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, 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 October 09, 2025 has been entered.
2. Claims 1-17 are currently being examined.
Rejections Maintained
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.
3. Claims 1-9 and 11-16 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 9,815,901 B2 (Brogdon et al. Nov. 14, 2017, IDS).
The ‘901 claims are drawn to:
19. An isolated chimeric antigen receptor (CAR) polypeptide, wherein the CAR comprises a CD123 binding domain, a transmembrane domain, and an intracellular signaling domain, and wherein said CD123 binding domain comprises: (a) a heavy chain variable domain comprising three complementary determining regions of heavy chain complementary determining region 1 (HC CDR1), heavy chain complementary determining region 2 (HC CDR2), and heavy chain complementary determining region 3 (HC CDR3) present in order of HC CDR1, HC CDR2, and HC CDR3, wherein HC CDR1 comprises the amino acid sequence of SEQ ID NO: 487, HC CDR2 comprises the amino acid sequence of SEQ ID NO: 492, and HC CDR3 comprises the amino acid sequence of SEQ ID NO: 497; and a light chain variable domain comprising three complementary determining regions of light chain complementary determining region 1 (LC CDR1), light chain complementary determining region 2 (LC CDR2), and light chain complementary determining region 3 (LC CDR3) present in order of LC CDR1, LC CDR2, and LC CDR3, wherein LC CDR1 comprises the amino acid sequence of SEQ ID NO: 502, LC CDR2 comprises the amino acid sequence of SEQ ID NO: 507, and LC CDR3 comprises the amino acid sequence of SEQ ID NO: 512; or (b) a heavy chain variable domain comprising three complementary determining regions of heavy chain complementary determining region 1 (HC CDR1), heavy chain complementary determining region 2 (HC CDR2), and heavy chain complementary determining region 3 (HC CDR3) present in order of HC CDR1, HC CDR2, and HC CDR3, wherein HC CDR1 comprises the amino acid sequence of SEQ ID NO: 517, HC CDR2 comprises the amino acid sequence of SEQ ID NO: 522, and HC CDR3 comprises the amino acid sequence of SEQ ID NO: 527; and a light chain variable domain comprising three complementary determining regions of light chain complementary determining region 1 (LC CDR1), light chain complementary determining region 2 (LC CDR2), and light chain complementary determining region 3 (LC CDR3) present in order of LC CDR1, LC CDR2, and LC CDR3, wherein LC CDR1 comprises the amino acid sequence of SEQ ID NO: 532, LC CDR2comprises the amino acid sequence of SEQ ID NO: 537, and LC CDR3 comprises the amino acid sequence of SEQ ID NO: 542; or (c) a heavy chain variable domain comprising three complementary determining regions of heavy chain complementary determining region 1 (HC CDR1), heavy chain complementary determining region 2 (HC CDR2), and heavy chain complementary determining region 3 (HC CDR3) present in order of HC CDR1, HC CDR2, and HC CDR3, wherein HC CDR1 comprises the amino acid sequence of SEQ ID NO: 335, HC CDR2 comprises the amino acid sequence of SEQ ID NO: 363, and HC CDR3 comprises the amino acid sequence of SEQ ID NO: 391; and a light chain variable domain comprising three complementary determining regions of light chain complementary determining region 1 (LC CDR1), light chain complementary determining region 2 (LC CDR2), and light chain complementary determining region 3 (LC CDR3) present in order of LC CDR1, LC CDR2, and LC CDR3, wherein LC CDR1 comprises the amino acid sequence of SEQ ID NO: 419, LC CDR2 comprises the amino acid sequence of SEQ ID NO: 447, and LC CDR3 comprises the amino acid sequence of SEQ ID NO: 475.
20. The isolated CAR polypeptide of claim 19, comprising: (i) the amino acid sequence of the light chain variable region of SEQ ID NO: 276; or (ii) an amino acid sequence with 95-99% identity to the amino acid sequence of the light chain variable region of SEQ ID NO: 276.
21. The isolated CAR polypeptide of claim 19, comprising: (i) the amino acid sequence of the heavy chain variable region of SEQ ID NO: 217; or (ii) an amino acid sequence with 95-99% identity to the amino acid sequence of the heavy chain variable region of SEQ ID NO: 217.
