DETAILED ACTION
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Applicant’s amendment filed on May 21, 2026 is acknowledged.
Claims 1, 2, 5, 6, 8-11, 14-16, 20-27, 30-34, 36, have been canceled.
Claims 45 and 46 have been added.
Claims 3, 4, 7, 12, 13, 17-19, 28, 29, 35, and 37-46 are pending.
Claims 29, 39, and 43 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 29, 2025.
Claims 3, 4, 7, 12, 13, 17-19, 28, 35, 37, 38, 40-42, and 44-46 are currently under consideration as they read on the elected species.
The elected species are:
i) CD30 as the targeted antigen and SEQ ID NOs: 14 and 15 for the antigen binding domain.
ii) SEQ ID NO:26 as the signaling domain,
iii) CD28 as the molecule and SEQ ID NO:20 as the transmembrane domain,
iv) SEQ ID NO: 35 as the amino acid sequence for the CAR.
3. In view of applicant’s amendment, following rejections are set forth.
4. 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.
5. Claims 3, 4, 7, 12, 13, 17-19, 28, 35, 37, 38, 40-42, and 44-46 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claims contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention for the reasons of record.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant argues that the reference Edwards et al. cited by the Examiner support that the instant claims are enabled in that Edwards teaches a single protein can be used to generated over 1,000 different antibodies which demonstrate well established methods in the art to generation antibodies to CD30 antigen.
Applicant further states:
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Applicant asserts that CAR-T cell therapy was well-developed in the art and method of constructing CAR-T cells and administering the cells to patients were routine as evidenced by Chmielewski (disclosing CD30 CAR with 98.1% sequence identity to the instant SEQ ID NO:35), Rooney and Savoldo (both teach detailed method for generating virus specific CAR-T or CD30 CAR EBC-CTLs. Applicant asserts that the Examiner cannot simultaneously assert that the claimed is obvious and not enabled.
Furthermore, applicant asserts that the prevention claims are also enabled in that treating or preventing an alloreactive immune response such as GVHD or graft rejection encompasses readily identifiable patient population. Applicant also argues that no screening protocols is required because the at-risk population is defied by the medical procedure itself. Applicant asserts that claims 19, 28, 37, 38, 41, and 42 have been amended to recite the specific CDR sequences for the antigen binding domain, and these amendments further defined the structural features of the anti-CD30 binding domain and addressed any remaining concerns about the claims.
As such, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
In contrast to applicant’s assertion based on the teachings of Edwards et al., note the instant claims (e.g. claim 3, 4, 7, 12, 13, 17, and 18) are broadly drawn to a method of treating or preventing a disease or condition characterized by an alloreactive immune response by administering a virus-specific immune cell comprising a CAR comprising any antigen-binding domain that binds CD30. The genus of the antigen-binding domain that binds CD30 is a broad genus because it encompasses various specificities and epitopes unrestricted in antigen-binding region structure, epitopes to which they bind, function, mechanism of action in treatment.
Contrary to applicant’s reliance on the working examples, note that the working examples in the instant specification discloses two anti-CD30 antibodies, HRS3 and FMC63 and administer the CD30 CAR EBVSTs (peripheral blood mononuclear cells) as allogeneic adoptive cell therapy for CD30+ lymphoma patients (e.g. see Examples 1 and 5 in the instant specification as-filed).
While the instant specification disclosed CD30 antigen including human CD30 isoforms 1-3 and various structures of CD30 including signal peptide, extracellular domain, transmembrane domain, and cytoplasmic domain (e.g. see Sequences listed in pages 77-78 of the specification as-filed), an unreasonable amount of experimentation would be needed to make and use the invention based on the disclosure. Based on the disclosure, one would not know whether any anti-CD30 antibody would be able to be added to the CAR for a method of treating or preventing a disease or condition characterized by alloreactive immune response. One would not know if the binding affinity or epitope of the anti-CD30 antibody would impact the ability to treat. The only guidance provided is to create a wide range of anti-CD30 antibodies and screen each one to determine the impact in virus-specific immune cells and the ability to treat disease. This amounts to little more than impermissible “trial and error” or a “hunting license.” See Baxalta, 81 F.4th 1362 at 1367; Amgen, 143 S. Ct. at 1257.
