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 .
Election/Restrictions
Applicant’s election without traverse of Group II (3, 6, 15-17, 20, 22-26, 29, 31,
44, 46, 48, 49, 51, 53, 54, 60, 69, 75, 78, 79, 85, 91, 101, and 102) in the reply filed on 01/20/2026 is acknowledged. Claims 3, 6, 15-17, 20, 22-26, 29, 31, 34, 37, 41, 44, 46, 48, 49, 51, 53, 54, 60, 69, 75, 76, 78, 79, 85, 91, 101, and 102 are pending; claims 34, 37, 41, and 76 withdrawn from prosecution as being drawn to non-elected subject matter. Claims 3, 6, 15-17, 20, 22-26, 29, 31, 44, 46, 48, 49, 51, 53, 54, 60, 69, 75, 78, 79, 85, 91, 101, and 102 are examined.
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.
Claims 3, 6, 15-17, 20, 22-26, 29, 31, 49, 69, 75, 76, 78, 79, 85, 91, 101, and 102 are rejected under 35 U.S.C. 103 as being unpatentable over Albertson T. (WO2018223101-cited by Applicant) in view of Oliai et al. (Interleukin-1 blockade to prevent severe immune effector cell associated neurotoxicity syndrome; Trial in progress. Journal for ImmunoTherapy of Cancer 2019, 7(Suppl 1):P406).
The claims are drawn to a method of reducing the severity of, attenuating, and/or
preventing the onset of a toxicity in a subject (which may be human) to a cell therapy for treating the subject having or suspected of having a disease or disorder associated with B-cell maturation antigen (BCMA) expression, the method comprising administering to the subject at least two doses of an interleukin-1 receptor antagonist (IL- 1Ra) and the cell therapy comprising a dose of engineered T cells comprising a chimeric antigen receptor (CAR) specific for BCMA, wherein at least one dose of the at least two doses of IL-1Ra is administered within about or about 24 hours prior to the administration of the dose of engineered T cells; and at least one dose of the at least two doses of IL-1Ra is administered after the administration of the dose of engineered T cells. A dose of IL-1Ra is administered every 24 hours (q24h) on Days 2-5. The method may be practiced by administering to the subject at least 6 doses of an interleukin-1 receptor antagonist (IL- 1Ra) wherein the cell therapy is administered on Day 1 and:
(a) one dose of the IL-1Ra is administered within about or about 24 hours prior to the
administration of the dose of engineered T cells;
(b) one dose of the IL-1Ra is administered within about or about 3 hours prior to the
administration of the dose of engineered T cells on Day 1;
( c) four doses of the IL-1Ra are administered after the administration of the dose of
engineered T cells, wherein one dose of the four doses is administered each day on Days 2, 3, 4, and 5.
If the subject exhibits symptoms or signs of a cytokine release syndrome (CRS) after the administration of the dose of engineered T cells, at least one additional dose of IL-1Rais administered or a dose of IL-1Ra every 12 hours (q 12h) until the symptoms or
signs of CRS resolve. The IL-1Ra may be anakinra and have sequence corresponding to the SEQ ID NO:256. Each dose is between 50-200 mg. The toxicity may be CRS or neurotoxicity.
The dose of engineered T cells (which may be a combination of CD4+ and CD8+ cells) is between 1 x 107-1 x 109 cells. Prior to the administration of the dose of engineered T cells, the subject has been administered a lymphodepleting therapy comprising the administration of fludarabine at or about 20-40 mg/m2 body surface area daily, for 2-4 days, and/or cyclophosphamide at or about 200-400 mg/m2 body surface area of the subject daily, for 2-4 days.
The disease or disorder associated with BCMA expression is an autoimmune disease or disorder or a BCMA-expressing cancer (multiple myeloma). The subject may have a relapsed or refractory multiple myeloma.
Albertson disclosed a T-cell therapy comprising chimeric antigen receptors CAR
specific for BCMA and an antagonist IL-1 receptor (IL-1 R), anakinra, or in combination with an antibody drug conjugate for use in treating a disorder associated with a B-cell maturation antigen expression, toxicity, autoimmune disease multiple myeloma, lymphoma leukemia (abstract). The chimeric receptors, such as CARs, generally include an extracellular antigen binding domain, such as a portion of an antibody molecule, generally a variable heavy (VH) chain region and/or variable light (VL) chain region of the antibody, e.g., an scFv antibody fragment ([0536]) and may be anti-BCMA antibodies ([0538]). The dosage of cell is between 2 x 105 and 2 x 106 cells/kg (which given a human weight between 50-100 kg would yield a dosage between 1x 107 – 2 x 108). In some instances, where the subject is human, the CAR T cells are CD4+ and CD8+ T cells ([0271]).
