DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application is being examined under the pre-AIA first to invent provisions.
2. Claims 1-30 are pending and under examination.
Information Disclosure Statement
3. The information disclosure statements (IDS) submitted on 11/6/2023 and 7/8/2024 have been considered by the examiner.
Specification
4. The disclosure is objected to for referring an amino acid sequence with SEQ ID NO: 5, see [0004], [0016], [0023] for example. SEQ ID NO:5 is skipped in the sequence listing under ST.26 for having less than four specifically defined amino acids.
SEQ ID NOs containing prohibited sequences (skipped sequences) do not have any sequence data in sequence listing. Prohibited sequences are those with <10 specifically defined nucleotides or <4 specifically defined amino acids.
Applicant is required to file an amended specification with replacement of the sequence identifiers corresponding to skipped sequences with the actual sequence; a statement that no new matter is added; and either:
File an affidavit/declaration under 37 CFR 1.132 showing that a bona fide attempt was made at the time of filing to submit a sequence listing with a sequence for the SEQ ID NO that is entered as a skipped sequence under ST.26; OR
Reference a priority document with a disclosure of the sequence that corresponds to the SEQ ID NO with a skipped sequence.
Claim Objections
5. Claims 8 and 9 are objected to for reciting “and/or”. The claims encompass a CAR comprises two transmembrane domains.
Claim Rejections - 35 USC § 112
6. 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.
7. Claims 1-30 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.
Claims 1-30 are indefinite for reciting SEQ ID NO: 5. SEQ ID NO: 5 contains a prohibited sequence (a skipped sequence) under ST.26. Prohibited sequences are those with <10 specifically defined nucleotides or <4 specifically defined amino acids. These SEQ ID NOs do not have any sequence data in sequence listing. Therefore, the metes and bounds of the claimed invention cannot be determined and the claims are indefinite.
Applicant should amended the claims to replace these SEQ ID NOs with the actual sequences, if originally disclosed.
In this office action, SEQ ID NO:5 is interpreted as AAS according to parent application no. 16/869,792.
Claim Rejections - 35 USC § 112
8. 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.
9. Claims 14 and 16-18 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.
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor’s contribution to the field of art as described in the patent specification.’” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
For a claim to a genus, a generic statement that defines a genus of substances by only their functional activity does not provide an adequate written description of the genus. Reagents of the University of California v. Eli Lilly, 43 USPQ2d 1398 (CAFC 1997). The recitation of a functional property alone, which must be shared by the members of the genus, is merely descriptive of what the members of the genus must be capable of doing, not of the substance and structure of the members.
“[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention.
Lastly, even if a selection procedure is disclosed that was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision.
Claim 14 and 16-18 are drawn to an isolated host cell comprising a nucleic acid comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR), wherein the CAR comprises:(a) an antigen binding domain of an antibody which binds to CD22, (b) a transmembrane domain, and (c) an intracellular T cell signaling domain, wherein the antigen binding domain comprises an amino acid sequence comprising a heavy chain CDR1 comprising SEQ ID NO: 1, a heavy chain CDR2 comprising SEQ ID NO: 2, a heavy chain CDR3 comprising SEQ ID NO: 3, a light chain CDR1 comprising SEQ ID NO: 4, a light chain CDR2 comprising SEQ ID NO: 5, and a light chain CDR3 comprising SEQ ID NO: 6, wherein the CAR comprises an amino acid sequence at least 90% identical to any one of SEQ ID NOs: 22-24 (claim 14), the CAR comprises an amino acid sequence at least 90% identical to SEQ ID NO: 22 (claim 16), wherein the CAR comprises an amino acid sequence at least 90% identical to SEQ ID NO:23 (claim 17), wherein the CAR comprises an amino acid sequence at least 90% identical to SEQ ID NO: 24 (claim 18)
The limitation “at least 90% identical” allows changes (including amino acid substitution, deletion, and/or addition) in the transmembrane domain, and/or the intracellular signaling domain of SEQ ID NO: 22, 23 or 24. SEQ ID NO: 22, for example, has 484 amino acids, “at least 90% identical” allows up to 48 amino acid changes.
The specification does not disclose any variants (homologues) of SEQ ID NO: 22, 23 or 24. The specification therefore fails to disclose a representative number of species for the genus. The specification also fails to disclose a correlation between a structure and function (e.g. capable of inducing T cell signaling). The specification does not disclose which amino acids in any of SEQ ID NOs: 22-24 can be changed by substitution, addition, and/or deletion such that the resulting polypeptides still have the function of the corresponding domains.
