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 .
1. The Election filed October 10, 2025, in response to the Office Action of June 10, 2025, is acknowledged and has been entered. Applicants elected without traverse the species of:
A. (i) CD28 polypeptide has reduced recruitment of a p85 subunit of a PISK as compared to a CD28 molecule comprising native YMNM motif (Claim 2a);
B. Mutated YMNM motif YSNV SEQ ID NO:23 (claims 5-7), SEQ ID NO:64 (claim 70);
B1. CAR SEQ ID NO:57 (claim 32) encoded by SEQ ID NO:58 (claim 71); and
C. CD19 antigen (claim 28).
The species of motif YKNI (SEQ ID NO:26) and the CAR encoding the motif (SEQ ID NO:55) are rejoined for examination (claims 5, 6, 30, 32).
Claims 1, 2, 4-7, 9-12, 18-25, 28, 30, 32, 45, 47, 49-51, 54, 55, 58, 59, 62, 64, 66, 68, 70, and 71 are pending. Claims 70 and 71 are new. Claims 9-12, 18-24 are withdrawn as being drawn to non-elected species. Claims 1, 2, 4-8, 25, 28, 30, 32, 45, 47, 49-51, 54, 55, 58, 59, 62, 64, 66, 68, 70, and 71 are currently under prosecution as drawn to the elected species.
Specification/ Drawings
2. The specification and drawings are objected to. This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.831. Specifically, there is no SEQ ID NO identified with the sequence disclosed in Figure 1 (YMNM) or with the 4 amino acid sequences referenced throughout the specification. 37 CFR 1.831 (a)-(c) requires that a reference to a particular sequence identifier (i.e., SEQ ID NO:#) be made in the specification and drawings wherever a reference is made to that sequence:
(a) Patent applications disclosing nucleotide and/or amino acid sequences by enumeration of their residues, as defined in paragraph (b) of this section, must contain, as a separate part of the disclosure, a computer readable Sequence Listing in XML format (a "Sequence Listing XML"). Disclosed nucleotide or amino acid sequences that do not meet the definition in paragraph (b) of this section must not be included in the "Sequence Listing XML." The "Sequence Listing XML" contains the information of the nucleotide and/or amino acid sequences disclosed in the patent application using the symbols and format in accordance with the requirements of §§ 1.832 through 1.834.
(b) Nucleotide and/or amino acid sequences, as used in this section and §§ 1.832 through 1.835, encompass:
(1) An unbranched sequence or linear region of a branched sequence containing 4 or more specifically defined amino acids, wherein the amino acids form a single peptide backbone; …
(c) Where the description or claims of a patent application discuss a sequence that is set forth in the "Sequence Listing XML" in accordance with paragraph (a) of this section, reference must be made to the sequence by use of the sequence identifier, preceded by "SEQ ID NO:" or the like in the text of the description or claims, even if the sequence is also embedded in the text of the description or claims of the patent application. Where a sequence is presented in a drawing, reference must be made to the sequence by use of the sequence identifier (§ 1.832(a) ), either in the drawing or in the Brief Description of the Drawings, where the correlation between multiple sequences in the drawing and their sequence identifiers (§ 1.832(a) ) in the Brief Description is clear.
With regard to Figure 1: Applicants may obviate the objection of drawings by amending the Brief Description of the Drawings or the Drawings to identify the amino acid sequence(s).
If Applicants choose to amend the Drawings: 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.” 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.
Claim Objections
3. Claim 71 is free of the art but is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. The instantly claimed CD19 CAR comprising YSNV motif (SEQ ID NO:57) encoded by nucleic acid SEQ ID NO:58 appears to be novel.
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.
4. Claim 28 is 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 28 is indefinite in the use of the expression in parenthesis “(also known as KK-LC-1)” in that it is not clear whether this recitation is intended to be part of the claim or not.
Examiner Suggestion: Amend claim 28 to recite: “…CT83 (KK-LC-1)…” to indicate the alternative acronym and eliminate the phrase.
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.
5. Claims 54, 55, and 58 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of reducing tumor burden in a subject, treating a neoplasm or a tumor, and/or lengthening survival of a subject having a neoplasm or a tumor, the method comprising administering to the subject the cell of claim 45, does not reasonably provide enablement for a method of preventing a neoplasm or a tumor. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The factors to be considered in determining whether undue experimentation is required are summarized In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir, 1988). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation.' " (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (1) the quantity of experimentation necessary, (2) the amount or direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art, and (8) the breadth of the claims.
