DETAILED ACTION
Claims 1-20 are currently pending and under examination in the present 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
Priority for the present application claimed benefit of applications PCT/CN2022/073808 and provisional application 63/141,621. Claims of the priority document were reviewed and deemed to support the claims of the present application. Therefore, priority and the effective filing date of 1/26/2021 is granted.
Claim Interpretation
Claim 1 recites a “chimeric antigen receptor.” Chimeric is defined as referring to a combination of two separate genetic elements combined through human engineering. It is noted that the limitations of claim 1 are drawn to the judicial exception of a product of nature. However, it has been determined that referring to the claimed invention as “chimeric” applies significantly more than just the judicial exception. Therefore, the present claimed invention has been deemed subject matter eligible under 35 U.S.C. 101.
Claim Rejections - 35 USC § 112
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 1-20 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 claims 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. This is a written description rejection.
An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). Claim 1 lacks written description because it presents a broad genus claim while the disclosure only describes a narrow species without considering the genus.
The limitations of claim 1 are directed to a CAR polypeptide for expression in NK cells containing an extracellular binding domain, a transmembrane domain, and an intracellular domain comprising either an intracellular signaling domain from a NK cell receptor, an intracellular signaling domain from an NK cell membrane-bound signaling adaptor protein, or an intracellular co-stimulatory domain from a co-stimulatory receptor. Morgan, et al. (Morgan, M., Frontiers in Immunology, Aug. 7, 2020, 11:1965) presents the generic structure of a CAR cell as including an extracellular binding domain, a transmembrane domain, and one or more intracellular signaling domains (Morgan, pg. 2 column 1. Paragraph 3, lines 6-13, also Fig. 1).
As evidenced by Morgan, the invention of claim 1 represents a broad genus of a CAR construct. The present disclosure further describes a specific NK CAR construct using specific signaling molecules and amino acid sequences. This specific NK CAR construct is not descriptive of the entire genus of CAR constructs as a whole since that would include CAR-T cell constructs and CAR constructs composed of T and NK cell elements. Therefore, claim 1 as evidenced by Morgan lacks written description for the present claimed invention as considered at the time of the application.
The limitations of claims 5, 11, 13-15 and 18-20 fail to add any meaningful limitations to overcome the written description rejection. Claim 5 recites an intracellular domain comprising a self-cleaving peptide or a cytokine. Claim 11 recites a signal peptide located N-terminal to the extracellular binding domain. Claim 13 recites a detectable marker distal to the extracellular binding domain. Claim 14 recites a linker domain distal to the extracellular binding domain or proximal to the signal peptide. Claim 15 recites a spacer domain located between the extracellular binding domain and the transmembrane domain. Claim 18 recites a population of NK cells. Claim 19 recites a method of increasing NK cell activation using the CAR NK of claim 1. Claim 20 recites a method of treating a subject in need of CAR-based therapy using the CAR NK cell of claim 1. None of the listed limitations provide a basis for overcoming the lack of written description as discussed above in claim 1.
Therefore, claims 1, 5, 11, 13-15, and 18-20 lack written description under 35 U.S.C. 112(a) for failing to claim a narrow species among the claimed broad genus.
Claims 2-4, 6-10, 12, and 16-17 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. This is a written description rejection.
An original claim may lack written description support when (1) the claim defines the invention in functional language specifying a desired result but the disclosure fails to sufficiently identify how the function is performed or the result is achieved or (2) a broad genus claim is presented but the disclosure only describes a narrow species with no evidence that the genus is contemplated. See Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1349-50 (Fed. Cir. 2010) (en banc). Claims 2-4, 6-10, 12, and 16-17 lack written description because they define an invention in functional language specifying a specific result but fail to disclose how the result is achieved.
Claim 2 recites the CAR polypeptide of claim 1 with the limitation of the intracellular signaling domain comprising, “the amino acid sequence of one of SEQ ID NOs:7-10 or an amino acid sequence that is at least 80% identical to one of SEQ ID NOs: 7-10.” This pattern of claiming sequences is repeated in claim 3 with SEQ ID NOs:11-12, claim 4 with SEQ ID NOs:15-16, claim 6 with SEQ ID NOs:19-20, claim 7 with SEQ ID NOs:23-24, claim 8 with SEQ ID NOs:29-32 or 117-118, claim 10 with SEQ ID NOs:35-36, claim 12 with SEQ ID NO:38, claim 16 with SEQ ID NO:44, and claim 17 with SEQ ID NOs:80-114.
The claim limitations mentioned above of claims 2-4, 6-10, 12, and 16-17 fail to support written description because the claims do not identify how the function is performed or the result is achieved. The above claims define the invention in functional language by providing specific amino acid sequences to create the element claimed. However, by not clearly defining the amino acid sequence either in full or at least 80% the claims fail to sufficiently identify how the functional element of the CAR cell is achieved.
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 13 and 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 13 recites “a detectable marker distal to the extracellular binding domain.” It is unclear the location of the detectable marker as “distal” could mean located on either side of the extracellular binding domain. It is suggested that applicant re-write the claim to clearly indicate the location of the detectable marker to overcome this rejection.