Therefore, the written description is not commensurate in scope with the claimed invention because applicant only disclosed SEQ ID NOs:22-24.
Butler et al. (Frontiers in Bioengineering and Biotechnology, 2023, 11:1101122, pages 1-9) constructed a model library of chimeric antigen receptors signaling domain variants and used to demonstrate the ability to discern amongst chimeric antigen receptors containing different costimulatory domains (abstract). Butler et al. discloses that a rare, higher-signaling variant with frequency as low as 1 in 1000 could be identified in a high throughput setting (abstract). This work highlights unpredictability of mutations to the function of T cell co-stimulatory domains.
Applicant has not disclosed any relevant, identifying characteristics, such as structure or other physical and/or chemical properties, sufficient to show possession of the claimed genus. Mere idea or function is insufficient for written description; isolation and characterization at a minimum are required. A description of what a material does, rather than what it is, usually does not suffice. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
In the absence of structural characteristics that are shared by members of the genus of variants, and absence of a representative number of species to describe the genus, one of ordinary skill in the art would not consider that applicant was in possession of all the variants. Applicant was only in possession of SEQ ID NOs: 22-24.
Double Patenting
10. 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
11. Claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. 11,807,682. Although the claims at issue are not identical, they are not patentably distinct from each other.
The claims of the patent disclose a method of treating a hematological cancer that expresses CD22 in a human, the method comprising administering to the human an effective amount of a chimeric antigen receptor (CAR) T cell to treat the hematological cancer that expresses CD22 in the human; wherein the CAR comprises (a) an antigen binding domain of an antibody which binds to CD22, (b) a transmembrane domain, and (c) an intracellular T cell signaling domain, wherein the antigen binding domain comprises an amino acid sequence comprising a heavy chain CDR1 comprising SEQ ID NO: 1, a heavy chain CDR2 comprising SEQ ID NO: 2, a heavy chain CDR3 comprising SEQ ID NO: 3, a light chain CDR1 comprising SEQ ID NO: 4, a light chain CDR2 comprising SEQ ID NO: 5, and a light chain CDR3 comprising SEQ ID NO: 6, and wherein the CAR is the sole CAR expressed by the T cell,
wherein the cancer that expresses CD22 is a leukemia or a lymphoma, the leukemia is chronic lymphocytic leukemia, acute myeloid leukemia, hairy cell leukemia, acute lymphocytic leukemia (ALL), or hairy cell leukemia, the lymphoma is Hodgkin lymphoma, non-Hodgkin lymphoma or Burkitt's lymphoma,
wherein the antigen binding domain comprises a light chain variable region comprising an amino acid sequence comprising SEQ ID NO: 7, and a heavy chain variable region comprising an amino acid sequence comprising SEQ ID NO: 8.
the antigen binding domain comprises an amino acid sequence comprising SEQ ID NO: 9, wherein the antigen binding domain comprises a linker comprising SEQ ID NO: 11,
wherein the CAR further comprises a leader sequence comprising SEQ ID NO: 10,
wherein the transmembrane domain comprises i) a transmembrane portion of a CD8 and/or ii) a transmembrane portion of a CD28, the transmembrane domain comprises an amino acid sequence comprising SEQ ID NO: 12 or 18 and/or an amino acid sequence comprising SEQ ID NO: 15,
wherein the intracellular T cell signaling domain comprises one or more of i) an intracellular signaling portion of a CD28, ii) an intracellular signaling portion of CD137, and iii) an intracellular signaling portion of a CD3 zeta, the intracellular T cell signaling domain comprises an amino acid sequence comprising SEQ ID NO: 16 or 19, the intracellular T cell signaling domain comprises an amino acid sequence comprising SEQ ID NO: 13 or 20, the intracellular T cell signaling domain comprises an amino acid sequence comprising SEQ ID NO: 14, 17 or 21, wherein the CAR comprises an amino acid sequence comprising any one of SEQ ID NOs: 22-24,
wherein the intracellular T cell signaling domain comprises an intracellular signaling portion of a CD28 or comprises an intracellular signaling portion of a CD137 and wherein the CAR does not comprise an intracellular signaling domain of both CD28 and CD137.
The amino acid sequences of SEQ ID NOs: 1-24 are 100% identical to instant SEQ ID NOs: 1-24, respectively given that the instant application is a continuation application of the patent.
12. Claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,703,816. Although the claims at issue are not identical, they are not patentably distinct from each other
Claims 1-18 of U.S. Patent No. 10,703,816 disclose a method of treating hematological cancer in a human subject, the method comprising administering to the subject a host cell, or a population thereof, in an amount effective to treat the cancer in the subject, wherein the host cell is a T cell and comprises a recombinant expression vector, wherein the recombinant expression vector comprising a nucleic acid comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR) comprising (a) an antigen binding domain which binds to CD22 and comprises an amino acid sequence comprising a heavy chain CDR1 comprising SEQ ID NO: 1, a heavy chain CDR2 comprising SEQ ID NO: 2, a heavy chain CDR3 comprising SEQ ID NO: 3, light chain CDR1 comprising SEQ ID NO: 4, a light chain CDR2 comprising SEQ ID NO: 5, and a light chain CDR3 comprising SEQ ID NO: 6, (b) a transmembrane domain, and (c) an intracellular T cell signaling domain, the nucleotide sequence comprising SEQ ID NO: 25, 26, 27 or 28.
The claims are further limited, wherein the antigen binding domain comprising a light chain variable region comprising an amino acid sequence comprising SEQ ID NO: 7, or a heavy chain variable region comprising an amino acid sequence comprising SEQ ID NO: 8, the antigen binding domain comprising an amino acid sequence comprising SEQ ID NO: 9, the transmembrane domain comprising an amino acid sequence comprising SEQ ID NO: 12 or 18 (which is a CD8 transmembrane domain) and/or an amino acid sequence comprising SEQ ID NO: 15 (which is a CD28 transmembrane domain), the intracellular T cell signaling domain comprising an amino acid sequence comprising SEQ ID NO: 16 or 19 (which is a CD28 signaling domain) , the intracellular T cell signaling domain comprising an amino acid sequence comprising SEQ ID NO: 13 or 20 (which is a CD137 signaling domain), the intracellular T cell signaling domain comprising an amino acid sequence comprising SEQ ID NO: 14, 17 or 21 (which is a CD3 zeta signaling domain).
The amino acid sequences of SEQ ID NOs: 1-9, and 12-21 are 100% identical to instant SEQ ID NOs: 1-9 and 12-21, respectively. SEQ ID NOs: 26-28 encode instant SEQ ID NOs: 22-24, respectively. The CAR encoded by each of SEQ ID NOs: 26-28 comprises instant SEQ ID NO:10 (a leader peptide). The amino acid sequence of SEQ ID NO: 9 comprises instant SEQ ID NO:11.
13. Claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-18 of U.S. Patent No. 10,072,078, in view of June et al (WO 2012/079000A1, pub. date: 6/14/2012, effectively filed date: 12/9/2010, IDS filed on 11/6/2023).
Claims 1-18 of U.S. Patent No. 10/072,078 disclose a chimeric antigen receptor (CAR) comprising (a) an antigen binding domain which binds to CD22 and comprises an amino acid sequence comprising a heavy chain CDR1 comprising SEQ ID NO: 1, a heavy chain CDR2 comprising SEQ ID NO: 2, a heavy chain CDR3 comprising SEQ ID NO: 3, light chain CDR1 comprising SEQ ID NO: 4, a light chain CDR2 comprising SEQ ID NO: 5, and a light chain CDR3 comprising SEQ ID NO: 6, (b) a transmembrane domain, and (c) an intracellular T cell signaling domain.
The claims are further limited, wherein the antigen binding domain comprising a light chain variable region comprising an amino acid sequence comprising SEQ ID NO: 7, or a heavy chain variable region comprising an amino acid sequence comprising SEQ ID NO: 8, the antigen binding domain comprising an amino acid sequence comprising SEQ ID NO: 9, the antigen binding domain comprises a linker comprising SEQ ID NO: 11, and a leader sequence comprising SEQ ID NO:10, the transmembrane domain comprising an amino acid sequence comprising SEQ ID NO: 12 or 18 and/or an amino acid sequence comprising SEQ ID NO: 15, the intracellular T cell signaling domain comprising an amino acid sequence comprising SEQ ID NO: 16 or 19, the intracellular T cell signaling domain comprising an amino acid sequence comprising SEQ ID NO: 13 or 20, the intracellular T cell signaling domain comprising an amino acid sequence comprising SEQ ID NO: 14, 17 or 21, the CAR comprises SEQ ID NO: 22, 23 or 24.
