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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 27 April 2026 has been entered.
Claim Status
Claims 2-8, 12-13, 31, and 39 are cancelled. Claims 1, 9-11, 14-30, 32-38, and 40-44 as filed on 27 April 2026 are pending. Claims 18-28 are withdrawn. Claims 1, 9-11, 14-17, 29-30, 32-38, and 40-44 are under examination.
Rejections Withdrawn
Rejection of claims 1, 14, 16-17, 23, and 29-42 under 35 U.S.C. 103 is withdrawn with applicant amendment of claims and new search and examination.
Applicant’s arguments with respect to claims 1, 14, 16-17, 23, and 29-42 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1, 9, 16, and 43 are rejected under 35 U.S.C. 103 as being unpatentable over O’Hear et. al. Haematologica. 100(3):336-344. (2015) (PTO-892), Sadelain et. al. Cancer Discov. 3(4):388-398. 2013 (PTO-892), and Vallera (WO2017062604-A1) (PTO-892).
Regarding claims 1 and 43, O’Hear teaches anti-CD33 chimeric antigen receptors (CARs) for use in treatment of acute myeloid leukemia (AML) (abstract) where the CARs comprise a CD33 binding scFv, a hinge, a transmembrane domain, a co-stimulatory domain, and a CD3 zeta domain (Figure 1 A) and further teaches the intracellular domain can be CD28 or 4-1BB (page 337 in col 1 in lines 10-15).
O’Hear does not teach instant CD33 binding scFv comprising first a VH of instant SEQ ID NO: 15, a linker, and a VL of instant SEQ ID NO: 16 and the entire scFV is shown in amino acids 22 to 263 of instant SEQ ID NO: 23.
This deficiency is filled by Sadelin and Vallera.
Vallera teaches a CD33 binding of instant SEQ ID NO: 23 which comprises instant SEQ ID NO: 15 and 16 in that order in SEQ ID NO: 2. Vallera teaches the use of binding domains in CARs but teaches the risk of cytokine toxicity and lack of long term persistence of CARs (page 31 in lines 22-30). Valera teaches the use of its fusions for use in treatment of AML (page 11 in lines 16-21 and page 12 in lines 13-16).
Sadelin teaches CARs that provide antigen-binding and T-cell activating functions where the antigens target tumor antigens (abstract). Sadelin teaches CD33 binding CARs that comprise an scFv, 41BB or CD28 costimulatory domains, and CD3 zeta domains for use in acute lymphoblastic leukemia (Table 1). Sadelin teaches first, second, and third generation CARs that comprise varying versions of the component domains including CD28 transmembrane domains for use with varying co-stimulatory domains and scFvs (Figure 1). Sadelin teaches the costimulatory ligands enhance T-cell proliferation and cytokine release for improved therapeutic function (page 392 in col 2 in par 2 and page 396 in col 1 in last 3 lines).
Regarding claim 16, Sadelin teaches the CARs comprise a spacer (figure 1).
It would have been obvious at the time the application was filed to substitute the scFv of the CD33 binding CAR of O’Hear with the scFv of Vallera producing a CD33 binding CAR comprising an scFv of SEQ ID NO: 15 and 16 from N-terminus to C-terminus, a hinge, a transmembrane domain, a CD28 co-stimulatory domain, and a CD3 zeta intracellular domain. The substitution of art equivalent CD33 binding scFvs used for treatment of AML would be prima facie obvious (see MPEP 2183). Further, one of skill in the art would have been motivated to produce novel CD33 binding CAR T cells and would use known in the art scFvs for this purpose, O’Hear teaches the use of different scFvs that bind tumor antigens in their CARs, Vallera teaches away from CARs but cites risk of cytokine toxicity and lack of long term persistence of CARs, but Sadelin teaches improvements in CAR development results in the costimulatory ligands enhance T-cell proliferation and cytokine release for improved therapeutic function. There would have been a reasonable expectation of success as O’Hear and Sadelin both teach the mixing and matching of scFvs and other components of CARs, specifically teach overcoming the concerns of Vallera regarding use of their binding domains in CARs, and O’Hear, Sadelin, and Vallera all tach the use of scFv domains that bind CD33 in the same patient population of AML.
Claims 1, 14, 23, 30, 32, 34, 38, 40, and 42-44 are rejected under 35 U.S.C. 103 as being unpatentable over O’Hear et. al. Haematologica. 100(3):336-344. (2015) (PTO-892), Sadelain et. al. Cancer Discov. 3(4):388-398. 2013 (PTO-892), and Vallera (WO2017062604-A1) (PTO-892) as applied to claims 1, 9, 16, and 43 above, and further in view of (JP 2017522880 A) (“JP” PTO-892).