Therefore, the Specification does not enable one of ordinary skill in the art to make or use the claimed invention without undue or unreasonable experimentation.
Further, applicant argues that it is inappropriate to simultaneously set forth rejections under 35 USC 112 1st paragraph enablement and 35 USC103(a).
This argument is not persuasive because there is no statutory bar that if a rejection is made under one statute, another rejection cannot be made under a different statute. The courts have ruled that enablement and art are distinct issues, stating in Rasmusson v. SmithKlein Beecham Corp., 75 USPQ2d 1297 (CAFC 2005), that:
“The standard for what constitutes proper enablement of a prior art reference for purposes of anticipation under section 102, however, differs from the enablement standard under section 112. In In re Hafner, 410 F.2d 1403 161 USPQ 783 (CCPA 1969), the court stated that “a disclosure lacking a teaching of how to use a fully disclosed compound for a specific, substantial utility or of how to use for such purpose a compound produced by a fully disclosed process is, under the present state of the law, entirely adequate to anticipate a claim to either the product or the process and, at the same time, entirely inadequate to support the allowance of such a claim.” Id. at 1405; see Schoenwald, 964 F.2d at 1124; In re Samour, 571 F.2d 559, 563-64 197 USPQ 1 (CCPA 1978). The reason is that section 112 “provides that the specification must enable one skilled in the art to 'use' the invention whereas [section] 102 makes no such requirement as to an anticipatory disclosure.” Hafner, 410 F.2d at 1405; see 1 Donald S. Chisum, Chisum on Patents §3.04[1][c] (2002); see also In re Cruciferous Sprout Litig., 301 F.3d 1343, 1349-52 64 USPQ2d 1202 (Fed. Cir. 2001) (finding anticipation where applicant sought a patent based on a new use for a previously disclosed method).”
In the instant case, the specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims. However, a skilled artisan would have been motivated to perform the recited methods steps at the time the instant application was filed because the structurally defined anti-CD30 CAR T cell that is also EBC specific can be redirected to eliminate CD30+ tumor cells and thus rejections were also set forth under 35 USC 103(a).
Furthermore, in contrast to applicant’s arguments that prevention claims are enabled, the problem here is the scope of the claims encompass preventing a disease or condition characterized by alloreactive immune response by administering a prophylactically effective amount of the CAR comprising an antigen-binding domain to CD30. There is insufficient evidence in the instant specification to show that administering the CD30 CAR in a virus-specific immune cells can be administered to prevent un specified alloreactive immune response.
Moreover, regarding claims 19, 28, 37, 38, 41, and 42, they recite only some partial structures of the CD30 CAR, e.g. only the signaling domain amino acid sequence at least 80% identical to of SEQ ID NO:26, in view of the recitation of “and/or”.
In addition, regarding preventing by administering prophylactically effective quantity of the virus-specific immune cells comprising the CD30 CAR, note that the instant specification discloses administering CD30 CAR EBVSTsfor CD30+ lymphoma and states that none of the patients experienced dose-limiting toxicities and no cytokine release syndrome or GVHD. However, the scope of the claims does not set forth any specific disease.
The specification does not provide guidance as to how one skilled in the art would go about screening those patients having a disease or condition characterized by an alloreactive immune response. Nor is guidance provided as to a specific protocol to be utilized in order to prove the efficacy of the presently claimed virus-specific immune cells in preventing these diseases. Additionally, the specification fails to enable “treating” to the extent such treatment includes the prevention of a disease state. Accordingly, undue experimentation is necessary to determine screening and testing protocols to demonstrate the efficacy of the presently claimed invention.
Therefore, applicant’s arguments have not been found persuasive.
6. Claims 3, 4, 7, 12, 13, 17-19, 35, 37, 40, 41, and 44-46 are 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 for the reasons of record.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant argues that the instant specification provides extensive guidance on various embodiments of the CD30 CAR including the exemplified SEQ ID NOs: 14 and 15 for antigen binding as well as sequences for transmembrane domain and signally domain and the specifically fully demonstrates possession of the claimed method. Applicant asserts that the instant claims are drawn to a method not product. Applicant asserts that the specification discloses the method therefore applicant is in possession of the methods. As such, applicant asserts the rejection should be withdrawn.