The amino acid sequences of SEQ ID NOs: 1-24 are 100% identical to instant SEQ ID NOs: 1-24, respectively.
The claims of the patent do not disclose a method of treating leukemia or lymphoma using T cells modified to express the CAR.
June et al. teaches a method of treating leukemia or lymphoma in a subject comprising administering to the subject genetically modified T cell expressing a CAR that binds to CD22 (abstract, claims and page 5, lines 13-15).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have made T cells expressing the CAR of the patent and further used the CAR T cells to treat cancer in view of June. One would have been motivated to do so with a reasonable expectation of success because June et al. teaches using genetically modified T cell expressing a CAR that binds to CD22 to treat cancer (abstract, claims and page 5, lines 13-15).
14. Claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of U.S. Patent No. 10,738,116, in view of Copper et al. (WO 2009/091826A2, pub. date: 7/23/2009, IDS filed on 11/6/2023).
Claims 1-24 of U.S. Patent No. 10,738,116 disclose a method of treating a hematological malignancy in a human patient in need thereof, the method comprising administering to the patient a population of T cells expressing a nucleic acid encoding a CAR in an amount effective to treat the malignancy, wherein the CAR has antigenic specificity for CD19 and CD22, and comprises an anti-CD22 antigen binding domain, an anti-CD19 antigen binding domain, a hinge domain, a transmembrane domain, and an intracellular T cell signaling domain, wherein the CAR comprises the amino acid sequence of SEQ ID NO: 23 or SEQ ID NO: 24, wherein the CAR comprises a CD8 transmembrane domain and a CD8 hinge domain, the CD8 transmembrane domain comprises the amino acid sequence of SEQ ID NO: 26 and the CD8 hinge domain comprises the amino acid sequence of SEQ ID NO: 33, the intracellular T cell signaling domain comprises a 4-1BB intracellular T cell signaling sequence, a CD3 zeta (ζ) intracellular T cell signaling sequence, the 4-1BB intracellular T cell signaling sequence comprises the amino acid sequence of SEQ ID NO: 27, the CD3ζ intracellular T cell signaling sequence comprises the amino acid sequence of SEQ ID NO: 28. The claims of the patent further discloses a nucleic acid comprising a nucleotide sequence encoding the CAR and the nucleic acid comprising the nucleotide sequence of SEQ ID NO: 31 or 32, a recombinant expression vector comprising the nucleic acid, and an isolated host cell comprising the recombinant expression vector.
The amino acid sequence of SEQ ID NO:24 comprises instant SEQ ID NOs: 1-9, and 11. The amino acid sequences of SEQ ID NO:26, 27, 28 are 100% identical to instant SEQ ID NO:12, 20, 17, respectively.
The claims of the patent do not disclose that the CAR comprises a leader peptide of SEQ ID NO:10, and the CAR comprises an intracellular signaling domain of CD3[Symbol font/0x7A], CD28 and 4-1BB (CD137).
Cooper et al. teaches a human CD19-specific chimeric antigen receptor comprising a GM-CSFα leader peptide having the amino acid sequence of SEQ ID NO:5 (page 24, Example 3 and Fig. 8). The amino acid sequence of SEQ ID NO:5 is 100% identical to instant SEQ ID NO:10. Cooper further teaches that the intracellular domain of a CAR can comprise an intracellular signaling domain of human CD3[Symbol font/0x7A] and one or more intracellular domains of CD28 and 4-1BB ([0049]).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have included a leader peptide in the CAR of the patent in view of Cooper. One would have been motivated to do so with a reasonable expectation of success as the peptide leader has been included in CARs for targeting newly synthesized protein to secretory pathway, as evidenced by Cooper.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made and one would have been motivated to have modified the CAR of the patent to comprise an intracellular signaling domain of human CD3[Symbol font/0x7A] and one or more intracellular domains of CD28 and 4-1BB in view of Cooper. One would have had a reasonable expectation of success because Cooper teaches that the intracellular domain of a CAR can comprise an intracellular signaling domain of human CD3[Symbol font/0x7A] and one or more intracellular domains of CD28 and 4-1BB ([0049]).
15. Claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,980,640, in view of Copper et al. (WO 2009/091826A2, pub. date: 7/23/2009, IDS filed on 11/6/2023).
