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. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 04/24/2026 has been entered.
Claims 36, 38, 40-46, 48 and 51-68 are pending.
Claims 64-66 stand withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected Inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 02/28/2025.
Claims 36, 38, 40-46, 48, 51-63 and 67-68 are presently under consideration.
3. 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.
4. Claims 36, 38, 40-46, 48, 51-63 and 67-68 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
(i) Claim 36 is indefinite, because the recitation of “the construct” lacks proper antecedent basis in preceding parts of the claim.
(ii) Claim 68 is indefinite as being in improper Markush format. The Office recommends the use of the phrase "selected from the group consisting of ..." with the use of the conjunction "and" rather than "or" in listing the species. See MPEP 803.02.
(iii) Claims 38, 40-46, 48, 51-63 and 67-68 are indefinite, because they encompass the indefinite limitations of the claim(s) on which they depend.
In view of the above, a person of ordinary skill in the art cannot unequivocally interpret the metes and bounds of the claims so as to understand how to avoid infringement. Applicant is reminded that any amendment must point to a basis in the specification so as not to add New Matter. See MPEP 714.02 and 2163.06.
5. The following is a quotation 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.
6. Claims 36, 38, 40-46, 48, 51-63 and 67-68 are rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement. The claim(s) contain(s) 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, at the time the application was filed, had possession of the claimed invention. This is a New Matter rejection.
Applicant does not point out the support for the amendment, and the disclosure as-filed does not appear to provide adequate written description of the following newly added limitations:
(i) Neither the specification nor the claims as originally filed provide adequate written description of an extracellular segment which “consists of amino acids 99-134 of SEQ ID NO: 10.”
(ii) Neither the specification nor the claims as originally filed provide adequate written description of newly added limitation “wherein the construct does not comprise a third intracellular segment comprising an intracellular signaling domain of a third receptor protein.” The specification discloses in Example 2 one specific CoStAR comprising only CD28 and CD40 costimulatory domain, which is insufficient to support the full scope of a genus of all possible pairwise combinations, in either order, of the 23 members recited in claim 36(b).
The amended claims now recite limitations which were not clearly disclosed in the specification or claims as filed, and change the scope of the instant disclosure as filed. These limitations introduce new concepts and violate the description requirement of 35 U.S.C. 112(a).
Applicant is required to cancel the New Matter in the response to this Office Action. Alternatively, Applicant is invited to clearly point out the written support for the newly added limitations.
7. 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
8. Claims 36, 38, 42-44, 51-52, 57-58 and 61-63 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Wang et al. (US 20180201902).
Wang teaches chimeric costimulatory receptors (CCRs) which comprise a single domain antibody, an extracellular hinge region and a transmembrane domain from CD8 or CD28, and intracellular signaling domains of CD28 and 4-1BB but do not comprise a third intracellular segment comprising an intracellular signaling domain of a third receptor protein (e.g. [0056], [0090], [0105]), which are within the scope of instant claims 36(b), 38, 42-44, 51-52, 57-58 and 61-63, thereby anticipating these claims.
9. 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 of this title, 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.
8. Claims 36, 38, 40, 42-45, 48, 51-63 and 67-68 are rejected under 35 U.S.C. 103 as being unpatentable over Lock et al. (US 20190388468) in view of Gottschalk et al. (US 20210252058).
Embodiment (b) of claim 36 is directed to a chimeric costimulatory receptor comprising:
(i) a disease- or tumour-associated antigen binding domain, linked to
(ii) an extracellular segment of a stimulatory receptor protein, linked to
(iii) a transmembrane domain, linked to
(iv) a first intracellular segment comprising an intracellular signaling domain of a receptor protein, and linked to
(v) a second intracellular segment comprising an intracellular signaling domain of a second receptor protein,
wherein the extracellular segment, first intracellular segment, and second intracellular segment are independently segments from: CD2, CD9, CD26, CD27, CD28, CD29, CD38, CD43, CD46, CD49d, CD55, CD73, CD81, CD82, CD99, CD100, CD134 (OX40), CD137 (41BB), CD150 (SLAM), CD270 (HVEM), CD278 (ICOS), CD357 (GITR), and EphB6, and
wherein the construct does not comprise a third intracellular segment comprising an intracellular signaling domain of a third receptor protein.
Lock teaches chimeric costimulatory receptors (CCR) which comprise an antigen-binding domain, a transmembrane domain, and cytoplasmic costimulatory domains, but do not comprise or does not consist of an ITAM containing domain such as CD3ζ or another primary cytoplasmic signaling domain (e.g. [0031], [0079], [0105]).
Lock describes a working example of an anti-CD20 CCR comprising intracellular costimulatory signaling domains of CD28 and 4-1BB, which does not comprise a third intracellular segment comprising an intracellular signaling domain of a third receptor protein (e.g. [0012]-[0017]). CCR costimulatory domains can also be from CD2, CD27, CD40, CD46, OX40, HVEM or ICOS, among others (e.g. [0030], [0031], [0079], [0105], [0185], [0195]).
