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 .
Claims 1-30 are pending and examined on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 120, 119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed applications, Application Nos.62/066,279, 62/162,648, 62/168,710, 62/215,732, 14/918,451, or 16/667,564, fail to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application.
Instant claim 1 requires that the first dose of CAR T cells from
1 X 106 to 1 X 108 cells per kg;
1 X 106 to 1 X 107 cells/M2, or
5 X 107 to 5 X 108 cells.
All of 62/066,279, 62/162,648, 62/168,710, 62/215,732, 14/918,451, or 16/667,564 provide a description of the first dose as
no more than 1 X 106 cells/kg;
no more than 108 cells/m2, or
no more than 108 cells.
This fails to provide written description support for
(i)1 X 106 to 1 X 108 cells per kg
(ii) 1 X 106 to 1 X 107 cells/M2, or
(iii) 5 X 107 to 5 X 108 cells.
Thus, the instant claims will be considered to have the effective filing date of 3/22/2023.
Specification
(A)The specification is objected to for claiming that the instant application isa CON of U.S. patent application Ser. No. 16/667,564, filed Oct. 29, 2019, which claims priority to U.S. patent application Ser. No. 14/918,451, filed Oct. 20, 2015, which claims priority to U.S. provisional application No. 62/066,279 filed Oct. 20, 2014, which claims priority to U.S. provisional application No. 62/162,647, filed May 15, 2015, U.S. provisional application No. 62/168,710, filed May 29, 2015, and U.S. provisional application No. 62/215,732, filed Sep. 8, 2015, entitled because none of the prior applications provide a written description of what is now claimed.
(B)The specification is objected to as failing to provide proper antecedent basis for the claimed subject matter. See 37 CFR 1.75(d)(1) and MPEP § 608.01(o). Correction of the following is required: amendment of the specification to incorporate the limitations of claim 1 wherein the first dose is from 1 X 106 to 1 X 108 cells per kg; 1 X 106 to 1 X 107 cells/M2, or 5 X 107 to 5 X 108 cells.
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.
Claims 2, 3, 10 and 21 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.
(A)Claims 3 and 10 are vague and indefinite in the recitation of “substantially identical” and “substantially similar” respectively. It is unclear how much deviation is tolerated within the confines of being substantially similar or substantially identical.
(B)Claim 21 is vague and indefinite in the recitation of “suspected of exhibiting morphological disease” and “suspected of exhibiting minimum residual disease” because the threshold for suspecting that a subject harbors morphologic disease or MRS is subjective and dependent on the routineer.
(C)It is unclear if the disease or condition that persists is morphological disease, minimal residual disease or detectable molecular disease For purpose of examination, all alternatives will be considered.
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.
Claim 2 is 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.
Claim 2 requires a subject in which the disease or condition persists in said subject following administration of the first dose. The requirement of “persists” encompasses both morphological disease, minimal residual disease or detectable molecular disease
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1-3, 5-11, 14-19, 22-29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Maloney et al (WO2019/200347).
Maloney et al disclose a method of treating solid cancer and hematological malignancies including acute lymphoblastic leukemia (abstract), non-Hodgkin’s lymphomas , B-cell malignancy, leukemia, lymphoma, (page 46, lines 28-31) comprising the administration of a first dose of CAR-T cells followed by a second dose of CAR-T cells, wherein the first dose comprises about 1 X 106 of modified T cells/kg or 3.3 X 106 of modified T cells/kg (claims 2 and 3 of ‘347), and wherein the modified T cell comprises a binding protein that specifically binds to a ROR1 antigen, an intracellular component comprising an all or a portion of a 4-1BB signaling domain and all or a portion of a CD3 zeta signaling domain, and a transmembrane domain comprising all or a portion of a CD8 transmembrane domain (claim 1 of ‘347 and Figure 1) which meets the limitations of instant claim 1(i) for a first dose of a CAR-T cell from 1 X 106 to 1 X 108 cells/kg, wherein (ii) the CAR binds to an antigen expressed by a cell or tissue associated with the disease or condition and claim 11 for the first dose of cells at 1 X 106 cells/kg to 1 X 108 cells/kg; and claims 28 and 29 for intracellular signaling domains comprising 4-1BB and CD3zeta and claim 30 for a CD8 transmembrane domain and a CD3zeta signaling domain; the disease or condition is a tumor or cancer in claim 14, B-cell malignancy, leukemia or lymphoma, lymphoblastic leukemia or NHL in claims 14-17, wherein the antigen is ROR1 in claim 18. Maloney et al disclose that the composition administered in the first and second dose or subsequent doses may be the same, or different in terms of cellular concentration or the CD4+ or CD8+ type of modified T-cells (page 53, lines 8-10),thus fulfilling the limitation of; targeting the same antigen as the CAR of the first dose in claim 5; the consecutive dose being identical to the CAR expressed by cells in the first dose in claim 3; the consecutive dose comprising the same or substantially the same number of cells as the first dose in claim 10; Maloney et al disclose that in some embodiments, a second dose comprises the same amount of modified T-cell as the first dose (page 53, lines 17-19) which meets the limitation of claim 10; a second dose comprises a reduced amount of modified T cell relative to the first dose (page 53, lines 19-21) and in some embodiments the second dose comprises an increased amount of modified immune cell relative to the first dose (page 53, lines 22-23) .