The claims of the patent disclose a method of treating cancer in a mammal, the method comprising administering to the mammal a host cell comprising a CAR construct, wherein the CAR construct a chimeric antigen receptor (CAR) amino acid construct comprising: (a) a cleavable domain; (b) a first CAR comprising a first antigen binding domain, a first transmembrane domain, and a first intracellular T cell signaling domain; and (c) a second CAR comprising a second antigen binding domain, a second transmembrane domain, and a second intracellular T cell signaling domain, the first or second transmembrane domain comprises a CD8 transmembrane domain comprising the amino acid sequence of SEQ ID NO: 19, the first and second T cell intracellular domain comprises a first or second 4-1BB intracellular T cell signaling sequence comprising the amino acid sequence of SEQ ID NO: 20 or a first or second CD3 intracellular T cell signaling sequence comprising the amino acid sequence of SEQ ID NO: 21, wherein the CAR construct comprises the amino acid sequence of SEQ ID NO: 48, 49, 50, 51, 52, 63-69, or 70, wherein the cancer is a hematological malignancy.
The claims of the patent disclose a chimeric antigen receptor (CAR) amino acid construct comprising: (a) two or more cleavable domains; (b) a first CAR comprising a first antigen binding domain, a first transmembrane domain, and a first intracellular T cell signaling domain; and (c) a second CAR comprising a second antigen binding domain, a second transmembrane domain, and a second intracellular T cell signaling domain; wherein the first and second CARs are linked through the two or more cleavable domains, and (i) wherein the first antigen binding domain comprises the heavy chain variable region CDR sequences of SEQ ID NOS: 4, 6, and 8 and the light chain variable region CDR sequences of SEQ ID NOS: 12, 14 and 16, and wherein when the first CAR is cleaved from the construct, the first antigen binding domain has antigenic specificity for CD22; or (ii) wherein the first antigen binding domain comprises the light chain variable region CDR sequences of SEQ ID NOS: 24, 26, and 28, and the heavy chain variable region CDR sequences of SEQ ID NOS: 32, 34 and 36, and wherein when the first CAR is cleaved from the construct, the first antigen binding domain has antigenic specificity for CD19,
wherein the first or second transmembrane domain comprises a CD8 transmembrane domain and a CD8 hinge domain, and wherein the CD8 transmembrane domain comprises the amino acid sequence of SEQ ID NO: 191 and the CD8 hinge domain comprises the amino acid sequence of SEQ ID NO: 18, 86,
the first or second intracellular T cell signaling domain comprises a 4-1BB intracellular T cell signaling sequence, and wherein the 4-1BB intracellular T cell signaling sequence comprises the amino acid sequence of SEQ ID NO: 20, the first or second intracellular T cell signaling domain comprises a CD3 zeta (ζ) intracellular T cell signaling sequence, and wherein the CD3ζ intracellular T cell signaling sequence comprises the amino acid sequence of SEQ ID NO: 21, wherein the CAR comprises an amino acid sequence having 90% or greater sequence identity with, or comprising, any one of SEQ ID NOS: 49, 50, 51, or 52.
The claims of the patent further disclose a nucleic acid comprising a nucleotide sequence encoding the CAR amino acid construct, an isolated host cell comprising a recombinant expression vector comprising the nucleic acid, a pharmaceutical composition comprising a population of cells comprising the host cell, and a pharmaceutically acceptable carrier.
The claims of the patent further disclose a method of treating cancer in a mammal, the method comprising administering to the mammal a population of cells comprising the host cell in an amount effective to treat cancer in the mammal, wherein the cancer is a hematological malignancy, wherein the CAR comprises the amino acid sequence of SEQ ID NO: 52.
Each of the amino acid sequences of SEQ ID NO: 48-52 comprises instant SEQ ID NOs: 1-9. SEQ ID NO:48 comprises instant SEQ ID NOs: 1-13, 17, 21, and is 99.2% identical to instant SEQ ID NO:22, see sequence alignment below:.
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The claims of the patent do not disclose that the CAR comprises a leader peptide of SEQ ID NO:10, and the CAR comprises an intracellular signaling domain of CD3[Symbol font/0x7A], CD28 and/or 4-1BB (CD137).
