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
1. A request for continued examination under 37 CFR 1.114 was filed in this application after a decision by the Patent Trial and Appeal Board, but before the filing of a Notice of Appeal to the Court of Appeals for the Federal Circuit or the commencement of a civil action. 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examination under 37 CFR 1.114 and the fee set forth in 37 CFR 1.17(e) has been timely paid, the appeal has been withdrawn pursuant to 37 CFR 1.114 and prosecution in this application has been reopened pursuant to 37 CFR 1.114. Applicant’s submission filed on September 10, 2025 has been entered.
2. Claims 19 and 21 have been amended. Claims 9, 10, 13, 14, 18, 20, 22, and 25-31 have been cancelled. New claims 33-36 have been added. Claims 1-8, 11, 12, 15-17, 19, 21, 23, 24, and 32-36 are pending and currently being examined.
Drawings
3. The drawings are objected to because the description of Fig. 8 refers to red, blue and yellow lines. However, color drawings have not been submitted.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Rejections Maintained/Modified
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.
4. Claim(s) 19, 21, 23, 24, and 33 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/138491 A1 (Ma et al. Sep. 1, 2016, IDS), “Ma”.
Ma teaches that CD5 is expressed in T- cell lymphomas and leukemias and targeting them with chimeric antigen receptors in CD8+ T cells. See p. 2-lines 8-10, p. 22-lines 10-22, p. 33-lines 10-28, p. 38-lines 1-18 and claims 13-20.
Ma teaches using CD8 cytotoxic T cells. See p. 32-lines 15-17 and p. 48-lines 13-15.
Ma teaches that the antigen binding domain includes a scFv. See p. 23-lines 1-4.
Ma teaches that CAR can include CD3 zeta and CD28 signaling domains. See p. 25-lines 1-10 and claims 14-16 and claims 13-16 and 31-32.
Ma teaches that the T cells can be allogeneic or autologous. See p. 33-lines 5-10 and p. 34-lines 20-21.
Ma teaches additionally treating with chemotherapy. See p. 44-lines 20-25 and p. 46-lines 16-23.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Ma and use CAR T cells directed to CD5 because Ma teaches that CD5 is expressed in T cell lymphomas and targeting them with chimeric antigen receptors in allogeneic or autologous CAR T cells. One would have been motivated to use CAR T cells directed to CD5 to more effectively target cells that had a CD5+ phenotype.
In regard to the T cells lacking surface expression CD5 sufficient to cause fratricide, Ma teaches that antibody binding to CD5 results in CD5 internalization and T cells transduced either with CD5CAR or anchored CD5 scFv lentiviruses displayed essentially complete downregulation of the surface CD5 protein. See p. 69-lines 20-30 and Fig. 24B. Similarly, the instant specification teaches that CD5-CAR transduced T cells exhibited loss of CD5 expression, which limited fratricide. See Example 2, ¶¶ [0160-0161], and Fig 1A-D. Thus, given that Ma and the instant specification teach that a CD5CAR or anti-CD5 scFv eliminated CD5 expression, the CD5CAR T cells of Ma would inherently lack surface expression CD5 sufficient to cause fratricide.
Response to Arguments
5. Applicant argues that in affirming the Examiner’s rejection of claims 19, 21, and 23-30, the Board found Applicant’s arguments on obviousness to be unpersuasive considering the claims did not recite a solution to the self-killing/fratricide problem. See Decision on Appeal dated July 28", 2025 (Appeal No. 2024-003581) at page 5-8. Claim 19 has been amended to recite that the CD5 chimeric antigen receptor (CAR) expressing immune cells lack surface expression of CD5 sufficient to cause fratricide.
Applicant argues that as the Board noted in its Decision on page 5, n. 3, the Ma Provisional is silent as to the existence of fratricide (self-killing) in CD5 CAR T cells, let alone any solution to this fratricide issue. Accordingly, there is no evidence of record to establish that one of ordinary skill in the art would have reasonably expected loss of CD5 surface expression in T cells upon expression of a CD5 CAR, let alone that any such loss of expression would be sufficient to resolve the fratricide issue.
Applicant’s arguments have been considered, but have not been found persuasive. In regard to the T cells lacking surface expression CD5 sufficient to cause fratricide, Ma teaches that antibody binding to CD5 results in CD5 internalization and T cells transduced either with CD5CAR or anchored CD5 scFv lentiviruses displayed essentially complete downregulation of the surface CD5 protein. See p. 69-lines 20-30 and Fig. 24B. Similarly, the instant specification teaches that CD5-CAR transduced T cells exhibited loss of CD5 expression, which limited fratricide. See Example 2, ¶¶ [0160-0161], and Fig 1A-D. Thus, given that Ma and the instant specification that a CD5CAR or anti-CD5 scFv eliminated CD5 expression, the CD5CAR T cells of Ma would inherently lack surface expression CD5 sufficient to cause fratricide.
