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 .
Priority
Applicant claimed the benefit of provisional application 63/395702 filed on 8/5/2022. The present claims are disclosed in the provisional application listed. The effective filing date for the present application is 8/5/2022.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (See pg. 88 [0342] line 3, pg.194 [0680] lines 9-10). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
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.
Claim 187 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. The claim recites, “the cell of claim 196,” however no claim 196 exists. The claim has been interpreted as depending from claim 186. It is suggested applicant re-write the claim to cite claim 186 to overcome this rejection.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 27 and 184-187 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Sather, et al. (WO 2020/092854 A2, cited in IDS from 1/4/2024).
In regard to claim 27, Sather discloses a bispecific CAR where the extracellular domain comprises the VH and VL region of the BCMA/GPRC5D binding domain, the VH and VL region of the GPRC5D/BCMA binding domain, a spacer, a transmembrane domain, and an intracellular signaling domain (pg. 311, example 20). Therefore, Sather anticipates claim 27.
In regard to claim 184, Sather discloses the limitations of claim 27 as discussed above. Sather further discloses a polynucleotide encoding the CAR construct (pg. 311 [0916]). Therefore, Sather anticipates claim 184.
In regard to claim 185, Sather discloses the limitations of claims 27 and 184 as discussed above. Sather further discloses a vector including the polynucleotide construct from the CAR of claim 27 (pg.311 [0917]). Therefore, Sather anticipates claim 185.
In regard to claims 186-187, Sather discloses the limitations of claim 27 as discussed above. Sather further discloses the use of a T cell for the expression of the polynucleotide construct (pg.311 [0917]). Therefore, Sather anticipates claims 186-187.
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.
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 1-2, 5, 20, 37, 40, 44, 48, 62-63, 71, 74, 77, 80, 83, 94, 102, 106, 111, 123, and 133, are rejected under 35 U.S.C. 103 as being unpatentable over Sather, et al. (WO 2020/092854 A2, cited in IDS from 1/4/2024) in view of Brinkman, et al. (MABS 2017 9:2, 182-212).
In regard to claim 1-2 and 5, Sather discloses a bispecific CAR comprising an extracellular domain comprising a heavy chain and light chain region of a GPRC5D-binding domain and a heavy and light chain region of a BCMA-binding domain, a spacer, a transmembrane domain, and an intracellular signaling domain (pg. 311, example 20). Sather does not disclose an extracellular domain comprising from amino to carboxy terminus: a variable region of GPRC5D, the VH/VL regions of BCMA, and the other variable region of GPRC5D, or where GPRC5D and BCMA are swapped.
Brinkman teaches various bispecific constructs for use in therapeutic treatment. Particularly, Brinkman teaches a bispecific construct of sandwiching the variable regions of one antigen binding domain between the variable regions of the other antigen binding domain, e.g. VH1-VL2-VH2-VL1 (See Fig. 2, box 3 and pg. 186).
It would have been obvious to a person of ordinary skill in the art to apply the bispecific antigen domain pattern taught in Brinkman to the bispecific CAR of Sather to make the disclosure of the claimed invention from claims 1-2 and 5. Sather teaches making a bispecific CAR that targets the binding domains of GPRC5D and BCMA for pharmaceutical treatment in humans. Brinkman teaches a pattern of design for bispecific antibodies that allows for compact dimerization during targeted binding that can retarget effector cells. The ability to retarget effector cells would lead to improved potency for the treatment. Additionally, the use of dimers to target cells would decrease antigen-independent signaling leading to decreased side effects from the treatment. Therefore, it would be obvious to a person of ordinary skill in the art prior to the effective filing date to combine the teachings of Sather with the teachings of Brinkman to create the bispecific CAR construct of the present claimed invention to increase the potency and decrease the side effects of pharmaceutical treatment.
In regard to claim 20, the limitations of claim 1 are disclosed as discussed above. Brinkman further discloses the VH or VL regions of any domains being joined by a linker sequence (pg. 185).
In regard to claim 37, the limitations of claim 1 are disclosed as discussed above. Sather further discloses a bispecific CAR comprising the VH and VL regions of GPRC5D binding domains comprising the amino acid sequences of SEQ ID NOs:1, 2, 3, 4, 5, and 6 (SEQ ID NO:298, 301).
In regard to claim 40, the limitations of claim 1 are disclosed as discussed above. Sather further discloses the VH and VL regions of GPRC5D binding domains comprising an amino acid sequence of at least 90% of SEQ ID NO:7 and 8, respectively (SEQ ID NO:298, 301).
In regard to claim 44, the limitations of claim 1 are disclosed as discussed above. Sather further discloses the VH and VL regions of BCMA binding domains comprising the amino acid sequences of SEQ ID NOs:9, 10, 11, 12, 13, and 14, respectively (SEQ ID NOs:298, 301).