Cooper et al. teaches a human CD19-specific chimeric antigen receptor comprising a GM-CSFα leader peptide having the amino acid sequence of SEQ ID NO:5 (page 24, Example 3 and Fig. 8). The amino acid sequence of SEQ ID NO:5 is 100% identical to instant SEQ ID NO:10. Cooper further teaches that the intracellular domain of a CAR can comprise an intracellular signaling domain of human CD3[Symbol font/0x7A] and one or more intracellular domains of CD28 and 4-1BB ([0049]).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have used the leader peptide of Cooper in the CAR of reference application in view of Cooper. One would have been motivated to do so with a reasonable expectation of success as the peptide leader has been included in CARs for targeting newly synthesized protein to secretory pathway, as evidenced by Cooper.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made and one would have been motivated to have modified the CAR of the patent to comprise an intracellular signaling domain of human CD3[Symbol font/0x7A] and one or more intracellular domains of CD28 and 4-1BB in view of Cooper. One would have had a reasonable expectation of success because Cooper teaches that the intracellular domain of a CAR can comprise an intracellular signaling domain of human CD3[Symbol font/0x7A] and one or more intracellular domains of CD28 and 4-1BB ([0049]).
16. Claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,802,142, in view of June et al. (WO 2012/079000A1, pub. date: 6/14/2012, effectively filed date: 12/9/2010, IDS filed on 11/6/2023) and Bruenker et al. (US 2012/0184718A1, pub. date: 7/19/2012).
The claims of the patent disclose an immunotherapy composition comprising: at least one multi-cistronic vector comprising a promoter operably linked to a multi-cistronic nucleic acid sequence encoding; two or more functional CARs comprising an extracellular antigen binding domain, a transmembrane domain, one or more non-identical intracellular signaling motifs, each comprising a non-identical amino acid sequence that is independently selected from the group consisting of the amino acid sequence of SEQ ID NOs. 54, 56, 60, and 62; and wherein the at least one multi-cistronic vector is used to genetically modify one or more lymphocyte populations.
The claims of the patent disclose a pharmaceutical composition comprising an antitumor effective amount of a population of human lymphocytes, wherein each cell of the population of human lymphocytes comprises (a) at least one multi-cistronic vector; (b) wherein each of the at least one multi-cistronic vector encodes two or more functional CARs comprising a non-identical amino acid sequence that is independently selected from the group consisting of the amino acid sequence of SEQ ID NO. 54, 56, 60, and 62; (c) wherein each comprising an extracellular antigen binding domain, a transmembrane domain, at least one linker domain, and one or more non-identical intracellular signaling motifs; and (d) wherein the extracellular antigen binding domain, the transmembrane domain, the at least one linker domain, and the one or more intracellular signaling motifs are covalently linked in each of the at least one multi-cistronic vector, wherein the at least one multi-cistronic vector is used to genetically modify one or more lymphocyte populations,
wherein the population of human lymphocytes is a population of T cells of a human having leukemia or lymphoma, wherein the leukemia is chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), or chronic myelogenous leukemia (CML), wherein the lymphoma is mantle cell lymphoma, non-Hodgkin's lymphoma or Hodgkin's lymphoma.
The amino acid sequences of SEQ ID NO: 54 comprises instant SEQ ID NOs: 1-8. 10, 12, 13, 16, 17 and 21. The amino acid sequence of SEQ ID NOs: 54 is 97.6% identical to instant SEQ ID NO:22, see sequence alignment below:
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The claims of the patent do not disclose a method of treating cancer using the immunotherapy composition. The claims of the patent do not disclose instant SEQ ID NO: 9 (which is SEQ ID NO:8-GGGGS linker-SEQ ID NO:7).
June et al. teaches a method of treating leukemia or lymphoma in a subject comprising administering to the subject genetically modified T cell expressing a CAR that binds to CD22 (abstract, claims and page 5, lines 13-15).
Bruenker et al. teaches making scFv by linking the VH and VL domain with a G4S linker ([0034])
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have used the immunotherapy composition of the reference application to treat cancer in view of June. One would have been motivated to do so with a reasonable expectation of success because June et al. teaches using genetically modified T cell expressing a CAR that binds to CD22 to treat cancer (abstract, claims and page 5, lines 13-15).
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have used the linker GGGGS to linker the VH and VL domain in view of Bruenker. One would have been motivated to do so with a reasonable expectation of success because Bruenker et al. teaches making scFv by linking the VH and VL domain with a G4S linker ([0034])
17. Claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 10,689,431, in view of Bruenker et al. (US 2012/0184718A1, pub. date: 7/19/2012).