22. The isolated CAR polypeptide of claim 19, comprising the amino acid sequence of the light chain variable region of SEQ ID NO: 276, and the amino acid sequence of the heavy chain variable region of SEQ ID NO: 217.
23. The isolated CAR polypeptide of claim 19, comprising: (i) the amino acid sequence of SEQ ID NO:480; (ii) an amino acid sequence having at least one, two or three modifications but not more than 10 modifications to SEQ ID NO: 480; or (iii) an amino acid sequence with 95-99% identity to SEQ ID NO: 4
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented CAR CD123 binding domain comprises the same HC CDRs, LC CDRs, light chain variable regions, and heavy chain variable regions as claimed. SEQ ID NO: 480 is a human scFv comprising a VH (SEQ ID NO: 217) domain and VL (SEQ ID NO: 276) domain joined by the linker SGGGGSGGGGSGGGGS, which comprises SEQ ID NO: 25. See Appendix and Example 1 of the instant specification.
Regarding claims 14 and 15, the claims do not specific an N-terminal or C-terminal orientation, thus the orientation of the light and heavy chains are not limited. Additionally, one of skill in the would have been motivated to optimize the light and heavy chain orientation to provide optimal binding activity.
4. Claims 10 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 9,815,901 B2 (Brogdon et al. Nov. 14, 2017, IDS) as applied to claims 1-9 and 11-16 above in view of US 2014/0322212 A1 (Brogdon et al. Oct. 30 2014, filed Feb. 20, 2014, IDS), “Brogdon”.
The ‘901 claims teach as set forth above, but do not teach a Fab domains comprising the CD123 binding domain or the linker of SEQ ID NO: 26.
Brogdon teaches making CD123 CARs. See abstract. Brogdon teaches that the binding domain of the CD123 CARs can comprise a Fab domain. See ¶¶ 0100 and 0193.
Brogdon teaches using linkers to join the variable domains of the CD123 binding domain, including SEQ ID NO: 126, GGGGSGGGGSGGGGSGGGGSGGGGSGGGGS, which comprises the currently claimed SEQ ID NO: 26. See ¶¶ 0010 and 0021.
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 the ‘901 claims and Brogdon and modify the binding domain of the ‘901 claims to a Fab domain and/or use the linkers of Brogdon in the binding domain because Brogdon teaches that the Fab domain and linkers can be used in the antigen binding domain of a CD123 CAR. One would have been motivated to modify the structure of the CD123 binding domain of the ‘901 claims to optimize its stability and/or binding activity.
Response to Arguments
5. Applicant argues that that filing a terminal disclaimer over the ‘901 reference patent would be premature at this stage in prosecution because other rejections are still outstanding, and thus, the final version of these claims is not yet known. At such time when allowable subject matter has been agreed on, Applicants will reconsider filing a terminal disclaimer over the ‘901 reference patent.
Applicant’s arguments have been considered, but have not been found persuasive. Claims 1-17 remain obvious over the ‘901 reference claims for the reasons of record and no terminal disclaimer has been filed. Thus, the rejections are maintained for the reasons of record.
6. Claims 1, 3-9 and 11-16 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6, 9, 11, 16, 33, 37, 43, 46, 50, 54, 64, 65, 69, 70, 73-75, 77, 87, 90, 93, 99, 104, 111, 112, and 167-182 of co-pending Application No. 16/093,758 (reference application published as US 2023/0071283 A1, IDS)
The ‘758 claims are drawn to:
6. A fusion protein comprising a degradation domain and a chimeric antigen receptor (CAR), wherein the degradation domain and the CAR are separated by a heterologous protease cleavage site, wherein the degradation domain has a first state associated with a first level of surface expression of the fusion protein and a second state associated with a second level of surface expression of the fusion protein, and wherein the second level is increased over the first level in the presence of a stabilization compound.
175. The fusion protein of claim 174, wherein said antigen binding domain binds an antigen selected from the group consisting of: CD19, CD123, BCMA, and CD20.