Thus, the rejection is maintained for the reasons previously set forth and above.
New Claim Rejections - 35 USC § 103
6. Claim(s) 19, 21, 23, 24 and 33-36 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/138491 A1 (Ma et al. Sep. 1, 2016, IDS), “Ma” as applied to claims 19, 21, 23, 24, and 33 above, and further in view of Jena and Cooper (Blood 19 Aug. 2010, 116(7): 1035-1044), “Jena” and in view of Moritz and Groner (Gene Therapy 1995 2: 539-546), “Moritz”.
Ma teaches set forth above and additionally teaches the CARs can include a hinge region. See paragraph bridging pp. 2-3 and p. 49-lines 25-27.
Ma does not explicitly teach a spacer domain or an example of CD5CAR with a CD28 and TCR zeta chain.
Jena teaches that CAR-T cells were developed to overcome mechanisms by which tumors escape immune surveillance. Jena teaches that a CAR comprises an exodomain with an antigen binding domain, e.g., scFv, and flexible hinge and spacer region, such as from CD8a or an immunoglobulin, linked to a transmembrane domain and cytoplasmic signaling domain. See p. 1035-righ column and Fig. 1.
Jena teaches that inclusion of the signaling domains from costimulatory domains like CD28 with a CD3 zeta signaling domain produces a fully competent activation signal and improve antitumor activity. See p. 1037-left col. and Fig. 1.
Moritz teaches that hinge/spacer regions in a ErbB-2 CAR are required for binding of ErbB-2 and signaling activity. See abstract, Discussion, and Figs. 1-6.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Ma, Jena, and Moritz and make a CD5 CAR with a hinge and spacer region and with a CD3 zeta signaling domain and CD28 costimulatory domain because Jena teaches CARs comprise flexible hinge and spacer region and the combination of a CD3 zeta signaling domain and CD28 costimulatory produce a fully competent activation signal and improve antitumor activity and Moritz teaches that hinge/spacer regions in a ErbB-2 CAR are required for binding of ErbB-2 and signaling activity. Thus, given the benefits and importance of hinge/spacer region and the signaling domain with a CD3 zeta domain and a costimulatory domain like that of CD28, one would have been motivated to construct a CD5 CAR of Ma with these domains.
New 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.
7. Claim 11 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 11 recites the limitation "to the anti-CD5 scFv" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Amendment of the claim to "to an anti-CD5 scFv of the CAR" would help to obviate this rejection.
New Double Patenting Rejection
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.
8. Claims 1-8, 11, 12, 15-17, 19, 21, 23, 24, and 32-36 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 10,786,549 B2 (Mamonkin et al. Sep. 29, 2020, of record).
The ‘549 claims are drawn to:
1. As a composition of matter, immune cells that express a chimeric antigen receptor (CAR) that targets CD5, wherein the CAR comprises the amino acid sequence of SEQ ID NO:13 or SEQ ID NO:14.
2. The composition of claim 1, wherein the cells are T cells, NK cells, dendritic cells, or a mixture thereof.
3. The composition of claim 1, wherein the CAR is expressed from a recombinant polynucleotide.
4. The composition of claim 3, wherein the polynucleotide further comprises a suicide gene, a cytokine, an additional CAR, a cytokine receptor, or a chimeric cytokine receptor.
5. The composition of claim 1, wherein the immune cells comprise a polynucleotide that comprises a suicide gene, a cytokine, an additional CAR, a cytokine receptor, or a chimeric cytokine receptor, wherein said polynucleotide is a different molecule than the polynucleotide that expresses the CAR that targets CD5.
6. The composition of claim 1, wherein the CAR comprises a co-stimulatory molecule endodomain selected from the group consisting of CD28, CD27, 4-1BB, OX40, ICOS, and a combination thereof.
7. The composition of claim 1, wherein the CAR comprises a co-stimulatory molecule endodomain that is not 4-1BB.
8. The composition of claim 4, wherein the additional CAR is an activating CAR or an inhibitory CAR.
9. The composition of claim 2, wherein said T cells are CD4+ T cells.
10. The composition of claim 2, wherein said T cells are CD8+ T cells.
11. The composition of claim 2, wherein said T cells are Treg cells.
12. The composition of claim 1, wherein the CAR comprises one or more scFvs, in addition to an scFV comprised in SEQ ID NO:13 or SEQ ID NO:14.