The claims as currently constituted encompass methods of preventing cancer.
The instant specification does not demonstrate that the claimed CAR-expressing immune cells predictably prevent cancer.
A search of relevant art does not support that CAR T cells prevent cancer. For example, WO 2018/140725, Posey et al, cited below, demonstrates that CAR T cells comprising a mutated CD28 YMNM motif treated established cancer xenografts but does not demonstrate prevention of cancer (Examples).
One cannot extrapolate the disclosure of the specification to the scope of the claims because the specification lacks the critical steps necessary in presenting some type of predictable response in a population of hosts deemed necessary to prevent cancer. Reasonable guidance with respect to preventing any cancer relies on quantitative analysis from defined populations which have been successfully pre-screened and are predisposed to particular types of cancer or have had cancer. The essential element towards the validation of a preventive therapeutic is the ability to test the drug on subjects monitored in advance of clinical cancer and Iink those results with subsequent histological confirmation of the presence or absence of disease. This irrefutable link between antecedent drug and subsequent knowledge of the prevention of the disease is the essence of a valid preventive agent. All of this underscores the criticality of providing workable examples which are not disclosed in the specification. A high quantity of experimentation would be required to determine if and what cancers the claimed CAR-expressing cell could prevent.
Reasonable correlation must exist between the scope of the claims and scope of enablement set forth, and it cannot be reasonably predicted that the claimed immune cell comprising the claimed CAR will predictably function to prevent cancer as claimed.
Therefore, in view of the state of the art, the quantity of experimentation necessary, the breadth of the claims, lack of guidance in the specification, and the absence of working examples, it would require undue experimentation for one skilled in the art to practice the invention as broadly claimed.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
6. Claim interpretation: Claim 1 recites that the at least one co-stimulatory signaling domain of the CAR comprises “a CD28 polypeptide comprising a mutated YMNM motif”. The instant specification does not provide a limiting definition of what “a CD28 polypeptide” is, therefore the term is reasonably interpreted to comprise the mutated CD28 YMNM motif itself (i.e., YSNV or YKNI).
7. Claim(s) 1, 2, 4-7, 25, 28, 30, 45, 47, 49-51, 54, 55, 62, 64, 66, 68, and 70 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US Patent Application Publication 2018/0044399, Rajpal et al, published February 15, 2018.
Rajpal teaches there is a safety issue pertaining to on-target off-tissue activity of CAR T-cells, and there is growing emphasis in creating logic gates to modulate T-cell signaling to solve this problem ([3]). Rajpal suggests a solution:
[0004] One such approach involves using a NOT gate, wherein the T-cell expresses two or more CARs on its cell surface. CARs that provide positive T-cell signals (P-CARs) bind to tumor antigens to enable T-cell activation and/or proliferation and/or cytokine secretion, and/or cytotoxicity mediated by CD3zeta or other immunoreceptor tyrosine-based activation motif (ITAM) containing motifs; while CARs that provide a negative T-cell signal (N-CARs) bind to the off-tissue antigens and attenuate or abrogate the positive signals.
[0005] Therefore under the on-tissue (on-tumor) scenario the T-cell only receives the P-CAR signal and subsequent activation and cytotoxicity and in the off-tissue (off-tumor) scenario the T-cell receives both the P-CAR and N-CAR signals, whereby the latter attenuates or terminates downstream signaling leading to impaired or no activation and cytotoxicity.
[0006] Therefore, there is a need for negative or inhibitory CAR (N-CAR) that can be used to generate a negative signal suitable to prevent off target activation of P-CAR T-cells (T-cells comprising a P-CAR). It would be an additional benefit if such negative signal is short-termed, reversible and sufficient to attenuate or prevent on-target off-tissue activity of CAR T-cells comprising such N-CAR.
For the inhibitory chimeric antigen receptor (N-CAR) construction, Rajpal teaches the N-CAR comprises (claim 1):
an extracellular domain comprising an antigen binding domain,
a transmembrane domain
an intracellular domain;
wherein the antigen binding domain binds CD34 antigen ([343]; [661]; [640]; claim 13);
wherein the intracellular domain comprises an immunoreceptor tyrosine-based inhibitory motif (ITIM) SEQ ID NO:1887 (VKYSNV) ([286-287]; Examples 1 & 2, [384-386]) that is a mutated CD28 polypeptide YMNM motif consisting of YSNV.