Applicant’s elected species is the CAR of instant SEQ ID NO: 23 which comprises the amino acids 1 to 21 of MALPVTALLLPLALLLHAARP, which is a CD8α signal peptide, followed by the scFv from amino acids 22-263, followed by the Ser-Gly spacer, CD28 hinge of SEQ ID NO: 10 from amino acids 266 to 307, a CD28 transmembrane domain of SEQ ID NO: 11 from amino acids 308 to 375, and a CD3 zeta domain of SEQ ID NO: 9 from amino acids 376 to 487.
The teachings of O’Hear from the previous rejection under 35 U.S.C. 103 are incorporated here in full.
O’Hear teaches the CARs of the invention are for use in therapeutics to be administered to patients (abstract and Figure 5).
The teachings of Sadelin and Vallera from the previous rejection under 35 U.S.C. 103 are incorporated here in full.
O’Hear teaches a CD8 leader sequence with a CD33 scFv and a CD3 zeta domain and in view of Sadelin and Vallera it teaches a CAR comprising a CD8 leader sequence, the CD33 scFv binding domain of the instant claims and elected by applicant, a spacer, a hinge, a CD28 co-stimulatory domain, and a CD3 zeta domain.
O’Hear in view of Sadelin and Vallera does not teach the specific sequences of the CD8 leader sequence of amino acids MALPVTALLLPLALLLHAARP, the spacer of Ser-Gly, the CD28 intracellular domain comprising amino acids RSKRSRLLHSDYMNMTPRRPGPTRKHYQPYAPPRDFAAYRS as required by claim 34, and the CD3 zeta domain of instant SEQ ID NO: 9, or the pharmaceutical compositions comprising a carrier.
These deficiencies are filled by JP.
JP teaches CD33 binding CARs that comprise the CD8α leader sequence that match amino acids 1 to 21 of instant SEQ ID NO: 23 (abstract and SEQ ID NO: 1 page 27 in par 1).
JP further teaches the CD3 zeta domain for use in the CD33 binding CAR of SEQ ID NO: 9 which matches instant SEQ ID NO: 9 and the domain in instant SEQ ID NO: 23 (page 27 in par 7), as required by instant claim 32.
JP further teaches an effective linker for the scFv of Ser-Gly (page 25 in par 5).
Regarding the unelected CD8 hinge of instant SEQ ID NO: 6 of instant claim 6, JP teaches SEQ ID NO: 2 which matches instant SEQ ID NO: 6 (page 27 in par 2).
JP teaches CD28 intracellular domain of SEQ ID NO: 379 which matches the requirement of amino acids of instant claim 34 which is a functional portion as required by instant claim 30 (page 27 in par 5).
Regarding claims 23, 38, 40, 42, and 44, JP teaches pharmaceutical compositions comprise therapeutic CAR expressing cells of the invention with carriers that are physiologically suitable for administration to a patient (page 69 in par 9).
Regarding the leader sequence of the CAR of instant SEQ ID NO: 23, it would have been obvious at the time the application was filed to substitute the generic CD8 leader sequence of O’Hear with the CD8α leader sequence JP teaches as part of a CD33 binding CAR. It would have been prima facie obvious to substitute the generic CD8 leader for an art equivalent CD8α sequence of MALPVTALLLPLALLLHAARP (see MPEP 2183). There would have been a reasonable expectation of success as O’Hear and JP are both teaching CD33 binding CARs for use in therapeutics and the activity of CD8 leader sequences were well known in the art.
Regarding the spacer sequence of Ser-Gly, it would have been obvious at the time the application was filed to combine the domains of the CD33 binding CAR comprising a spacer between the scFv and the hinge of O’Hear in view of Sadelin and Vallera with the specific spacer of Ser-Gly taught by JP. It would have been prima facie obvious to substitute the generic spacer for an art equivalent spacer of Ser-Gly that JP teaches (see MPEP 2183). There would have been a reasonable expectation of success as JP teaches the spacer that connects a CD33 binding ScFv to a hinge in a CAR.
Regarding the CD8 hinge of instant SEQ ID NO: 6, it would have been obvious at the time the application was filed to substitute the generic hinge of the CAR present in the CD33 binding CARs of O’Hear with the CD8 hinge of JP which matches instant SEQ ID NO: 6. It would have been prima facie obvious to substitute the generic hinge of O’Hear for an art equivalent CD8 hinge of JP that matches the instant sequences (see MPEP 2183). There would have been a reasonable expectation of success as O’Hear and JP both teach a CD33 binding CAR comprising a hinge for use in a therapeutic CAR.