. Maloney et al disclose that the modified T cells of the invention can be autologous or allogeneic (page 33, lines 25-27) which meets the limitations of claims 6-9. .
Maloney et al disclose the administration of a lymphodepleting therapy following the administration of the first dose of modified T cells and prior to the administration of the second dose of modified T cells (claim 23 of ‘347) wherein the in a preferred embodiment, lymphodepleting therapy includes cyclophosphamide and fludarabine (page 40, lines 27-29) which meets the limitations of claims 22 and 23 for administration prior to the administration of the consecutive dose, and claims 24-27 for the combination of cyclophosphamide and fludarabine.
Claims 1-are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Gilbert (U.S. 10,507,219, reference of the IDS filed 6/6/2023).
Gilbert discloses a method of treating a hematologic cancer comprising the admisntration of a consecutive dose of CAR-T cells expressing a CAR that binds to CD19 to a subject that had been previously administered a first dose of a CAR that binds CD19, said first dose comprising (i) no more than 106 of CR-expressing cells per kg which meets the limitations of claim 1 and 11, no more than 108 CAR expressing cells, which meets the limitation in claims 1 and 13, and no more than 108 CAR expressing cells/m2 (claim 1 of ‘219) wherein no more than 108 CAR expressing cells/m2 includes 2×106, 5×106, 1×107 cells per m2 of the subject (column 29, lines 9-10) which meets the limitations of claims 1 and 12. The CAR that binds to CD19 meets the limitation of claim 1, section (ii) and claim 18. Gilbert discloses that the CAR expressed by cells in the second dose contains the same antigen-binding domain (claim 5 of ‘219) which meets the limitation of claims 3 and 5. Gilbert discloses that the first and second doses of cells is sufficient for reduction on burden of the hematological malignancy in the subject and/or the administration of the consecutive dose leas to a reduction in burden of the hematological malignancy in the subject (claim 6 of ‘219) which meets the limitation of claim 2 wherein the disease or condition persists following administration of the first dose. Gilbert discloses that at the time prior to initiation of admisntration of the consecutive dose, the subject exhibits morphological disease, the consecutive dose comprising less than, or about the same number of CAR expressing cells as in the first dose; and at the time prior to the initiation of the consecutive dose, the subject exhibits minimal residual disease, then the consecutive dose comprises an increased number of CAR expressing cells relative to the first dose. (claim 7 of ‘219) which meets the limitation of instant claims 10, 19-21, Gilbert discloses the administration of the chemotherapeutic agent comprising the combination of cyclophosphamide and fludarabine prior to the administration of the consecutive dose (claims 11-16) which meets the limitations of claims 22-27. Gilbert discloses that the hematological malignancy being treated is ALL, CLL or NHL (claims 19 and 20 of ‘219) including indolent B cell lymphomas and B-cell malignancies (column 21, line 51) which meets the limitation of instant claims 14-17. Gilbert disclose that the CAR expressed in the consecutive dose is identical to the CAR expressed by cell in the first dose (claim 39 of ‘219) which meets the limitation of instant claims 3 and 5. Gilbert disclose that the CAR T cells have been derived from the subject to which they are to be administered. Or alternatively, the CAR-T cells are allogeneic (column 12, lines 17-20) which meets the limitations of claims 6-9. Gilbert discloses an embodiment wherein the intracellular signaling component of the CAR comprises a 4-1BB costimulatory domain linked to a CD3 zeta intracellular domain (column 53, lines 1-3) which meets the limitations of claims 28 and 29 and that limitation in claim 30. Gilbert discloses that the transmembrane domain is derived from CD8 alpha which meets that limitation in claim 30. Gilbert discloses that in some embodiments, the CAR expressed by cells of the consecutive dose is substantially identical to the CAR expressed by cells in the first dose, which meets the limitations of claim 4 wherein the CAR expressed by cels of the consecutive dose is different from the CAR expressed by cell of the first dose because “substantially identical” is different.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-11, 14-19, 22-29 are rejected under 35 U.S.C. 103 as being unpatentable over Maloney et al (WO2019/200347).