The claims of the patent disclose a method of treating a subject having a hematological cancer the method comprising administering to the subject a pharmaceutical composition comprising an antitumor effective amount of a population of human lymphocyte cells, wherein each cell of the population of human lymphocyte cells comprises at least one multi-cistronic vector, each of the at least one multi-cistronic vector comprises a promoter operably linked to a multi-cistronic nucleic acid sequence encoding two or more functional CARs comprising an extracellular antigen binding domain, a transmembrane domain, and one or more non-identical intracellular signaling motifs, wherein each of the encoded two or more functional CARs comprises a non-identical amino acid sequence that is independently selected from the group consisting of the amino acid sequences of SEQ ID NO. 54, 56, 60, and 62, wherein the population of human lymphocyte cells are T cells that are autologous to the subject, and wherein
the population of human lymphocyte cells comprise T cells and dendritic cells obtained from a hematopoietic stem cell donor, the hematological cancer is leukemia, lymphoma, or multiple myeloma, the leukemia is chronic lymphocytic leukemia (CLL), acute lymphocytic leukemia (ALL), acute myeloid leukemia (AML), or chronic myelogenous leukemia (CML), the lymphoma is mantle cell lymphoma, non-Hodgkin's lymphoma or Hodgkin's lymphoma.
The amino acid sequences of SEQ ID NO: 54 comprises instant SEQ ID NOs: 1-8, 10-13, 16, 17, 19, 21.
The claims of the patent do not disclose instant SEQ ID NO: 9 (which is SEQ ID NO:8-GGGGS linker-SEQ ID NO:7).
Bruenker et al. teaches making scFv by linking the VH and VL domain with a G4S linker ([0034])
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have used the linker GGGGS to linker the VH and VL domain in view of Bruenker. One would have been motivated to do so with a reasonable expectation of success because Bruenker et al. teaches making scFv by linking the VH and VL domain with a G4S linker ([0034])
18. Claims 1-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 11,453,712, in view of Bruenker et al. (US 2012/0184718A1, pub. date: 7/19/2012).
The claims of the patent disclose a method of treating a subject having a CD19+, a CD20+, a CD22+ or a CD19+ and CD20+ lymphoma, the method comprising administering to the subject having the CD19+, the CD20+, the CD22+ or the CD19+ and CD20+ lymphoma a pharmaceutical composition comprising an antitumor effective amount of a population of human T cells, wherein the population of human T-cells are autologous to the subject, and wherein each cell of the population of human T-cells comprises at least one multi-cistronic vector, each of the at least one multi-cistronic vector comprises a promoter operably linked to a multi-cistronic nucleic acid sequence encoding two or more functional CARs, wherein at least one of the two or more functional CARs comprises two non-identical extracellular antigen binding domains, a transmembrane domain, and one or more non-identical intracellular signaling motifs, and comprises an amino acid sequence selected from the group consisting of SEQ ID NO: 10 and SEQ ID NO: 52, and the combination of the vectors results in the expression of at least two non-identical extracellular binding domains directed to the CD19+, the CD20+, the CD22+ or the CD19+ and CD20+ lymphoma thereby treating the subject, wherein the lymphoma is mantle cell lymphoma, non-Hodgkin's lymphoma or Hodgkin's lymphoma.
The amino acid sequences of SEQ ID NO: 10 comprises instant SEQ ID NOs: 1-8. 10, 12, 13, 16, 17 and 21. The amino acid sequence of SEQ ID NOs: 10 is 97.8% identical to instant SEQ ID NO:22, see sequence alignment below:
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788
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The claims of the patent do not disclose instant SEQ ID NO: 9 (which is SEQ ID NO:8-GGGGS linker-SEQ ID NO:7).