This is not found persuasive for following reasons:
Contrary to applicant’s arguments, note that the issues remain to be that none of the instant independent claims 3, 12, and 18 recite any structure for the administered product CD30 CAR that provides for the function of CD30 binding and being able to treat or prevent a disease or condition. As to the amended dependent claims 19, 37, and 4, they recite “and/or” with respect to the sequences of the signaling domain, transmembrane domain, and the antigen-binding domain which render the claims to recite only partial structure, e.g. only signaling domain comprises at least 80% sequence identity to SEQ ID NO:26 but not the antigen binding domain in view of the use of “and/or”. Thus, all present claims utilize only functional language to describe the product which is necessarily administered in the instant claims. the specification does disclose working examples which utilized a CD30 CAR with specific amino acid sequences for each component. However, this CD30 CAR species is not reasonably representative of the species of all possible CD30 CAR because of the structural diversity found in antibodies that bind the same antigen as discussed above. Further, as has been discussed above, identifying an antibody simply on the basis of what it binds rather than by identifying the sequence/structure of the antibody in question is generally insufficient to provide sufficient written description of the antibody in question. Logically, if applicant was not in possession of the CAR which is being administered, applicant also was not in possession of methods of administering or contacting such reagents at the time the instant application was filed.
As such, applicant’s arguments have not been found persuasive.
7. 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.
8. 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.
9. Claims 3, 4, 7, 12, 13, 17-19, 28, 35, 37, 38, 40-42, and 44-46 are rejected are rejected under 35 U.S.C. 103 as being unpatentable over Chmielews et al. (US 2016/0200824, reference on IDS) in view of Rooney et al. (WO 2018/052947) and Savoldo et al. (Blood 2007, 110(7):2620-2630) for the reasons of record.
As shown in the previous Office Action mailed on February 25, 2026, Chmielewski et al. teach a CD30 CAR of SEQ ID NO:3 contains all component of the instant CD30 CAR including antigen-binding region comprising SEQ ID NO:14 and 15, a transmembrane domain, a signaling domain comprising the amino acid sequence that is 90.3% identical to instant SEQ ID NO:26, an ITAM.
Further, the prior art SEQ ID NO:3 also contain amino acid sequences that are identical to the instant HC-CDR1, HC-CDR2, and HC-CDR3 sequences and LC-CDR1, LC-CDR2, and LC-CDR3:
Instant SEQ ID NOs: 8-9-10 fused alignment:
RESULT 47
US-14-912-937-3
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 3, US/14912937
Publication No. US20160200824A1
GENERAL INFORMATION
APPLICANT: Universitaet zu Koeln
TITLE OF INVENTION: Anti CD30 chimeric antigen receptor and its use
FILE REFERENCE: 4677-003
CURRENT APPLICATION NUMBER: US/14/912,937
CURRENT FILING DATE: 2016-02-19
PRIOR APPLICATION NUMBER: EP13181668.8
PRIOR FILING DATE: 2013-08-26
NUMBER OF SEQ ID NOS: 10
SEQ ID NO 3
LENGTH: 690
TYPE: PRT
ORGANISM: artificial sequence
FEATURE:
OTHER INFORMATION: fusion polypeptide
Query Match 86.2%; Score 159.5; Length 690;
Best Local Similarity 36.8%;
Matches 32; Conservative 0; Mismatches 0; Indels 55; Gaps 2;
Qy 1 GYTFTTYT-----------------INPSSGCS--------------------------- 16
|||||||| ||||||||
Db 49 GYTFTTYTIHWVRRRPGHDLEWIGYINPSSGCSDYNQNFKGKTTLTADKSSNTAYMQLNS 108
Qy 17 -----------ARRADYGNYEYTWFAY 32
||||||||||||||||
Db 109 LTSEDSAVYYCARRADYGNYEYTWFAY 135
Instant SEQ ID NOs: 11-12-13 fused alignment to prior art SEQ ID NO:3:
RESULT 13
US-14-912-937-3
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 3, US/14912937
Patent No. 10808035
GENERAL INFORMATION
APPLICANT: Universitaet zu Koeln
TITLE OF INVENTION: Anti CD30 chimeric antigen receptor and its use
FILE REFERENCE: 4677-003
CURRENT APPLICATION NUMBER: US/14/912,937
CURRENT FILING DATE: 2016-02-19
PRIOR APPLICATION NUMBER: EP13181668.8
PRIOR FILING DATE: 2013-08-26
NUMBER OF SEQ ID NOS: 10
SEQ ID NO 3
LENGTH: 690
TYPE: PRT
ORGANISM: artificial sequence
FEATURE:
OTHER INFORMATION: fusion polypeptide
Query Match 73.9%; Score 71.7; Length 690;
Best Local Similarity 25.4%;
Matches 18; Conservative 0; Mismatches 0; Indels 53; Gaps 2;
Qy 1 QNVGTN-----------------SAS---------------------------------- 9
|||||| |||
Db 188 QNVGTNVAWFQQKPGQSPKVLIYSASYRYSGVPDRFTGSGSGTDFTLTISNVQSEDLAEY 247
Qy 10 --QQYHTYPLT 18
|||||||||
Db 248 FCQQYHTYPLT 258
Therefore, Chmielewski et al. teaches the instant CDR30 CAR.