The size or timing of the doses is determined as a function of the particular disease or condition in the subject. In some cases, the size or timing of the doses for a particular disease in view of the provided description may be empirically determined ([0262]-[0263]). The reference also teaches administering toxicity-targeting agent, that treats or ameliorates symptoms of a toxicity cell therapy, such as CRS or neurotoxicity, by targeting a cytokine receptor, with an antagonist or inhibitor of a cytokine, such IL-1 receptor (anakinra) ([0513], [0527]). The reference also disclosed that prior to the
administration, the subject has been preconditioned with a lymphodepleting therapy comprising the administration of fludarabine (20-40 mg/m2) and/or cyclophosphamide (200-400 mg/m2) daily for 2-4 days ([0112]).
Among the diseases, conditions, and disorders treated are autoimmune or inflammatory diseases and cancer (multiple myeloma) ([0242]).
In some embodiments, at least 70% of the subjects who, at or prior to the administration of the dose of cells had or were identified to have a relapse, optionally relapse within 12 months, following administration of an autologous stem cell transplant (ASCT) ([0051]).
Even though the reference identifies the use of IL-1R antagonist anakinra as an agent of reducing CRS or NT, it does not mention the dose to be used.
Oliai et al. uses Anakinra to prevent CRS or immune effector cell-associated neurotoxicity syndrome (ICANS) in CAR T-cell therapy targeting CD19. The reference is disclosing the first human trial of Anakinra to treat ICANS in B-cell lymphoma patients
treated with anti-CD19 CAR T-cells. Upon development of grade 1 ICANS, or grade 3 CRS (which is often followed by ICANS), participants will receive Anakinra 100 mg subcutaneously every 6 hours for at least 12 doses, or until ICANS returns to grade 1 in participants who develop grade 2 neurotoxicity.
Claims 44 and 53 are rejected under 35 U.S.C. 103 as being unpatentable over Albertson T. (WO2018223101-cited by Applicant) in view of Oliai et al. (cited supra) and in further view of Brent et al. (WO2016090320 -cited by Applicant).
The claims add the limitation that the extracellular antigen-binding domain comprises: a variable heavy chain (VH) comprising a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2) and a heavy chain complementarity determining region 3 (CDR-H3) contained within the sequence set forth in SEQ ID NO: 116 and a variable light chain (VL) comprising a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) contained within the sequence set forth in SEQ ID NO: 119; a VH comprising a CDR-H1, a CDR-H2 and a CDR-H3 sequences set forth in SEQ ID NOs: 97, 101 and 103, respectively, and a VL comprising a CDR-L1, a CDR-L2 and a CDR-L3 sequences set forth in SEQ ID NOS: 105, 107 and 108, respectively; a VH comprising a CDR-H1, a CDR-H2 and a CDR-H3 sequences set forth in SEQ ID NOs: 96, 100 and 103, respectively, and a VL comprising a CDR-L1, a CDR-L2 and a CDR-L3 sequences set forth in SEQ ID NOs: 105, 107 and 108, respectively;
a VH comprising a CDR-H1, a CDR-H2 and a CDR-H3 sequences set forth in SEQ ID
NOs: 95, 99 and 103, respectively, and a VL comprising a CDR-L1, a CDR-L2 and a CDR-L3 sequences set forth in SEQ ID NOs: 105, 107 and 108, respectively; and/or a VH comprising a CDR-H1, a CDR-H2 and a CDR-H3 sequences set forth in SEQ ID
NOs: 94, 98 and 102, respectively, and a VL comprising a CDR-L1, a CDR-L2 and a CDR-L3 sequences set forth in SEQ ID NOs: 104, 106 and 108, respectively.
The extracellular antigen binding domain may comprise the amino acid sequence of SEQ ID NO: 114 or an amino acid sequence having at least 90% sequence identity to the amino acid sequence of SEQ ID NO: 114 or may comprise the SEQ ID NO: 19.
The teachings of Albertson et al. and Oliai et al. were presented supra and they were silent about the extracellular domain having the structures instantly claimed.
Brent et al. disclosed methods and compositions for treating multiple myeloma. It
relates to chimeric antigen receptors (CARs) that specifically target B cell maturation antigen (BMCA), and immunoresponsive cells comprising such CARs. The disclosed BMCA- specific CARs have enhanced immune-activating properties, including anti-tumor activity (abstract).
The sequences claimed in the instant claims are identical with the sequences SEQ ID NOs; 53, 54 and 85 of the reference.