Claim 14 recites “a linker domain distal to the extracellular binding domain and/or proximal to the signal peptide.” It is unclear where the location of the linker domain is considering the use of the words “distal” to the extracellular domain, “proximal” to the signal peptide combined with the connection of “and/or” means that the linker domain could be located any place in the extracellular region. It is suggested that applicant re-write the claim to more clearly indicate the location of the linker domain 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 1-8 and 10-17 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by “Suri” (WO 2018/161017 published 09/07/2018).
In regards to claim 1, Suri discloses a chimeric antigen receptor (CAR) polypeptide for expression in natural killer (NK) cells comprising: a) an extracellular binding domain; b) a transmembrane domain; and c) an intracellular domain comprising at least one of the following: i) an intracellular signaling domain from an NK cell receptor; ii) an intracellular signaling domain from an NK cell membrane-bound signaling adaptor protein; and/or iii) an intracellular co-stimulatory domain from a co-stimulatory receptor (See pg. 4 [0016]).
In regards to claim 2, Suri discloses the limitations of claim 1 as described above. Suri further discloses the NK cell receptor: (a) is selected from a group consisting of: (i) Natural Killer Cell Receptor 2B4 (See Suri pg. 56 [00215] line 9 “SLAMF4 (CD244, 2B4)”) (ii) Natural Killer-T-and-B-cell antigen (NTB-A) (See Suri pg. 56 [00215] line 10, “SLAMF6 (NTB-A, Ly108)”) (iii) CD-2 like receptor activating cytotoxic cells (CRACC) (See Suri pg. 56 [00215] line 1); and (iv) cluster of differentiation 2 (CD2) (See Suri pg. 55 [00214] line 9); or (b) intracellular signaling domain comprises the amino acid sequence of one of SEQ ID NOs:7 or an amino acid sequence that is at least 80% identical to one of SEQ ID NO:7. It is specifically noted that Suri discloses SEQ ID NO:268 on pg. 57, which matches instant SEQ ID NO:7 100%.
In regards to claim 3, Suri discloses the limitations of claim 1 as described above. Suri further discloses the NK cell membrane bound signaling adaptor protein of CD3-zeta (See Suri pg. 5 [0021] lines 1-2); or intracellular signaling domain the amino acid sequence of SEQ ID NO:11 or at least 80% identical to SEQ ID NO:11. It is specifically noted that Suri discloses SEQ ID NO:338 on pg. 60, which matches instant SEQ ID NO:11 100%.
In regards to claim 4, Suri discloses the limitations of claim 1 as described above. Suri further discloses the co-stimulatory receptor 4-1BB (See Suri pg. 5 [0022]) and the intracellular co-stimulatory domain comprising the amino acid sequence of SEQ ID NO:15 or at least 80% of SEQ ID NO:15. It is specifically noted that Suri discloses SEQ ID NO:288 on pg. 57, which matches instant SEQ ID NO:15 97.6%.
In regards to claim 5, Suri discloses the limitations of claim 1 as described above. Suri further discloses the intracellular domain comprising at least one self-cleaving peptide (See Suri pg. 9 [0051]) or a cytokine (See Suri pg. 93 [00245]).
In regards to claim 6, Suri discloses the limitations of claim 1 and 5 as described above. Suri further discloses the self-cleaving peptide: a) P2A (See Suri pg. 87-88 see the description box in the chart corresponding to SEQ ID NO:1016, 1017, and 1018) and the amino acid sequence or at least 80% identical to one of SEQ ID NOs: 19. It is specifically noted that Suri discloses SEQ ID NOs:1016, 1017, and 1018 on pg. 87-88, which contains 100% of instant SEQ ID NO:19 within the disclosed sequences.
In regards to claim 7, Suri discloses the limitations of claim 1 and 5 as described above. Suri further discloses the cytokine is Il-15 or IL-21, (See Suri pg. 93 [00245]).
In regard to claim 8, Suri discloses the limitations of claim 1 as described above. Suri further discloses the transmembrane domain of CD8 (See Suri pg. 5 [0025]) and the amino acid sequence or at least 80% of the amino acid sequence of SEQ ID NO:32. It is specifically noted that Suri discloses SEQ ID NO:1016, 1017, and 1018 on pg. 87-88, which contains 100% of instant SEQ ID NO:32 within the disclosed sequences.
In regard to claim 10, Suri discloses the limitations of claim 1 as described above. Suri further discloses an extracellular binding domain that is a) an antibody, an antigen-binding fragment thereof, a F(ab) fragment, a F(ab') fragment, a single chain variable fragment (scFv), or a single-domain antibody (sdAb) (See Suri pg. 4 [0018]); b) specifically binds to a tumor-associated antigen (See Suri pg. 48 [00198]); or c) comprises the amino acid sequence of one of SEQ ID NOs: 35 or an amino acid sequence that is at least 80% identical to one of SEQ ID NOs: 35. It is specifically noted that Suri discloses SEQ ID NO:1016, 1017, and 1018 on pg. 87-88, which contains 100% of instant SEQ ID NO:35 within the disclosed sequences.