Regarding CD3 zeta of instant SEQ ID NO: 9, it would have been obvious at the time the application was filed to substitute the generic CD3 zeta domain of the CAR present in the CD33 binding CARs of O’Hear with the CD3 zeta domain of JP which matches instant SEQ ID NO: 9. It would have been prima facie obvious to substitute the generic CD3 zeta domain of O’Hear for an art equivalent CD3 zeta of JP that matches the instant sequences (see MPEP 2183). There would have been a reasonable expectation of success as O’Hear and JP both teach a CD33 binding CAR comprising a CD3 zeta domain for use in a therapeutic CAR.
Regarding claims 23, 38, 40, 42, and 44, it would have been prima facie obvious to substitute the generic pharmaceutical composition of O’Hear with the specifics of a composition comprising carriers taught by JP (see MPEP 2183).
Claims 1, 11, 14-15, 35, and 41 are rejected under 35 U.S.C. 103 as being unpatentable over O’Hear et. al. Haematologica. 100(3):336-344. (2015) (PTO-892), Sadelain et. al. Cancer Discov. 3(4):388-398. 2013 (PTO-892), and Vallera (WO2017062604-A1) (PTO-892) as applied to claims 1, 9, 16, and 43 as applied to claims 1, 9, 16, and 43 above, and further in view of Hong (WO 2017015634 A2) (PTO-892).
Applicant’s elected species is the CAR of instant SEQ ID NO: 23 which comprises the amino acids 1 to 21 of MALPVTALLLPLALLLHAARP, which is a CD8α signal peptide, followed by the scFv from amino acids 22-263, followed by the Ser-Gly spacer, CD28 hinge of SEQ ID NO: 10 from amino acids 266 to 307, a CD28 transmembrane domain of SEQ ID NO: 11 from amino acids 308 to 375, and a CD3 zeta domain of SEQ ID NO: 9 from amino acids 376 to 487.
The teachings of O’Hear from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
O’Hear teaches the CARs of the invention are for use in therapeutics to be administered to patients (abstract and Figure 5).
The teachings of Sadelin and Vallera from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
O’Hear teaches a CD8 leader sequence with a CD33 scFv and a CD3 zeta domain and in view of Sadelin and Vallera it teaches a CAR comprising a CD8 leader sequence, the CD33 scFv binding domain of the instant claims and elected by applicant, a spacer, a hinge, a CD28 co-stimulatory domain, and a CD3 zeta domain.
O’Hear in view of Sadelin and Vallera does not teach the CD28 hinge of instant SEQ ID NO: 10 or the pharmaceutical compositions comprising a carrier.
These deficiencies are filled by Hong.
Regarding claims 11 and 14-15, Hong teaches a CD28 hinge of instant SEQ ID NO: 10 in SEQ ID NO: 177 ([0582]).
Regarding claims 35 and 41, Hong teaches pharmaceutical compositions comprising the CAR in a T cell and acceptable carriers for suitable compositions for use in patients ([0429]-[0430]).
It would have been obvious at the time the application was filed to substitute the hinge of O’Hear with the CD28 hinge sequence taught by Hong as part of a CAR. It would have been obvious to substitute art equivalent hinges that have the same activity in a CAR (see MPEP 2183). There would have been a reasonable expectation of success as Hong teaches hinges for use in pharmaceutical CARs.
Regarding claims 35 and 41, it would have been prima facie obvious to substitute the generic pharmaceutical composition of O’Hear with the specifics of a composition comprising carriers taught by Hong (see MPEP 2183).
Claims 1 and 10 are rejected under 35 U.S.C. 103 as being unpatentable over O’Hear et. al. Haematologica. 100(3):336-344. (2015) (PTO-892), Sadelain et. al. Cancer Discov. 3(4):388-398. 2013 (PTO-892), and Vallera (WO2017062604-A1) (PTO-892) as applied to claims 1, 9, 16, and 43 as applied to claims 1, 9, 16, and 43 above, and further in view of Bondanza (CN 107074930 A) (PTO-892).
Applicant’s elected species is the CAR of instant SEQ ID NO: 23 which comprises the amino acids 1 to 21 of MALPVTALLLPLALLLHAARP, which is a CD8α signal peptide, followed by the scFv from amino acids 22-263, followed by the Ser-Gly spacer, CD28 hinge of SEQ ID NO: 10 from amino acids 266 to 307, a CD28 transmembrane domain of SEQ ID NO: 11 from amino acids 308 to 375, and a CD3 zeta domain of SEQ ID NO: 9 from amino acids 376 to 487.
The teachings of O’Hear from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
O’Hear teaches the CARs of the invention are for use in therapeutics to be administered to patients (abstract and Figure 5).