Rajpal further teaches a nucleic acid encoding the N-CAR, vector comprising the nucleic acid encoding the N-CAR, and host cell expressing the nucleic acid ([344-347]; [689-690]; claims 24-25); an immune cell expressing the N-CAR, wherein the immune cell is a T cell ([346-347]; [354-369]; [376-377]; [656-660]; claims 18-20); wherein the immune cell is a cytotoxic T lymphocyte (CTL) or T regulatory (Treg) cell ([672]); a method for producing the immune cell expressing the N-CAR comprising introducing into the cell a nucleic acid molecule encoding the N-CAR (claim 22; [346]; [369]; [674]); a pharmaceutical composition comprising the immune cell ([53]); and methods of treating cancer comprising administering the immune cell to a patient (claims 21 and 23; [25]; [53]; [671]; [675-677]) in order to eliminate or reduce cancer ([53]); wherein the immune cell kills target cells ([686]); wherein the cancer is a leukemia or lymphoma ([25]).
With regard to claim 68, the CAR of claim 1 is the only product recited in claim 68 to identify the kit, and Rajpal teaches the CAR of claim 1, therefore anticipates the claimed kit.
With regard to claim 2, the N-CAR of Rajpal comprises the same intracellular domain YSNV sequence instantly claimed, therefore inherently functions to reduce recruitment of p85 subunit of PI3K as compared to an intracellular domain comprising the YMNM motif.
Instant SEQ ID NO:23 aligned with SEQ ID NO:1887 of Rajpal:
RESULT 5
US-15-525-906A-1887
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
Sequence 1887, US/15525906A
Publication No. US20180044399A1
GENERAL INFORMATION
APPLICANT: Rinat Neuroscience Corp.
APPLICANT: Cellectis
TITLE OF INVENTION: INHIBITORY CHIMERIC ANTIGEN RECEPTORS
FILE REFERENCE: PC72174A
CURRENT APPLICATION NUMBER: US/15/525,906A
CURRENT FILING DATE: 2017-10-10
PRIOR APPLICATION NUMBER: PCT/IB2015/058650
PRIOR FILING DATE: 2015-11-09
PRIOR APPLICATION NUMBER: US 62/078,927
PRIOR FILING DATE: 2014-11-12
PRIOR APPLICATION NUMBER: US 62/081,960
PRIOR FILING DATE: 2014-11-19
NUMBER OF SEQ ID NOS: 2029
SEQ ID NO 1887
LENGTH: 6
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic Construct
Query Match 100.0%; Score 21; Length 6;
Best Local Similarity 100.0%;
Matches 4; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 YSNV 4
||||
Db 3 YSNV 6
8. Claim(s) 1, 2, 25, 28, 45, 47, 49-51, 54, 55, 58, 59, 62, 64, 66, and 68 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2018/140725, Posey et al.
Posey teaches a CAR comprising an:
extracellular domain binding to CD19 tumor antigen (p. 7, 10, 20, 30, 68, 131-153; Table 3 and 4; p. 265);
transmembrane domain; and
intracellular signaling domain comprising CD28 costimulatory domain that is mutated from YMNM to YMFM (SEQ ID NO:1937) as comprised in CD28 costimulatory domain SEQ ID NO:2; or mutated to FMNM (SEQ ID NO:1948) as comprised in CD28 costimulatory domain SEQ ID NO:3; and functions to reduce recruitment of a p85 subunit of PI3K as compared to native YMNM motif (p. 2-3; 6-7; 11-12; 15; 19; Table 1; p. 116, Examples 1-7).
Posey teaches and demonstrates that the intracellular CD28 costimulatory mutated YMNM regions result in a CAR that reduces the interaction with PI3K, wherein YMFM ablates interaction with PI3K and FMFM removes interaction with both PI3K and Grb2 (Example 2).
Posey further teaches nucleic acid encoding the CAR, vectors comprising the nucleic acid, host cells comprising the nucleic acid (p. 13-15, 228-239); methods of making CAR-expressing cells by introducing in the cells a nucleic acid molecule encoding the CAR (p. 33-37, 70-71); immune effector cells, including T cells, Treg, and NK cells, expressing the CAR (p. 1, 24-26, 35-37, 237-239; Examples 1-3); pharmaceutical composition comprising the cell expressing CAR (p. 264, 342-343); methods of treating cancer in a subject comprising administering to the subject an immune effector cell expressing the CAR, wherein the cancer is B-cell leukemia, acute lymphoid leukemia (ALL), chronic lymphocytic leukemia (CLL), B cell lymphoma, non-Hodgkin’s lymphoma, or AML, and wherein tumor growth is inhibited (p. 28-32, 264-289).
