
Scope of the claimed genus
Instant claims 1 and 18 claim methods of treating a CD70-expressing cancer in a subject comprising administering to the subject a population of genetically engineered immune cells expressing an anti-CD70 chimeric antigen receptor CAR, but the cells are not required to be immune cells. Instant claims 2-16 and 18-23 are dependent on instant claims 1 and 18 without narrowing the claim to a NK cell or T cell as the immune cell.
Summary of Species disclosed in the original specification
The instant specification that CAR constructs were expressed in: 1) NK cells (Fig. 61D) and T cells (Fig 50E-F) . In a cytotoxicity assay, the tested NK constructs NK77.11, NK77.16, NK77.17, NK77.58, and NK77.71 in donor 512 NK cells all exhibited greater cytotoxicity at E:T ratios of either 1:2 or 1:4 against 786-O cells (Figures 61K-61L) or ACHN cells (Figures 61M-61N) relative to NK71 control and negative control (page 167, [00369]). The cytotoxicity of anti-CD70 CAR expressing NK cells against tumor cells with gene editing was further shown in Fig. 44A-C, 49H-49I, 55A-55M, 56A-56J. Figure 31A shows CAR expression levels an anti-CD70 CAR (NK71) on NK cells treated with CD70 gRNA, CD70 and CISH gRNAs, CD70 and NKG2A gRNAs, CD70 and TGFBR2 gRNAs.
The instant specification does not test CAR expression in any other immune cells and whether they functionally can be used to treat cancer.
State of the Relevant Art
The prior art has taught CAR expression in immune cells as effective in cancer treatment, but not all immune cells have been shown to be effective at treating cancer cells when expressing a CAR. Leslie M et al. (Science 9/13/2018 doi: 10.1126/science.aav4154) taught CAR expression in T cells (page 2, paragraph 2) and NK cells (page 2, paragraph 5), and macrophages (page 3, paragraph 1-2) as effective in cancer treatment. The prior art has shown CD70-specific CAR-T cells can effectively recognize and kill CD70-positive HNSCC cells efficiently, but not CD70-negative cancer cells (Park YP et al. (Oral Oncology 2018 78 145-150) abstract).
Further regarding CAR expression in immune cells generally, genetic engineering to reduce expression of NKG2A protein in immune cells is not possible. The prior art has shown that NKG2A is an ITIM-bearing receptor expressed on both T and NK cells. (Andre P et al. (Cell 2018 175, 1731–1743) page 1732, left column, first paragraph). The prior art has not described NKG2A expression in macrophages.
The prior art does not show CAR expression in all immune cells is effective at treating cancer.
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 1-2, 4-5, and 14-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 111, 114, 118-119, 121-137 of copending Application No. 18/179,201. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding instant claims 1-2, 4-5, and 14-16, ‘201 taught a method of treating a CD70-expressing cancer in a subject comprising administering a population of NK cells (instant claim 17 ) engineered to express a CAR comprising a binding domain that targets CD70, a transmembrane domain, and a cytotoxic signaling complex, wherein the binding domain that targets CD70 comprises a scFv (instant claim 10) comprising SEQ ID NO:52, which comprises a VH sequences of NYAIS; GIIPIFGTANYAQKFQG; and DHSAGTHHDAFDI which would be a Kabat defined CDR sequence identical to instant SEQ ID NO:956 and a VL sequences of RASQSIGNWLA; DASDLET; and QQSYTTPWT which would be a Kabat defined CDR sequence identical to instant SEQ ID NO:1030 (instant claims 1 and 4), wherein the VH and VL region of the scFv have at least a 90% sequence identity to a VH of instant SEQ ID NO:956 and a VL of instant SEQ ID NO:1030 (instant claims 2 and 5 ) wherein CD70 (instant claim 14 ), CIS (instant claim 15 ), and CBLB (instant claim 16 ) are genomically disrupted, which would be genetically editing to reduce the expression of the protein of the gene, in copending claims 119 and 111.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-2, 4-5, 11-12, and 14-17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 111, 114, 118-119, 121-137 of copending Application No. 18/179,201.
The claims of copending ‘201 teach the limitations of claims 1-2, 4-5, 14-16 for the reasons set forth above.
The claims of copending ‘201 did not teach a single embodiment of a method of treating cancer with NK CAR cells wherein the cells comprised a CD8alpha transmembrane domain, and a cytotoxic signaling complex comprising OX-40 and CD3zeta, but this is obvious in view of the claims of ‘201.
Regarding instant claims 11-12, ‘201 taught a population of NK cells engineered to express a CAR comprising a binding domain that targets CD70, a transmembrane domain, and a cytotoxic signaling complex, wherein the binding domain that targets CD70 comprises a scFv comprising SEQ ID NO:52, wherein CD70, CIS, and CBLB are genomically disrupted in copending claim 111 and further taught the NK CAR cells as comprising a CD8alpha transmembrane domain in copending claim 124, and a cytotoxic signaling complex comprising OX-40 and CD3zeta in copending claim 125. The claims of ‘201 further taught a population of NK cells engineered to express a CAR comprising a binding domain that targets CD70, a transmembrane domain, and a cytotoxic signaling complex, wherein the binding domain that targets CD70 comprises a scFv comprising SEQ ID NO:51, 52, or 53 wherein CD70, CIS, and CBLB are genomically disrupted in copending claims 111, 114, 118, and 121-127, and a method for generating CAR cells in immune cells in copending claims 129-137.
Regarding instant claims 11-12, it would have been obvious for a person having ordinary skill in the art to take the method of the above copending claims 119 and 111 for a method of treating a CD70-expressing cancer in a subject comprising administering a population of NK cells engineered to express a CAR comprising a binding domain that targets CD70, a transmembrane domain, and a cytotoxic signaling complex, wherein the binding domain that targets CD70 comprises a scFv comprising SEQ ID NO:52, wherein CD70, CIS, and CBLB are genomically disrupted – and:
include in the CAR a CD8alpha transmembrane domain as described in copending claim 124, and a cytotoxic signaling complex comprising OX-40 and CD3zeta as described in copending claim 125.
This is obvious with a reasonable expectation of success because: 1) ‘201 described the NK CAR cells as further comprising a CD8alpha transmembrane domain in copending claim 124, and a cytotoxic signaling complex comprising OX-40 and CD3zeta in copending claim 125. Further, NK CAR cells would require a transmembrane domain and cytotoxic signaling complex to functionally kill cancer cells. Thus, these regions would be expected to be functional wherein the scFv targets CD70 expressing cancer cells and the transmembrane domain and cytotoxic signaling complex to functionally kill cancer cells.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 1-29 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN J SKOKO III whose telephone number is (571)272-1107. The examiner can normally be reached M-F 8:30 - 5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Z Wu can be reached at (571)272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/J.J.S./Examiner, Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643
Prosecution Insights