In regard to claim 48, the limitations of claim 1 are disclosed as discussed above. Sather further discloses the VH and VL regions of BCMA binding domains comprising the amino acid sequence of at least 90% of SEQ ID NOs: 15 and 16, respectively (SEQ ID NOs:298, 301).
In regard to claims 62-63, the limitations of claim 1 are disclosed as discussed above. Sather further discloses the spacer region comprising an immunoglobulin hinge region (pg. 311, example 20).
In regards to claim 71, the limitations of claim 1 are disclosed as discussed above. Sather further discloses a CD28-derived transmembrane domain (pg. 311, example 20).
In regards to claim 74, 77, and 80, the limitations of claim 1 are disclosed as discussed above. Sather further discloses an intracellular signaling domain of 4-1BB and CD3zeta (pg.311, example 20).
In regards to claim 83, the limitations of claim 1 are disclosed as discussed above. Sather further discloses the CAR sequence of the amino acid sequence of SEQ ID NO:37. While it is noted that at least 95% identity to the listed sequence could not be found, SEQ ID NO:37 corresponds to the functional sequences listed through claim 86 (see claim 86 rejection below). Additional amino acid sequences provide no further functional limitations and therefore do not overcome the nonobvious rejection.
In regards to claim 94, the limitations of claim 1 are disclosed as discussed above. Sather further discloses a polynucleotide encoding the CAR construct (pg.311, example 20).
In regards to claim 102, the limitations of claims 1 and 94 are disclosed as discussed above. Sather further discloses a vector comprising the polynucleotide of claim 94 (pg.311, example 20).
In regards to claim 106 and 111, the limitations of claim 1 are disclosed as discussed above. Sather further discloses using a T cell for the expression of the CAR construct (pg.311, example 20).
In regards to claims 123, the limitations of claim 1 and 106 are disclosed as discussed above. Sather further discloses the use of the CAR cell in a pharmaceutical composition (abstract).
In regards to claim 133, the limitations of claim 1 and 106 are disclosed as discussed above. Sather further discloses the method of using the CAR cells for the treatment of diseases (abstract).
Claim 6 is rejected under 35 U.S.C. 103 as being unpatentable over Sather, et al. (WO 2020/092854 A2) in view of Brinkman, et al. (MABS 2017 9:2, 182-212).
In regard to claim 6, Sather discloses a bispecific CAR comprising an extracellular domain comprising a heavy chain and light chain region of a GPRC5D-binding domain and a heavy and light chain region of a BCMA-binding domain, a spacer, a transmembrane domain, and an intracellular signaling domain (pg. 311, example 20). Sather does not disclose an extracellular domain comprising from amino to carboxy terminus: the VH region of GPRC5D, the VL and VH regions of BCMA, and the VL region of GPRC5D binding domains.
Brinkman teaches various bispecific constructs for use in therapeutic treatment. Particularly, Brinkman teaches a bispecific construct of sandwiching the variable regions of one antigen binding domain between the variable regions of the other antigen binding domain, e.g. VH1-VL2-VH2-VL1 (See Fig. 2, box 3 and pg. 186).
It would have been obvious to a person of ordinary skill in the art to apply the antigen binding domain pattern of Brinkman to the bispecific CAR of Sather to make the invention of claim 6. Sather teaches making a bispecific CAR for the binding domains of GPRC5D and BCMA for pharmaceutical treatment in humans. Brinkman teaches a pattern of design for bispecific antibodies that allows for compact dimerization during targeted binding that can retarget effector cells. The ability to retarget effector cells would lead to improved potency for treatment. Additionally, the use of dimers to target cells would decrease antigen-independent signaling leading to decreased side effects from the treatment. Therefore, it would be obvious to a person of ordinary skill in the art, prior to the effective filing date, to combine the teachings of Sather with the teachings of Brinkman to create the bispecific CAR T-cell of the present claimed invention to improve the potency of treatment and decrease side effects.
Claims 86-89 are rejected under 35 U.S.C. 103 as being unpatentable over Sather, et al. (WO 2020/092854 A2) in view of Brinkman, et al. (MABS 2017 9:2, 182-212).
In regard to claim 86, Sather discloses a bispecific CAR comprising an extracellular domain comprising a GPRC5D-binding domain and BCMA-binding domain (pg. 311, example 20). Sather also discloses the specific amino acid sequences for the VH binding region for GPRC5D CDR-1, 2, and 3, the VL region of BCMA CDR-1, 2, and 3, the VH region for BCMA CDR-1, 2, and 3, and the VL region of GPRC5D CDR-1, 2, and 3 (SEQ ID NOs:298, 301). Sather also discloses the amino acid sequence of the linker set forth in SEQ ID NO:17 and 21, the spacer in SEQ ID NO:27, the transmembrane domain in SEQ ID NO:28, and the intracellular signaling domain of SEQ ID NOs:29 and 30 (SEQ ID NO:50, 72). Sather also discloses the amino acid sequence of a CAR from amino to carboxy terminus of the extracellular domain including linker SEQ ID NO:17 between the variable regions, a spacer of SEQ ID NO:27, a transmembrane domain of SEQ ID NO:28, and an intracellular signaling domain of SEQ ID NOs:29 and 30 (SEQ ID NO:72).
