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 .
Applicant’s amendment, filed on 12/19/2025, is acknowledged.
Claims 13-26 are cancelled.
Claims 1-12 are currently pending.
Election/Restrictions
Applicants’ election without traverse of Group I, claims 1-12, directed to an antigen binding receptor, filed on 12/18/2025, is acknowledged.
Priority
Applicant’s claim for the benefit of a prior-filed European Patent Application No. 20189196.7, filed August 3, 2020 and European Patent Application No. 21158659.9, filed February 23, 2021, is acknowledged.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 6/14/2023, 1/22/2025, 5/16/2025, and 8/21/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner in their entireties.
Specification
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
The abstract is objected to because it uses phrases which can be implied, such as: “[t]he present invention generally relates to…”
The use of the terms “Labchip” (pg. 113), “TSKGel” (pg. 113), “Lenti-X” (pg. 113), “GloResponse” (pg. 114 and 118), “GlutaMAX” (pg. 114), are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore, the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112
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.
Claims 1-12 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 claims contain 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 inventors, at the time the application was filed, had possession of the claimed invention.
Instant claim 1 recites an antigen binding moiety with VH and VL CDR amino acid sequences but no recitation of the epitope in which the binding moiety specifically binds.
These claims, given its broadest reasonable interpretation consistent with the instant specification, reads on the genus of CARs comprising an antigen binding moiety comprising a VH CDR1-3 and VL-CDR1-3 regions of SEQ ID NOs: 1, 2/40, 3 and 4, 5, 6, respectively, in the context of any non- specified framework and further paired with any non-specified VL/VH. The claims fail to cite that the antibody is capable of forming an Fc mutant (P329G) antigen binding site. The claims do not specify the antigen to which the claimed antibody binds. While the CDR are important for binding and contribute the majority of contact residues with the target antigen, the antigen specificity, i.e., Fc mutant (P329G) is essential for identifying the other VL/VH missing framework. Accordingly, the skilled in the art would not be able to screen for any binding in the absence of antigen specificity to screen for the missing VL/VH framework in the claims.
The current state of the art in epitope structure prediction is limited given the noncontiguous amino acid residues constitute most epitopes, and that the dynamics of binding is often not integrated into the epitope prediction equation, making epitope structure prediction a complex four-dimensional problem (see Van Regenmortel, page 464, abstract in particular; Methods: A Companion to Methods of Enzymology 9:465-472, 1996). Van Regenmortel notes that 90% of antibodies raised against intact proteins do not react with any peptide fragment derived from the parent protein indicating that these antibodies are directed to discontinuous epitopes (see page 466, column 1 in particular). In addition, Van Regenmortel states that the low success rate of antigenic prediction is due to the fact that predictions concern only continuous epitopes and it is unrealistic to reduce the complexity of epitopes that always possess conformational features to one-dimensional, liner peptide models (see page 467, column 2 in particular). Detailed information regarding the specific epitopes recognized by the anti-α2 antibodies. A skilled artisan would require guidance, such as information regarding the specific epitope recognition of the antibodies successfully used in the instant invention in order to antibodies other than the specific clones in a manner reasonably commensurate with the scope of the claims. Claims 2-12 do not resolve this issue and are also rejected under 112(a) WD.
Amending claim 1 to recite the epitope in which the antigen binding moiety binds to (in the instant case, the antibody specifically binds to a mutated Fc domain comprising the P329G mutation according to EU numbering) will resolve this issue.
Further, the claims use open language "comprising" and "a heavy/light chain variable domain (VH/VL) comprising . . . a heavy chain complementary determining region (CDR)1 of SEQ ID NO: X, a HCDR 2 of SEQ ID NO:Y . . . ", the phrase results in an antigen binding moiety comprising the claimed CDRs or any portion of the claimed "SEQ ID NO: X". The claim terminology "a CDR 2 of SEQ ID NO: X" does not place size limits on the VH/VL/CDRs, but rather reads on any portion of the claimed VH/ VL/ CDRs of SEQ ID NO. The VH/VL/CDRs are generic with respect to size, encompassing anything from dimers on up to the full size of the claimed SEQ ID NOs. Replacing the article “a” with the definite article “the” would overcome this part of the rejection.
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.
Claims 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 9, 10 12-15, 17, 21, 22, 24, 25, 27, 28, 32, 33, 38, 41, 46-48, 53-55, 57, 62, 63, 70-74, 76, 84-86, and 90 of copending Application No. 18/067,330 (herein App ‘330) in view of Stubenrauch et al. (U.S. PGPub 20200093860).