CCRs also comprise a linker or a spacer or a hinge between the antigen binding domain and the transmembrane domain (e.g. [0012], [0179], [0248]), which is within the scope of the “extracellular segment” recited in instant claims. Lock exemplifies transmembrane domains derived from CD8 and CD28, and spacer/hinge region derived from CD8 (e.g. [0012], [0179], [0248]).
While Lock does not specifically exemplify the extracellular segment derived from one of the molecules listed in instant claim 36(b), Gottschalk teaches CCRs comprising both the transmembrane domain and the extracellular hinge region segment from either CD8 or CD28 (e.g. [0095], [0102], claims 9 and 23).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to test various extracellular segments, including one from CD28, in Lock’s CCRs, to optimize receptor function for each antigen-binding domain, because the optimal nature and length of extracellular spacer or linker domain connecting the antigen-binding domain to the transmembrane domain depends on the nature of the antigen and on the specific properties of the antigen-binding domain, as one of skill in the art would be aware. For example, Gottschalk teaches adjusting the size of the linker domain to ensure that the antigen-binding moiety is an optimal distance from the transmembrane domain (e.g. [0095]).
More specifically, Gottschalk teaches chimeric antigen receptor (CAR) molecules comprising an antigen-binding domain, a linker domain, a transmembrane domain, a cytoplasmic lymphocyte activation domain and a and a CD40 cytoplasmic signaling domain (e.g. claims 1 and 22), wherein the lymphocyte activation domain is one of DAP10, DAP12, FCER1G, CD3ζ, CD3ε, CD3γ, CD3ζ, CD5, CD22, CD226, CD79A and CD79B (e.g. claim 18, and [0111]). As such, Gottschalk’s CAR does not comprise a third intracellular segment comprising an intracellular signaling domain of a third receptor protein.
Gottschalk further exemplifies CAR extracellular linker domain as “all or part of the extracellular region of CD8, CD4 or CD28” [0095], i.e. Gottschalk specifically teaches the complete extracellular region of CD28. The transmembrane domain is derived from CD8, CD8α, CD4, CD3ζ, CD28, CD40, CD134 (OX-40), or CD7 (e.g. claim 9).
Additionally, Gottschalk teaches co-stimulatory fusion proteins ([0129]-[0135]). “In certain embodiments, the co-stimulatory fusion protein comprises an extracellular target-binding domain (as disclosed above), a transmembrane domain (as described above) and a cytoplasmic domain, wherein the cytoplasmic domain comprises at least one co-stimulatory protein (as described above). In certain embodiments, the co-stimulatory fusion protein does not comprise a lymphocyte activation domain (e.g., Cd3ζ).” [0132] Non-limiting examples of co-stimulatory proteins include 4-1BB (CD137), CD28, ICOS, CD134 (OX-40), BTLA, CD27, CD30, GITR, CD226, and HVEM [0119].
The combined teachings of Lock and Gottschalk would have provided both the motivation and the expectation of success to those of ordinary skill in the art before the effective filing date of the claimed invention to combine the elements of chimeric receptors as recited in instant claims 36, 38, 42-45, 48, 51-52, 57-58, 61, 63 and 67-68 in order to optimize the receptor properties for each particular antigen-binding domain.
Claim 53 is included in the rejection, because Gottschalk teaches folate receptor as a target [0082]. Claims 54-55 are included, because Gottschalk teaches receptors fused to epitope tags [0013]. Claims 53, 59-60 and 62 are included, because Gottschalk teaches co-stimulatory fusion proteins introduced into the host cell on the same vector as the CAR but separated by a separation sequence such as 2A [0135].
In view of the above, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, as evidenced by the references, especially in the absence of evidence to the contrary.
9. 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 §§ 706.02(l)(1) - 706.02(l)(3) 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.
10. Claims 36, 38, 40-46, 48, 51-63 and 67-68 stand rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of U.S. Patents No. 12187778 and 11945876 (both of record).
Claims 36, 38, 40-46, 48, 51-63 and 67-68 stand provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of copending applications USSN 17/843480, 17/936102, 18/005330, 18/157027, 18/316548, and 18/719985 (all of record).
Applicant has not substantively addressed the grounds of rejection presented in sections 10-12 of the Office action dated 03/18/2025, which are therefore maintained and incorporated by reference herein as if reiterated in full.
11. The following prior art is cited of record but not presently relied upon:
US 20220074945, e.g. claims 16-18, [0172], [0269];
US 20200207852, e.g. [0097];
US 20200399355, e.g. [0214];
US 20200308234, e.g. [0444];
US 20190055312, e.g. [0185];
US 20190023761, e.g. [0411];
US 20180305433, e.g. [0107];
US 20200317777; e.g. [0195].
12. Conclusion: no claim is allowed.
13. Any inquiry concerning this communication or earlier communications from the examiner should be directed to ILIA I OUSPENSKI whose telephone number is (571)272-2920. The examiner can normally be reached 9 AM - 5:30 PM.
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, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ILIA I OUSPENSKI/ Primary Examiner, Art Unit 1644
Prosecution Insights