However, Sather does not disclose a bispecific CAR of the amino acid sequences, from amino to carboxy terminus of the VH region of GPRC5D CDRs-1, 2, and 3, linker of SEQ ID NO:21, VL region of BCMA CDRs-1, 2, and 3, linker of SEQ ID NO:17, VH region of BCMA CDRs-1, 2, and 3, linker of SEQ ID NO:21, VL region of GPRC5D CDRs-1, 2, and 3, a spacer of SEQ ID NO:27, transmembrane domain of SEQ ID NO:28, and the intracellular signaling domain of SEQ ID NOs: 29 and 30.
Brinkman teaches a pattern for designing bispecific CARs where the variable regions for one of the antigen binding domain is sandwiched between the variable region of the other antigen binding domain, e.g. VH1-VL2-VH2-VL1 (Fig. 2, box 3, also see pg. 186). Brinkman also teaches SEQ ID NO:21 (GGGGS) as a useful linker sequence between the variable regions of the extracellular domain portion for this type of construct (pg. 185). Brinkman further teaches this design of CAR antigen binding domains allows for compact dimers to be created for use in treatment. These dimers can be used to retarget effector cells and molecules.
It would have been obvious to one of ordinary skill in the art to apply the antigen binding domain construct taught in Brinkman to the amino acid sequences disclosed in Sather to create the bispecific CAR construct of the claimed invention. Sather teaches the specific amino acid sequences for the CDR regions of the heavy and light chains for the GPRC5D and BCMA-binding domains. Sather also teaches the specific amino acid sequences for the linker sequences of the extracellular domain, the spacer region, the transmembrane domain, and the intracellular signaling domain. Brinkman teaches a construct for the bispecific antigen binding domains that will produce a target for treatment that is improved in potency and decreased antigen-independent signaling. Therefore, it would have been obvious to one of the ordinary skill in the art prior to the effective filing date to combine the teaching of Brinkman with the disclosure of Sather to produce the bispecific CAR constructs of the present claimed invention.
In regards to claim 87, the limitations of claim 86 are disclosed as discussed above, including the functional sequences of the extracellular domain. While it is noted that the exact listed sequence could not be found, SEQ ID NO:83 corresponds to the functional sequences of the extracellular domain of the bispecific CAR described in claim 86. Additional amino acid sequences provide no further functional limitations and therefore do not overcome the nonobvious rejection.
In regards to claim 88, the limitations of claim 86 are disclosed as discussed above, including the functional sequences of the CAR. While it is noted that the exact listed sequence could not be found, SEQ ID NO:37 corresponds to the functional sequences of the bispecific CAR described in claim 86. Additional amino acid sequences provide no further functional limitations and therefore do not overcome the nonobvious rejection.
In regards to claim 89, the limitations of claim 86 are disclosed as discussed above, including the functional sequences of the bispecific CAR. While it is noted that the exact listed polynucleotide sequence could not be found, SEQ ID NO:119 corresponds to the functional polynucleotide sequences of the bispecific CAR described in claim 86 that can be determined through the listed amino acid sequences. Additional polynucleotide sequences provide no further functional limitations and therefore do not overcome the nonobvious rejection.
Claims 188 and 189 are rejected for being unpatentable over Sather, et al. (WO 2020/092854 A2, cited in IDS from 1/4/2024) in view of Sather (WO 2020/092854 A2, cited in IDS from 1/4/2024).
In regard to the claim limitations for 188 and 189, Sather anticipates the limitations of claims 27 and 186 in example 20 of the disclosure. However, Sather example 20 does not disclose the use of the CAR cell within a pharmaceutical composition or the administration of the CAR cell to a subject for treating the disease. Sather does teach the use of CAR cells within a pharmaceutical composition and for the administration of the CAR cell to a subject for treating a disease (abstract).
It would have been obvious to a person having ordinary skill in the art prior to the effective filing date to add the CAR cell of example 20 into a pharmaceutical composition or to administer the cell to a subject for treating a disease or condition.
Conclusion
In summary, claims 1-2, 5-6, 20, 27, 37, 40, 44, 48, 62-63, 71, 74, 77, 80, 83, 86-89, 94, 102, 106, 111, 123, 133, 184-189 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LINDSAY DUNN whose telephone number is (571)272-5825. The examiner can normally be reached Monday-Friday 8-4:30.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Daniel Kolker can be reached at 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LINDSAY DUNN/Examiner, Art Unit 1644
/DANIEL E KOLKER/Supervisory Patent Examiner, Art Unit 1644