App ‘330 claims antigen receptors comprising antigen binding moieties comprising a VH of SEQ ID NO: 19 (claim 22), which is 100% identical to instant SEQ ID NO: 8 (i.e., the limitations of instant claim 2):
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFSRYWMNWVRQAPGKGLEWVGEITPDSSTINY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFSRYWMNWVRQAPGKGLEWVGEITPDSSTINY 60
Qy 61 APSLKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARPYDYGAWFASWGQGTLVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 APSLKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARPYDYGAWFASWGQGTLVTVSS 119
And a VL of SEQ ID NO: 13 (claim 22), which is 100% identical to instant SEQ ID NO: 9 (i.e., the limitations of instant claim 3):
Qy 1 QAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTNKRAPGT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTNKRAPGT 60
Qy 61 PARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNHWVFGGGTKLTVL 109
|||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNHWVFGGGTKLTVL 109
App ‘330 does not claim antigen binding complexes moieties further comprising the components of instant claims 4-12.
Stubenrauch et al., in the same field of endeavor, teaches anti-P329G antigen receptors comprising an anti-P329G antigen binding moiety, a CD28 TM domain (i.e., the limitations of instant claims 1 and 4), a CD28 co-stimulatory domain (i.e., the limitations of instant claims 5, 7, and 8), and a CD3ζ stimulatory signaling domain (i.e., the limitations of instant claims 5, 6, and 9; Stubenrauch et al. Fig. 1):
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901
1055
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Stubenrauch et al. further teaches that these antigen receptors can be used in methods of treatment, including treating cancer with T-cells comprising an antigen binding receptor comprising an anti-P329G antigen binding moiety (Fig. 4 and ¶[0095]). Specifically, Stubenrauch et al. teaches that an anti-tumor antigen antibody with the P329G mutation can be administered with T-cells comprising the anti-P329G antigen receptor, leading to targeting of the T-cells to the tumor cells (Fig. 4 and 5):
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670
559
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It would have been obvious to one of ordinary skill in the art, before the effective filing date of the instant application, to have modified App ‘330 in view of Stubenrauch et al. to generate antigen receptors comprising the anti-P329G antigen binding moiety of App ‘330, as Stubenrauch et al. teaches that anti-P329G antigen binding moieties can be incorporated into antigen receptors. One would have been motivated to make this change for the purposes of generating anti-P329G antigen receptors to be used in the treatment of cancer.
Regarding instant claim 10, Stubenrauch et al. further teaches that the co-stimulatory domain can be the intracellular domain of CD137 (claim 6), and the stimulatory signaling domain can be the intracellular domain of CD3ζ (claim 5), meeting the limitations of this claim.
Regarding instant claim 11, Stubenrauch et al. teaches that the anti-P329G antigen binding moiety is connected to the TM domain via a linker (see Fig. 1 supra).
Regarding instant claim 12, Stubenrauch et al. teaches that the VH and VL are connected via a peptide linker, meeting the limitations of the claim (Fig. 1A and ¶[0202]): “…consisting of an heavy chain variable domain (VH), an light chain variable domain (VL) and a linker, wherein said variable domains and said linker have one of the following configurations in N-terminal to C-terminal direction: a) VH-linker-VL orb) VL-linker-VH. In a preferred embodiment, the scFv fragment has the configuration VH-linkerVL.”
The invention encompassed by the instant claims was a prima facie obvious variant of the invention claimed by App ‘330 in view of Stubenrauch et al. This is a provisional double patenting rejection.
Claims 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-30, 32-36, and 40 of copending Application No. 18/308,290 (herein App ‘290) in view of Stubenrauch et al (supra).
App ‘290 claims antigen receptors comprising antigen binding moieties comprising a VH of SEQ ID NO: 8 (claim 21), which is 100% identical to instant SEQ ID NO: 8 (i.e., the limitations of instant claim 2):
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFSRYWMNWVRQAPGKGLEWVGEITPDSSTINY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFSRYWMNWVRQAPGKGLEWVGEITPDSSTINY 60
Qy 61 APSLKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARPYDYGAWFASWGQGTLVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 APSLKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARPYDYGAWFASWGQGTLVTVSS 119
And a VL of SEQ ID NO: 9 (claim 22), which is 100% identical to instant SEQ ID NO: 9 (i.e., the limitations of instant claim 3):
Qy 1 QAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTNKRAPGT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTNKRAPGT 60
Qy 61 PARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNHWVFGGGTKLTVL 109
|||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNHWVFGGGTKLTVL 109
App ‘397 claims these binding receptors comprise a TM domain as well (i.e., the limitations of instant claim 1; App ‘397 claim 1).