Posey successfully treats tumors in vivo by administering T cells expressing the CAR comprising the mutated YMFM motif, and teaches all animals treated with the mutant CAR T cell were tumor-free by the end of the experiment (Example 4).
With regard to claim 68, the CAR of claim 1 is the only product recited in claim 68 to identify the kit, and Posey teaches the CAR of claim 1, therefore anticipates the claimed kit.
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.
9. Claim(s) 1, 2, 4-6, 25, 28, 45, 47, 49-51, 54, 55, 58, 59, 62, 64, 66, and 68 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/140725, Posey et al; in view of Posey 2017 (Molecular Therapy, May 2017, 25:154, abstract 330, IDS); and Kessels et al (PNAS, 2002, 99:8524-8529).
Posey teaches a CAR binding to CD19 and comprising an intracellular CD28 costimulatory domain comprising a mutant YMNM motif that functions to reduce binding to PI3K and maintains Grb2 binding, and additional limitations as set forth above.
Posey does not teach the mutant YMNM motif comprises a motif that is of formula YxNx where x is not a methionine; and a motif that consists of YKNI.
Posey 2017 teaches that CAR T cells co-stimulated by CD28 are not detectable in patients after 90 days. Mutating the CD28 co-stimulatory domain to decrease PI3K activity delays signaling responses, reducing calcium influx, similar to 4-1BB activity that is demonstrated to exert a long-lived persistence if CAR T cells in patients. Posey 2017 teach that mutating the CD28 costimulatory domain in CAR T cells allowed for improved tumor rejection and cell persistence. Posey 2017 suggests retooling CD28-costimulated CAR T cells to provide a more effective and long-lived phenotype in patients through mutation of CD28 signaling motifs.
Kessels teaches the YMNM sequence derived from the CD28 molecule is a T cell-specific tyrosine kinase receptor, containing both the Grb2 SH2 binding motif pYXNX and the phosphatidylinositol 3-kinase (PI3-kinase, PI3K) SH2 binding motif pYMXM comprising methionines. In line with these findings, this CD28 binding site has been shown to bind both Grb2 and PI3-kinase upon tyrosine phosphorylation (p. 8528, col. 1). Kessels mutated the CD28 costimulatory domain YMNM motif to YKNI (named “CD28KNI”) eliminating the methionines, and determined it lost the ability to bind PI3Kp85-C SH2, but remain capable of recruiting Grb2 (Figure 7; p. 8528, col. 2). Kessels teaches identifying Grb2 binding domains through their defined screening process in order to produce more ligand binding domains highly specific for Grb2, to be applied for in vivo ligand selection (abstract). The motif YKNI is identical to instant SEQ ID NO:26.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to substitute the mutant CD28 YMNM motif of Posey for the functionally equivalent mutant CD28 YKNI motif of Kessels. One would have been motivated to and have a reasonable expectation of success to because: (1) Posey, Posey 2017, and Kessels recognize that the T cell wild type CD28 YMNM motif functions to bind both PI3K and Grb2; (2) Posey teaches producing and expressing a mutated CD28 YMNM motif in their CAR intracellular domain in order to produce CAR T cells with reduced PI3K binding and signaling while maintaining Grb2 binding; (3) Posey 2017 teaches the advantage of mutating the CD28 signaling motif to reduce PI3K signaling, improve tumor rejection, and improve CAR T cell persistence; (4) Kessels teaches identifying mutated motifs that are highly specific to Grb2 for in vivo application of ligand binding; and (4) Kessels demonstrates mutated CD28 YKNI motif functions to specifically bind Grb2 but not PI3K.
Given: (1) the T cell receptor CD28 mutated motifs of Posey and Kessels perform the same function of inhibiting binding to PI3K while maintaining binding to Grb2, (2) one of ordinary skill in the art would have recognized the interchangeability of the motifs given the cited references teach the motifs are mutated CD28 YMNM motif from T cells, and teach the advantage of mutated CD28 signaling motifs in tumor treatment with CAR T cells; and (3) there are insubstantial differences between the mutant CD28 motifs of Posey and Kessels, one of ordinary skill in the art could have substituted one known functionally equivalent CD28 motif of Kessels for the known CD28 motif of Posey, and produced a functional CAR with a reasonable expectation of success.