In regard to claim 11, Suri discloses the limitations of claim 1 as described above. Suri further discloses a signal peptide located at the N- terminal to the extracellular binding domain (See Suri pg. 19 [00121]).
In regard to claim 12, Suri discloses the limitations of claim 1 and 11 as described above. Suri further discloses the signal peptide: a) is a CD8 signal peptide (See Suri pg. 76, description box for SEQ ID NO:628) and the amino acid sequence of SEQ ID NO: 38 or an amino acid sequence that is at least 80% identical to SEQ ID NO: 38. It is specifically noted that Suri discloses SEQ ID NO:628 on pg. 76, which matches 100% of instant SEQ ID NO:38.
In regard to claim 13, Suri discloses the limitations of claim 1 as described above. Suri further discloses a detectable marker distal to the extracellular binding domain (See Suri pg. 19 [00121]).
In regard to claim 14, Suri discloses the limitations of claim 1 and 11 as described above. Suri further discloses a linker domain distal to the extracellular binding domain and/or proximal to the signal peptide (See Suri pg. 19 [00121]).
In regard to claim 15, Suri discloses the limitations of claim 1 as described above. Suri further discloses a spacer domain located between the extracellular binding domain and the transmembrane domain (See Suri pg. 63 [00222] lines 1-2).
In regard to claim 16, Suri discloses the limitations of claim 1 and 15 as described above. Suri further discloses the spacer domain comprises a) a CD8 hinge domain (See Suri pg. 68 description box for SEQ ID NO:440); or b) the amino acid sequence of SEQ ID NO: 44 or an amino acid sequence that is at least 80% identical to SEQ ID NO: 44. It is specifically noted that Suri discloses SEQ ID NO:44 on pg. 68, which matches 100% of instant SEQ ID NO:44.
In regard to claim 17, Suri discloses the limitations of claim 1 as described above. Suri further discloses the polypeptide comprises the amino acid sequence of at least 80% identical to one of SEQ ID NOs: 80-84. It is specifically noted that Suri discloses SEQ ID NO:1006 on pgs. 84-85, which matches 89.9% of instant SEQ ID NO:80 and matches 98.4% of instant SEQ ID NO:81. Suri further discloses SEQ ID NO:1008 on pg. 85, which matches 93.2% of instant SEQ ID NO:82 and matches 84.3% of SEQ ID NO:83. Suri further discloses SEQ ID NO:1017 on pg. 88, which matches 80.8% of SEQ ID NO:84.
Claims 1, 8-10, and 18-20 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by “Kaufman” (US 2018/0002438 A1 published 01/04/2018).
In regard to claim 1, Kaufman discloses a chimeric antigen receptor (CAR) polypeptide for expression in natural killer (NK) cells comprising: a) an extracellular binding domain; b) a transmembrane domain; and c) an intracellular domain comprising at least one of the following: i) an intracellular signaling domain from an NK cell receptor; ii) an intracellular signaling domain from an NK cell membrane-bound signaling adaptor protein; and/or iii) an intracellular co-stimulatory domain from a co-stimulatory receptor (See Kaufman pg. 1 [0002]).
In regard to claim 8, Kaufman discloses the claim limitations of claim 1 as described above. Kaufman further discloses the transmembrane domain of a transmembrane domain of a natural NK cell receptor (See Kaufman pg. 1 [0007]).
In regard to claim 9, Kaufman discloses the claim limitations of claims 1 and 8 as described above. Kaufman further discloses the transmembrane domain of the natural NK cell receptor is selected from the group consisting of Natural Killer Group 2D (NKG2D) and Natural Killer Cell P46-Related Protein (NKp46) (See Kaufman pg. 1 [0007]).
In regard to claim 18, Kaufman discloses the claim limitations of claim 1 as described above. Kaufman further discloses a natural killer (NK) cell or population thereof comprising the polypeptide of claim 1 (See Kaufman pg. 1 [0008]).
In regard to claim 19, Kaufman discloses the claim limitations of claim 1 as described above. Kaufman further discloses a method of increasing the activation of an NK cell or population thereof comprising contacting the cell or population thereof with the polypeptide of claim 1 (See Kaufman abstract).
In regard to claim 20, Kaufman discloses the claim limitations of claim 1 as described above. Kaufman further discloses a method of treating a subject in need of a CAR-based therapy comprising administering to the subject a therapeutically effective amount of the CAR-based therapy comprising the polypeptide of claim 1 (See Kaufman pg. 1 [0009]).
Conclusion
In summary, claims 1-20 are rejected.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. WO2019/178382 A1 (Qin) published on September 19, 2019 discloses the CAR construct of SEQ ID NO:18 that is 92.4% identical to the SEQ ID NO:107 of the present application and 97.8% identical to SEQ ID NO:106.
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/LINDSAY DUNN/
Examiner, Art Unit 1644
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642