It would have been obvious for person of ordinary skill in the art at the time that the invention was filed to have used the antibody sequences of Brent et al. in the methods of Albertson et al. and Oliai et al. with a reasonable expectation of success since a skilled artisan would have used known and tested reagents to solve an existing problem. A person of ordinary skill in the art is always motivated to pursue the known options within her or his technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Claims 48, 49 and 60 is rejected under 35 U.S.C. 103 as being unpatentable over Albertson T. (WO2018223101-cited by Applicant) in view of Oliai et al. (cited supra) and in further view of Ports et al. (WO2018204427).
The claim adds the limitation that the BCMA targeted CAR comprises the
sequence set forth in SEQ ID NO: 19 or SEQ ID NO: 312.
The teachings of Albertson et al. and Oliai et al. were presented supra and they were silent about the extracellular domain having the structures instantly claimed.
Ports et al. teaches methods, compositions and uses involving immunotherapies, such as adoptive cell therapy, e.g., T cell therapy (abstract). One of the chimeric antigen receptors disclosed One of the recombinant receptor includes an antigen-binding domain specific for a B cell maturation antigen (BCMA) ([0034]). The sequences claimed in the instant claims are identical to the sequences SEQ ID NOs: 160 and 152 (respectively) of the reference.
It would have been obvious for person of ordinary skill in the art at the time that the invention was filed to have used the antibody sequences of Ports et al et al. in the methods of Albertson et al. and Oliai et al. with a reasonable expectation of success since a skilled artisan would have used known and tested reagents to solve an existing problem. A person of ordinary skill in the art is always motivated to pursue the known options within her or his technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Claim 51 are rejected under 35 U.S.C. 103 as being unpatentable over Albertson T. (WO2018223101-cited by Applicant) in view of Oliai et al. (cited supra) and in further view of Kalled et al. (WO2010104949 -cited by Applicant).
The claims adds the limitation that the extracellular antigen-binding domain comprises: a variable heavy chain (VH) comprising a heavy chain complementarity determining region 1 (CDR-H1), a heavy chain complementarity determining region 2 (CDR-H2) and a heavy chain complementarity determining region 3 (CDR-H3) contained within the sequence set forth in SEQ ID NO: 125 and a variable light chain (VL) comprising a light chain complementarity determining region 1 (CDR-L1), a light chain complementarity determining region 2 (CDR-L2) and a light chain complementarity determining region 3 (CDR-L3) contained within the sequence set forth in SEQ ID NO: 127; or a VH comprising a CDR-Hl, a CDR-H2 and a CDR-H3 sequences set forth in SEQ ID NOs: 260, 261, and 262, respectively, and a VL comprising a CDR-L1, a CDR-L2 and a CDR-L3 sequences set forth in SEQ ID NOs: 257, 258, and 259, respectively.
The teachings of Albertson et al. and Oliai et al. were presented supra and they were silent aboth the extracellular domain having the structures instantly claimed.
Kalled et al. disclosed antibodies that recognize the B Cell Maturation Antigen (BCMA) as well as methods for treating B cell-related disorders, including lymphomas and autoimmune diseases (Abstract).
The sequences claimed in the instant claims are identical with the sequences SEQ ID NOs: 3, 4, and 28 of the reference.
It would have been obvious for person of ordinary skill in the art at the time that the invention was filed to have used the antibody sequences of Kalled et al. in the methods of Albertson et al. and Oliai et al. with a reasonable expectation of success since a skilled artisan would have used known and tested reagents to solve an existing problem. A person of ordinary skill in the art is always motivated to pursue the known options within her or his technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Claim 53 are rejected under 35 U.S.C. 103 as being unpatentable over Albertson T. (WO2018223101-cited by Applicant) in view of Oliai et al. (cited supra) and in further view of Chaudhary et al. (WO2019232503 -cited by Applicant).
The claim adds the limitation that the extracellular antigen binding domain comprises the amino acid sequence of SEQ ID NO: 128 or an amino acid sequence
having at least 90%sequence identity to the amino acid sequence of SEQ ID NO: 128.
The teachings of Albertson et al. and Oliai et al. were presented supra and they were silent aboth the extracellular domain having the structures instantly claimed.
The reference teaches diverse antigen binding domains an platforms for construction of the next generation of chimeric antigen receptor for use in adoptive T cell therapies (abstract). SEQ ID NO: 4526 represents one of the extracellular binding domains and is identical to SEQ ID NO: 128 claimed instantly.
It would have been obvious for person of ordinary skill in the art at the time that the invention was filed to have used the antibody sequences of Kalled et al. in the methods of Albertson et al. and Oliai et al. with a reasonable expectation of success since a skilled artisan would have used known and tested reagents to solve an existing problem. A person of ordinary skill in the art is always motivated to pursue the known options within her or his technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.
Conclusion
No claims are allowed.
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ELLY-GERALD STOICA
Primary Examiner
Art Unit 1647
/Elly-Gerald Stoica/Primary Examiner, Art Unit 1647