10. Claim(s) 32 is rejected under 35 U.S.C. 103 as being unpatentable over WO 2018/140725, Posey et al; Posey 2017 (Molecular Therapy, May 2017, 25:154, abstract 330, IDS); and Kessels et al (PNAS, 2002, 99:8524-8529) as applied to claims 1, 2, 4-6, 25, 28, 45, 47, 49-51, 54, 55, 58, 59, 62, 64, 66, and 68 above, and further in view of US Patent Application Publication 2018/0044399, Rajpal et al, published February 15, 2018.
Posey, Posey 2017, and Kessels (the combined references) teach a T cell expressing a CAR comprising an antigen binding domain to CD19, a transmembrane domain, and an intracellular domain comprising a CD28 costimulatory signaling domain that is a mutated YMNM motif “YKNI” binding to Grb2 and not to PI3K, as set forth above. As stated above, Posey teaches several exemplary CD19 antigen binding sequences known in the art to utilize in the CAR construction (131-153; Table 3 and 4).
The combined references do not teach the CD19 CAR comprises instant SEQ ID NO:55 that harbors the YKNI motif.
Rajpal teaches and exemplifies producing a P-CAR (positive signaling CAR) comprising an extracellular domain that binds to CD19, a transmembrane domain, and intracellular CD28 costimulatory signaling domain represented by SEQ ID NO:2020 (P-CAR2; Table 9; [348-354]; Example 3). SEQ ID NO:2020 is 100% identical to instant SEQ ID NO:55 except that SEQ ID NO:2020 comprises the wild-type YMNM motif (see sequence alignment below). Rajpal teaches P-CAR2 (SEQ ID NO:2020) CD19 binding region was produced from known anti-CD19 antibody sequences of antibody SJ25C1 (citing US2013063097), and comprises a CD28 hinge and transmembrane domain, and an intracellular domain comprising a CD28 and CD3zeta intracellular signaling domains (Example 3). Rajpal teaches expressing the P-CAR in T cells and administering the cells to treat leukemia or lymphoma, as set forth above, and as disclosed in Examples 4 and 5.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to utilize the known CD19 CAR sequence of Rajpal in making the CD19 CAR of the combined references comprising the mutant CD28 YKNI motif. One would have been motivated to and have a reasonable expectation of success to because: (1) the combined references suggest utilizing known CD19 sequences in the prior art to construct the CD19 CAR harboring the mutant CD28 YMNM domain; (2) Rajpal provides the known sequence of a CD19 CAR harboring the wild type CD28 YMNM motif and demonstrates it is successfully expressed by T cells and treats cancer. Given the disclosure of the cited prior art, is well within the level of the ordinary skill artisan to modify the known CD19 CARs sequence of Rajpal by mutating the YMNM motif to YKNI, with a reasonable expectation of success.
Instant SEQ ID NO:55 aligned with SEQ ID NO:2020 Rajpal:
RESULT 6
US-15-525-906A-2020
(NOTE: this sequence has 11 duplicates in the database searched.
See complete list at the end of this report)
Sequence 2020, US/15525906A
Publication No. US20180044399A1
GENERAL INFORMATION
APPLICANT: Rinat Neuroscience Corp.
APPLICANT: Cellectis
TITLE OF INVENTION: INHIBITORY CHIMERIC ANTIGEN RECEPTORS
FILE REFERENCE: PC72174A
CURRENT APPLICATION NUMBER: US/15/525,906A
CURRENT FILING DATE: 2017-10-10
PRIOR APPLICATION NUMBER: PCT/IB2015/058650
PRIOR FILING DATE: 2015-11-09
PRIOR APPLICATION NUMBER: US 62/078,927
PRIOR FILING DATE: 2014-11-12
PRIOR APPLICATION NUMBER: US 62/081,960
PRIOR FILING DATE: 2014-11-19
NUMBER OF SEQ ID NOS: 2029
SEQ ID NO 2020
LENGTH: 485
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic Construct
Query Match 99.6%; Score 2488; Length 485;
Best Local Similarity 99.6%;
Matches 465; Conservative 1; Mismatches 1; Indels 0; Gaps 0;
Qy 1 EVKLQQSGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIYPGDGDTNY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 19 EVKLQQSGAELVRPGSSVKISCKASGYAFSSYWMNWVKQRPGQGLEWIGQIYPGDGDTNY 78
Qy 61 NGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVYFCARKTISSVVDFYFDYWGQGTTVTV120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 79 NGKFKGQATLTADKSSSTAYMQLSGLTSEDSAVYFCARKTISSVVDFYFDYWGQGTTVTV138
Qy 121 SSGGGGSGGGGSGGGGSDIELTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQS180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 139 SSGGGGSGGGGSGGGGSDIELTQSPKFMSTSVGDRVSVTCKASQNVGTNVAWYQQKPGQS198
Qy 181 PKPLIYSATYRNSGVPDRFTGSGSGTDFTLTITNVQSKDLADYFCQQYNRYPYTSGGGTK240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 199 PKPLIYSATYRNSGVPDRFTGSGSGTDFTLTITNVQSKDLADYFCQQYNRYPYTSGGGTK258
Qy 241 LEIKRAAAIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVGGVLAC300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 259 LEIKRAAAIEVMYPPPYLDNEKSNGTIIHVKGKHLCPSPLFPGPSKPFWVLVVVGGVLAC318
Qy 301 YSLLVTVAFIIFWVRSKRSRLLHSDYKNITPRRPGPTRKHYQPYAPPRDFAAYRSRVKFS360
|||||||||||||||||||||||||| |:|||||||||||||||||||||||||||||||
Db 319 YSLLVTVAFIIFWVRSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRSRVKFS378
Qy 361 RSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKD420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 379 RSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYNELQKD438
Qy 421 KMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 467
|||||||||||||||||||||||||||||||||||||||||||||||
Db 439 KMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 485
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.