The teachings of Sadelin and Vallera from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
O’Hear teaches a CD8 leader sequence with a CD33 scFv and a CD3 zeta domain and in view of Sadelin and Vallera it teaches a CAR comprising a CD8 leader sequence, the CD33 scFv binding domain of the instant claims and elected by applicant, a spacer, a hinge, a CD28 co-stimulatory domain, and a CD3 zeta domain.
O’Hear in view of Sadelin and Vallera does not teach the CD28 transmembrane domain of instant SEQ ID NO: 11.
This deficiency is filled by Bondanza.
Bondanza teaches CARs that can bind carrying antigens based on the scFv including CD33 (abstract and page 5 in par 14)and a CD28 transmembrane domain of SEQ ID NO: 18 which matches instant SEQ ID NO: 11 (page 6 in pars 8-9).
It would have been obvious at the time the application was filed to substitute the generic transmembrane domain of O’Hear in view of Sadelin with the CD28 transmembrane sequence taught by Bondanza as part of a CD33 binding CAR. It would have been obvious to substitute art equivalent hinges that have the same activity in a CAR (see MPEP 2183). There would have been a reasonable expectation of success as Bondanza teaches hinges for use in CD33 binding CARs.
Claims 1, 17, 29, 33, and 36-37are rejected under 35 U.S.C. 103 as being unpatentable over O’Hear et. al. Haematologica. 100(3):336-344. (2015) (PTO-892), Sadelain et. al. Cancer Discov. 3(4):388-398. 2013 (PTO-892), Vallera (WO2017062604-A1) (PTO-892), (JP 2017522880 A) (“JP” PTO-892), Hong (WO 2017015634 A2) (PTO-892), and Bondanza (CN 107074930 A) (PTO-892).
Applicant’s elected species is the CAR of instant SEQ ID NO: 23 which comprises the amino acids 1 to 21 of MALPVTALLLPLALLLHAARP, which is a CD8α signal peptide, followed by the scFv from amino acids 22-263, followed by the Ser-Gly spacer, CD28 hinge of SEQ ID NO: 10 from amino acids 266 to 307, a CD28 transmembrane domain of SEQ ID NO: 11 from amino acids 308 to 375, and a CD3 zeta domain of SEQ ID NO: 9 from amino acids 376 to 487.
The teachings of O’Hear from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
O’Hear teaches anti-CD33 chimeric antigen receptors (CARs) for use in treatment of acute myeloid leukemia (AML) (abstract) where the CARs comprise a CD33 binding scFv, a hinge, a transmembrane domain, a co-stimulatory domain, and a CD3 zeta domain (Figure 1 A) and further teaches the intracellular domain can be CD28 or 4-1BB (page 337 in col 1 in lines 10-15).
O’Hear teaches the CARs of the invention are for use in therapeutics to be administered to patients (abstract and Figure 5).
O’Hear does not teach the sequences required by instant SEQ ID NO: 23.
These deficiencies are filled by Sadelin, Vallera, JP, Hong, and Bondanza.
The teachings of Sadelin, Vallera, JP, and Bondanza from the previous rejections under 35 U.S.C. 103 are incorporated here in full.
O’Hear in view of Sadelin, Valeera, Hong, and JP teaches a CD33 binding CAR comprising amino acids 1 to 265 and 376 to 487 of instant SEQ ID NO: 23 as previously explained in the previous art rejections.
O’Hear in view of Hong teaches instant SEQ ID NO: 10 which are amino acids 266 to 307 of instant SEQ ID NO: 23.
O’Hear in view of Bondanza teaches instant SEQ ID NO: 11 which are amino acids 308 to 375 of instant SEQ ID NO: 23.
It would have been obvious at the time the application was filed to substitute the components of the CD33 binding CAR of O’Hear with the components of Sadelin, Vallera, JP, Hong, and Bondanza to produce the CAR of instant SEQ ID NO: 23. The substitutions of the components of the CAR of O’Hear with art equivalents of Sadelin, Vallera, JP, Hong, and Bondanza would be prima facie obvious as the leader sequence, scFv, hinge, transmembrane domain, costimulatory domain, and CD3 zeta domains used in CARs are art equivalents used for the same biological purpose (see MPEP 2183). One of skill in the art would have further been motivated by the teachings of O’Hear, Sadelin, and Bodanza all teach the substitution of CAR domains explicitly varying scFvs, hinges, transmembrane domains, and signaling domains producing working CARs that are effective therapeutics. There would have been a reasonable expectation of success as they are substitutions of domains with the same biological functions and O’Hear, Sadelin, and Bodanza all teach the successful variation in domains where therapeutic effect remains with these variations.
Regarding claims 36-37, it would have been prima facie obvious to substitute the generic pharmaceutical composition of O’Hear with the specifics of a composition comprising carriers taught by JP and Hong (see MPEP 2183).
Conclusion
No claims allowable.
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/F.E./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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