Applicant’s arguments have been fully considered but have not been found persuasive.
Applicant asserts that none of the references teaches using CD30 CAR T cells to address alloreactivity or administering such cells in a transplant context to treat or prevent graft-versus-host or graft rejection.
Applicant states:
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Applicant asserts that applicant’s data demonstrate that CD30 CAR EBVSTs selectively target alloreactive T cells while sparing beneficial immune cells and avoiding self-destruction which is unexpected results and would not have been predictable to in view of the prior art.
Applicant asserts that even if one of skill in the art could have been combined, it would only be used to treat cancer, not for treating or preventing alloreactive immune response.
As such, applicant asserts that the rejection should be withdrawn.
This is not found persuasive for following reasons:
In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., a transplant context to treat or prevent graft-versus-host or graft rejection) are not recited in the rejected claims. Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Further, applicant’s arguments rely on language solely recited in preamble recitations in the claims. However, when reading the preamble in the context of the entire claim, the recitation treating or preventing a disease or condition characterized by an alloreactive immune response or allotransplantation or killing alloreactive immune cells is not limiting because the body of the claim describes single step of administering the CD30 CAR in virus-specific immune cells and the language recited solely in the preamble does not provide any distinct definition of any of the claimed invention’s limitations. Thus, the preamble of the claims is not considered a limitation. See Pitney Bowes, Inc. v. Hewlett-Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165 (Fed. Cir. 1999). See MPEP § 2111.02.
Here, given that the recited CD30 CAR T cells were readily available as disclosed by Chmielewski et. al, and given that both Rooney and Savoldo teach the benefits of using EBV allogeneic T cells for making CAR T cells including CD30 CAR T cells in in vivo expansion and persistence and provide detailed methods of making allogeneic EBV CAR T cells, an ordinary skill in the art would have been motivated to produce virus-specific CD30 CAR T cells to administer the CD30 CAT T cells to treat CD30+ lymphomas with a reasonable expectation of success. The administering of the CD30 EBV CAR T cells would inherently/intrinsically treat or prevent the alloreactive immune response induced by the allogenic CAR T cells.
As such, applicant’s arguments have not been found persuasive.
10. 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.
11. Claims 3, 4, 7, 12, 13, 17-19, 28, 35, 37, 38, 40-42, and 44-46 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 5, 7, 9, 11, 14, and 18 of copending USSN 17/997,154 (reference application) in view of Savoldo et al. (Blood 2007, 110(7):2620-2630) for the reasons of record.
Applicant requests to the provisional nonstatutory double patenting rejection be held in abeyance. As such, the rejection is maintained for the reasons of record.
12. No claim is allowed.
13. THIS ACTION IS MADE FINAL. 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.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHUN DAHLE whose telephone number is (571)272-8142. The examiner can normally be reached Mon-Fri 6:30am-4:00pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Misook Yu can be reached at 571-272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHUN W DAHLE/Primary Examiner, Art Unit 1641
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