13. The composition of claim 12, wherein the one or more scFvs in addition to the scFv comprised in SEQ ID NO:13 or SEQ ID NO:14 targets CD19, CD20, CD22, Kappa or light chain, Glypican-3, CD30, CD33, CD123, CD38, ROR1, ErbB2, ErbB3/4, EGFR VIII, carcinoembryonic antigen, EGP2, EGP40, mesothelin, TAG72, PSMA, NKG2D ligands, B7-H6, IL-13 receptor α2, IL-11 receptor R α, MUC1, MUC16, CA9, GD2, GD3, HMW-MAA, CD171, Lewis Y, G250/CAIX, HLA-AI MAGE A1, HLA-A2 NY-ESO-1, PSC1, folate receptor-α, CD44v7/8, 8H9, NCAM, VEGF receptors, 5T4, Fetal AchR, NKG2D ligands, CD44v6 or CD7.
14. The composition of claim 1, wherein the CAR comprises a transmembrane domain selected from the group consisting of CD3-zeta, CD28, CD8α, CD4, or a combination thereof.
15. The composition of claim 1, wherein the CAR comprises a spacer derived from IgG CH3 without the CH2 domain.
16. The composition of claim 1, wherein the spacer is derived from CD8α.
17. The composition of claim 1, wherein the CAR comprises amino acid sequence of SEQ ID NO:14.
18. The composition of claim 1, wherein the CAR comprises the amino acid sequence of SEQ ID NO:13.
19. The composition of claim 1, wherein the CAR comprises a CD5scFv, a leader sequence, a CH2+CH3 IgG1 spacer, a hinge, CD28 transmembrane domain, CD28 co-stimulatory endodomain, and CD3zeta.
Although the claims at issue are not identical, they are not patentably distinct from each other because the ‘549 patent discloses the utility for the anti-CD5 CAR immune cells claimed in the ‘549 patent that is now claimed in the instant claims 1-8, 11, 12, 15-17, 19, 21, 23, 24, and 32-36. See the ‘549 patent disclosure, from which the current application is a continuation.
In Sun Pharmaceutical Industries Ltd. v. Eli Lilly and Co., 95 USPQ2d 1797 (Fed. Cir. 2010) the US Court of Appeals, Federal Circuit stated at 1800:
Our prior obviousness-type double patenting decisions in Geneva and Pfizer, which addressed factual situations closely resembling that presently before the court, control this case. In both cases, we found claims of a later patent invalid for obviousness-type double patenting where an earlier patent claimed a compound, disclosing its utility in the specification, and a later patent claimed a method of using the compound for a use described in the specification of the earlier patent. See Pfizer, 518 F.3d at 1363 [Pfizer, Inc. v. Teva Pharmaceuticals USA, Inc., 518 F.3d 1353 [ 86 USPQ2d 1001] (Fed. Cir. 2008)]; Geneva, 349 F.3d at 1385-86. We held that a “claim to a method of using a composition is not patentably distinct from an earlier claim to the identical composition in a patent disclosing the identical use.” Pfizer, 518 F.3d at 1363; Geneva, 349 F.3d at 1385-86. [Geneva Pharmaceuticals, Inc. v. GlaxoSmithKline PLC, 349 F.3d 1373 [68 USPQ2d 1865] (Fed. Cir. 2003)]
Thus, the anti-CD5 CAR immune cells claimed in ‘549 patent are not distinct from the methods now claimed because the claimed method is disclosed in the ‘549 patent.
It is noted that Applicant filed a corrected Application Data Sheet on August 31, 2023 to make the instant case a Divisional of the ‘549 patent to obviate the nonstatutory double patenting rejection. However, the Office has not recognized the change in relationship to the ‘549 patent by issuing a corrected filing receipt recognizing the change. Thus, the relationship of the instant application to the ‘549 patent is still a continuation. Thus the nonstatutory double patenting rejection is made and maintained because the provisions of 35 U.S.C. 121 do not apply to continuation applications.
Applicant should request a corrected filing receipt to confirm correction of the change in relationship to the ‘549 patent so that it is recognized by the Office. See MPEP 211.02(a)(I) and 211.03.
Conclusion
9. All other objections and rejections recited in the Office Action of November 01, 2023 are withdrawn in view of Applicant’s amendments and arguments.
10. No claims allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached M-F 8:30-5:30 Eastern Time.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Janet L Epps-Smith can be reached at 571-272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PETER J REDDIG/Primary Examiner, Art Unit 1646