Bruenker et al. teaches making scFv by linking the VH and VL domain with a G4S linker ([0034])
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have used the linker GGGGS to linker the VH and VL domain in view of Bruenker. One would have been motivated to do so with a reasonable expectation of success because Bruenker et al. teaches making scFv by linking the VH and VL domain with a G4S linker ([0034])
19. Claims 1-30 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-31 of copending Application No. 18/502,993. Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
The claims of the copending application disclose a nucleic acid comprising a nucleotide sequence encoding a chimeric antigen receptor (CAR) that binds human CD22 (hCD22), wherein the hCD22 CAR comprises:(a) a leader sequence; (b) an antigen-binding domain that binds human CD22; (c) a transmembrane domain; and (d) an intracellular T cell signaling domain; wherein the leader sequence comprises a leader from human granulocyte macrophage colony- stimulating factor receptor alpha (hGM-CSFRa) having the amino acid sequence of SEQ ID NO: 10; wherein the antigen-binding domain binds hCD22 and comprises a heavy chain complementarity determining region 1 (VH CDR1) having the amino acid sequence of SEQ ID NO: 1, a heavy chain variable complementarity determining region 2 (VH CDR2) having the amino acid sequence of SEQ ID NO: 2, a heavy chain variable complementarity determining region 3 (VH CDR3) having the amino acid sequence of SEQ ID NO: 3), a linker having the amino acid sequence of SEQ ID NO: 11, a light chain variable complementarity determining region 1 (VL CDR1) having the amino acid sequence of SEQ ID NO: 4, a light chain variable complementarity determining region 2 (VL CDR2) having the amino acid sequence of SEQ ID NO: 5, and a light chain variable complementarity determining region 3 (VL CDR3) having the amino acid sequence of SEQ ID NO: 6; wherein the transmembrane domain comprises a transmembrane domain from CD8 (CD8 TM) having the amino acid sequence of SEQ ID NO: 12; and wherein the intracellular T cell signaling domain comprises an intracellular signaling domain from 4-1BB/CD137 having the amino acid sequence of SEQ ID NO: 13 and an intracellular signaling domain from CD3-zeta (CD3Q) having the amino acid sequence of SEQ ID NO: 14,
wherein the nucleotide sequence encoding an hCD22 CAR comprises a heavy chain variable region (VH) having the amino acid sequence of SEQ ID NO: 8, a linker having the amino acid sequence of SEQ ID NO: 11, and a light chain variable region (VL) having the amino acid sequence of SEQ ID NO: 7,
the nucleotide sequence encoding an hCD22 CAR comprises a single chain variable fragment (scFv) of an antibody having the amino acid sequence of SEQ ID NO: 9,
the nucleotide sequence encoding an hCD22 CAR comprises a nucleic acid having the sequence of SEQ ID NO: 25 and a nucleic acid having the sequence of SEQ ID NO: 26,
the nucleotide sequence encoding an hCD22 CAR comprises a nucleotide sequence encoding a CAR having the amino acid sequence of SEQ ID NO: 22.
The claims of the copending application further disclose recombinant expression vector comprising the nucleic acid, wherein the recombinant expression vector is a lentiviral expression vector, an isolated host cell comprising the recombinant expression vector wherein the isolated host cell is a T cell, wherein the T cell is isolated from a human subject having a hematological cancer expressing CD22, a population of isolated host cells comprising two or more of the isolated host cells of claim 12, a pharmaceutical composition comprising the recombinant expression vector or the isolated host cell, and a pharmaceutically acceptable carrier, and a method of treating a hematological cancer expressing CD22 in a human subject comprising administering the pharmaceutical composition to the human subject, wherein the hematological cancer expressing CD22 is a leukemia or lymphoma, the hematological cancer expressing CD22 is a lymphoma, and the lymphoma is a B cell lymphoma, Hodgkin's lymphoma, non- Hodgkin's lymphoma, or Burkitt's lymphoma.
The amino acid sequences of SEQ ID NOs: 1-24 are 100% identical to instant SEQ ID NOs: 1-24, respectively given that the instant application is a continuation application of the patent.
20. The Examiner has noticed the existence of nonstatutory obviousness-type double patenting (ODP) with other applications:
(i) claims 3, 6-14, 16-17, 23 and 26-30 of copending Application No. 17/752,966
(ii) claims 1, 4, 10, 33, and 35-45 of copending Application No. 18/465,233
(iii) claims 1, 9, 23-26 and 36-38 of copending Application No. 18/644,724,
in view of June et al. (WO 2012/079000A1, pub. date: 6/14/2012, effectively filed date: 12/9/2010, IDS filed on 11/6/2023), Copper et al. (WO 2009/091826A2, pub. date: 7/23/2009, IDS filed on 11/6/2023), and Bruenker et al. (US 2012/0184718A1, pub. date: 7/19/2012).
It is noted that due to time constraints, the examiner has not provided individual rejections for each and every ODP, however, applicants ARE required to respond to all of the enumerated patents or patent applications, and any others that applicants may be aware of.
Conclusion
21 No claims are allowed.
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/HONG SANG/Primary Examiner, Art Unit 1643
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