176. The fusion protein of claim 174, wherein:
(i) said antigen binding domain comprises an amino acid sequence selected from any one of SEQ ID NOs: 356-368 or 381;
(ii) said antigen binding domain comprises an amino acid sequence selected from any one of SEQ ID NOs: 751, 756, 761, or 766;
(iii) said antigen binding domain comprises an amino acid sequence selected from any one of SEQ ID NOs: 382, 386, 390, 394, 398, 402, 406, 410, 414, 418, 422, 426, 430, 434, 438, 442,
(iv) said antigen binding domain comprises an amino acid sequence comprising amino acid residues 470-712 or 470-939 of SEQ ID NO: 3033.
Although the claims at issue are not identical, they are not patentably distinct from each other because the patented the CAR CD123 binding domain comprises the same HC CDRs, LC CDRs, light chain variable regions, and heavy chain variable regions as claimed. SEQ ID NO: 751 comprises the instantly claimed SEQ ID NO: 480. SEQ ID NO: 480 is a human scFv comprising a VH (SEQ ID NO: 217) domain and VL (SEQ ID NO: 276) domain joined by the linker SGGGGSGGGGSGGGGS, which comprises SEQ ID NO: 25. See Appendix and Example 1 of the instant specification.
Regarding claims 14 and 15, the claims do not specific an N-terminal or C-terminal orientation, thus the orientation of the light and heavy chains are not limited. Additionally, one of skill in the would have been motivated to optimize the light and heavy chain orientation to provide optimal binding activity.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
7. Claims 10 and 17 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 6, 9, 11, 16, 33, 37, 43, 46, 50, 54, 64, 65, 69, 70, 73-75, 77, 87, 90, 93, 99, 104, 111, 112, and 167-182 of co-pending Application No. 16/093,758 (reference application published as US 2023/0071283 A1, IDS) as applied to claims 1, 3-9 and 11-16 above in view of US 2014/0322212 A1 (Brogdon et al. Oct. 30 2014, filed Feb. 20, 2014, IDS), “Brogdon”.
The ‘758 claims teach as set forth above, but do not teach a Fab domains comprising the CD123 binding domain or the linker of SEQ ID NO: 26.
Brogdon teaches as set forth above.
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 the ‘758 claims and Brogdon and modify the binding domain of the ‘758 claims to a Fab domain and/or use the linkers of Brogdon in the binding domain because Brogdon teaches that the Fab domain and linkers can be used in the antigen binding domain of a CD123 CAR. One would have been motivated to modify the structure of the CD123 binding domain of the ‘758 claims to optimize its stability and/or binding activity.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
8. Applicant argues that according to M.P.E.P. § 804(1)(B)(1)(b)@), when “a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having an earlier patent term filing date [compared to the reference application(s)], the examiner should withdraw the rejection in the application having the earlier patent term filing date and permit that application to issue as a patent...”
Applicant argues that the present application has an earliest patent term filing date of August 19, 2015. Therefore, the present application has an earlier effective U.S. filing date as compared to the ‘943 reference application (which has an earliest patent term filing date of July 14, 2017) and the ‘758 application (which has an earliest patent term filing date of April 14, 2016). Therefore, the present provisional nonstatutory double patenting rejections should be withdrawn.
Applicants’ arguments have been considered, but have not been found persuasive. With regard to the ‘758 claims, this is not the only remaining rejection and the claims of the instant application are still obvious in view of the co-pending claims and a terminal disclaimer has not been filed. MPEP 804 I-B states: “The “provisional” double patenting rejection should continue to be made by the examiner in each application as long as there are conflicting claims in more than one application unless that “provisional” double patenting rejection is the only rejection remaining in at least one of the applications.” Thus, the rejection is maintained with regard to the ‘758 claims.
It is noted that with regard to the ‘943 claims, the rejection is withdrawn in view of Applicant’s arguments with respect to the ‘819 and ‘583 patents given that the ‘943 claims are method claims like that of the ‘819 and ‘583 patents.
Conclusion
9. All other objections and rejections recited in the Office Action of April 10, 2025 are withdrawn in view of Applicant’s arguments of October 09, 2025.
10. No claims allowed.
11. All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
12. 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 on 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 on 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 1642
Prosecution Insights