Maloney et al teach the specific embodiments of claims 1-3, 5-11, 14-19, 22-29 for the reasons set forth above. Maloney et al do not specifically teach that the CAR expressed by the cell in the consecutive dose is different to the CAR expressed by the cells of the first dose..
Maloney et al does not specifically teach that compositions administered in the first and second doses or subsequent doses may be different (page 53, lines 8-10).
Maloney et al teach embodiments wherein the tumor associated antigen is ROR1 (page 19, line 7). Maloney et al teach particular embodiments, the binding protein comprises a binding domain derived from antibody R12, antibody 2A2, antibody Rl 1, antibody ETC-961, antibody D10, or antibody H10, which are all the ROR1 antibodies (page 19, lines 7-10).
It would have been prima facie obvious at the time of the effective filing date to substitute an alternate ROR1 binding CAR T cell for the cells of the second or subsequent dose. One of skill in the art would have been motivated to do so because said antibodies are art-recognized equivalents for the binding of ROR1.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-3, 5, 10-22 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of U.S. Patent No.10,507,219. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patent anticipate the instant claims. Claims 1-4 and 31 of ‘219 anticipate instant claims 1 and 18..Claim 5 anticipates instant claims 3 and 5. Claim 6 anticipates instant claim 2 because a “reduction in burden” is commensurate with the persistence of the disease after administration of the first dose. Claim 7 anticipate instant claims 19-21. Claims 11-16 anticipate instant claims 22-27. Claims 19-20, 33 and 34 anticipate instant claims 16 and 17. The claims of ‘219 do not specifically teach that 108 cells/m2 encompasses 1 X 106 cells/m2 to 1 X 107 cells/m2, or that the hematological malignancies being treated is a B-cell malignancy.
Section M.P.E.P. 804 IIb
The specification can be used as a dictionary to learn the meaning of a term in the patent claim.
In the instant case, the ‘219 specification defines leukemia or lymphoma as including:
chronic lymphocytic leukemia (CLL), ALL, non-Hodgkin's lymphoma, acute myeloid leukemia, multiple myeloma, refractory follicular lymphoma, mantle cell lymphoma, indolent B cell lymphoma, B cell malignancies
Thus, instant claim 15 is an obvious variant of the leukemia or lymphoma of claim 19 of ‘219.
Further, the ‘219 specification defines no more than 1 X 108 cells/M2 as including
no more than 2×10.6, 5×106, 1×107 cells per m2 of the subject.
Thus, instant claim 12 is an obvious variant of “no more than about 1 X 108 cells/m2” in claims 1 and 31 of ‘219.
Claims 1-3, 5, 10-22 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-43 of U.S. Patent No.11,633,426. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patent anticipate the instant claims.
Claims 1, 2 and 26 of the patent anticipates instant claims 1, 11, 13 and 18. Claims 5 and 30 anticipate instant claim 5. Claims 6 and 31 of the patent anticipates instant claim 3. Claim 7 of the patent anticipates instant claim 2 because a reduction in burden of the malignancy is commensurate with persistence of the disease after the first dose. Claims 8 and 9 of the patent anticipates instant claims 19-21. Claims 12-17 and 34-37 anticipate instant claims 22-27. Claims 21, 22, 40 and 41 of ‘426 anticipates claims 16 and 17.
The claims of ‘426 do not specifically teach that 108 cells/m2 encompasses 1 X 106 cells/m2 to 1 X 107 cells/m2, or that the hematological malignancies being treated is a B-cell malignancy.
Section M.P.E.P. 804 IIb
The specification can be used as a dictionary to learn the meaning of a term in the patent claim.
In the instant case, the ‘426 specification defines leukemia or lymphoma as including:
chronic lymphocytic leukemia (CLL), ALL, non-Hodgkin's lymphoma, acute myeloid leukemia, multiple myeloma, refractory follicular lymphoma, mantle cell lymphoma, indolent B cell lymphoma, B cell malignancies
Thus, instant claim 15 is an obvious variant of the leukemia or lymphoma of claims 121 and 40 of ‘426.
Further, the ‘426 specification defines no more than 1 X 108 cells/M2 as including
no more than 2×10.6, 5×106, 1×107 cells per m2 of the subject.
Thus, instant claim 12 is an obvious variant of “no more than about 1 X 108 cells/m2” in claims 1 and 26 of ‘426..
All claims are rejected.
.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KAREN A CANELLA whose telephone number is (571)272-0828. The examiner can normally be reached M-F 10-6:30.
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KAREN A. CANELLA
Examiner
Art Unit 1643
/Karen A. Canella/Primary Examiner, Art Unit 1643
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