11. Claims 1, 2, 4-7, 25, 30, 45, 47, 49-51, 54, 55, 59, 62, 64, 66, 68, and 70 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 6, 8, 10, 12, 15, 23, 24, 26, 29, 30,32, 34, 35, 40, 43, 47, 52, 57, 62, and 65 of copending Application No. 18/591,403 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending application claims a CAR comprising a mutated CD28 costimulatory signaling domain YMNM motif that renders obvious the instant CAR. The copending application claims a CAR comprising an extracellular antigen-binding domain binding to antigen DLL3, a transmembrane domain, and an intracellular signaling domain that comprises a CD28 polypeptide; wherein the CD28 polypeptide comprises or consists of a mutated YMNM motif; wherein the CD28 polypeptide comprises or consists of SEQ ID NO:276 (RSKRSRLLHSDYKNITPRRPGPTRKHYQPYAPPRDFAAYRS) that comprises YKNI motif, or comprises SEQ ID NO:279 (RSKRSRLLHSDYSNVTPRRPGPTRKHYQPY APPRDFAAYRS) that comprises YSNV motif. The copending application further claims a cell expressing the CAR, wherein the cell is a T cell or NK cell, a nucleic acid encoding the CAR, a pharmaceutical composition comprising the cell, a method of treating a disease in a subject comprising administering a pharmaceutical composition comprising the cell expressing the CAR, wherein the disease is cancer.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
12. Claims 1, 2, 4-7, 25, 30, 45, 47, 49-51, 54, 55, 58, 59, 62, 64, 66, 68, and 70 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-35 of copending Application No. 19/200,121 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the copending application claims a CAR comprising a mutated CD28 costimulatory signaling domain YMNM motif that renders obvious the instant CAR. The copending application claims an immunoresponsive cell comprising a CAR comprising an extracellular antigen-binding domain binding to antigen B7-H3, a transmembrane domain, and an intracellular signaling domain that comprises a CD28 polypeptide; wherein the CD28 polypeptide comprises or consists of a mutated YMNM motif; wherein the CD28 polypeptide comprises SEQ ID NO:97 (RSKRSRLLHS DYKNITPRRP GPTRKHYQPY APPRDFAAYRS) that comprises YKNI motif; or comprises SEQ ID NO:100 (RSKRSRLLHSDYSNVTPRRPGPTRKHYQPYAPPRDFAAYRS) that comprises YSNV motif; wherein the cell is a T cell, CTL, or Treg; a pharmaceutical composition comprising the cell; a nucleic acid encoding the CAR; a vector comprising the nucleic acid, a method of producing the cell comprising introducing into the cell the nucleic acid encoding the CAR; a kit comprising the cell; and a method of treating cancer comprising administering the cell comprising the CAR, wherein the cancer is AML.
13. Conclusion: Claims 1, 2, 4-8, 25, 28, 30, 32, 45, 47, 49-51, 54, 55, 58, 59, 62, 64, 66, 68, 70 are rejected. Claim 71 is objected to.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA B GODDARD whose telephone number is (571)272-8788. The examiner can normally be reached Mon-Fri, 7am-3:30pm.
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/Laura B Goddard/Primary Examiner, Art Unit 1642