The instant invention was a prima facie obvious variant of App ‘397 in view of Stubenrauch et al. for the same reasons discussed for App ‘330 supra.. This is a provisional double patenting rejection.
Claims 1 and 4-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16, 18, 24-28, 34, and 35 of copending Application No. 18/417,644 (herein App ‘644) in view of Stubenrauch et al. (supra).
App ‘644 claims antigen binding receptors comprising anti-P329G binding domain comprising CDRH1-3 of SEQ ID NO: 1-3, respectively (claim 26), which are 100% identical to instant SEQ ID NO: 1-3, respectively. App ‘644 claims the anti-P329G binding domain comprising the LCDRH1-3 of SEQ ID NO: 4-6, which are 100% identical to instant SEQ ID NO: 4-6 (i.e., the limitations of instant claim 1).
The instant invention was a prima facie obvious variant of App ‘644 in view of Stubenrauch et al. for the same reasons discussed for App ‘330 supra.. This is a provisional double patenting rejection.
Claims 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-38 of copending Application No. 18/673,090 (herein App ‘090) in view of Stubenrauch et al. (supra).
App ‘090 claims antigen binding receptors comprising the amino acid sequence of SEQ ID NO: 129 (claims 1-3). SEQ ID NO: 129 comprises a VH that is 100% identical to instant SEQ ID NO: 8(i.e., the limitations of instant claim 2):
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFSRYWMNWVRQAPGKGLEWVGEITPDSSTINY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFSRYWMNWVRQAPGKGLEWVGEITPDSSTINY 60
Qy 61 APSLKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARPYDYGAWFASWGQGTLVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 APSLKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARPYDYGAWFASWGQGTLVTVSS 119
And a VL that is 100% identical to instant SEQ ID NO: 9 (i.e., the limitations of instant claim 3):
Qy 1 QAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTNKRAPGT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 140 QAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTNKRAPGT 60
Qy 61 PARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNHWVFGGGTKLTVL 109
|||||||||||||||||||||||||||||||||||||||||||||||||
Db 200 PARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNHWVFGGGTKLTVL 248
The invention encompassed by the instant claims was a prima facie obvious variant of the invention claimed by App ‘090 in view of Stubenrauch et al. for the same reasons discussed for App ‘330 supra. This is a provisional double patenting rejection.
Claims 1 and 4-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of copending Application No. 19/272,092 (herein App ‘092) in view of Stubenrauch et al. (U.S. PGPub 20200093860, supra).
App ‘092 claims antigen binding moieties comprising HCDR1-3 of SEQ ID NO: 11, 19, and 13 (claim 8), which are identical to instant SEQ ID NO: 1, 2, and 3, respectively. App ‘092 further claims LCDR1-3 of SEQ ID NO: 24-26 (claim 8), which are identical to instant SEQ ID NO: 4-6, respectively. App ‘092 further claims polypeptide complexes comprising the antigen binding moiety and a TM domain (i.e., the limitations of instant claim 1; App ‘092 claim 1).
The invention encompassed by the instant claims was a prima facie obvious variant of the invention claimed by App ‘092 in view of Stubenrauch et al. for the same reasons discussed for App ‘330 supra. This is a provisional double patenting rejection.
Claims 1-12 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-56 of copending Application No. 19/412,397 (herein App ‘397). Although the claims at issue are not identical, they are not patentably distinct from each other.
App ‘397 claims antigen receptors comprising antigen binding moieties comprising a VH of SEQ ID NO: 56 (claim 38), which is 100% identical to instant SEQ ID NO: 8 (i.e., the limitations of instant claim 2):
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFSRYWMNWVRQAPGKGLEWVGEITPDSSTINY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFTFSRYWMNWVRQAPGKGLEWVGEITPDSSTINY 60
Qy 61 APSLKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARPYDYGAWFASWGQGTLVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 APSLKGRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARPYDYGAWFASWGQGTLVTVSS 119
And a VL of SEQ ID NO: 60 (claim 39), which is 100% identical to instant SEQ ID NO: 9 (i.e., the limitations of instant claim 3):
Qy 1 QAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTNKRAPGT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QAVVTQEPSLTVSPGGTVTLTCRSSTGAVTTSNYANWVQEKPDHLFTGLIGGTNKRAPGT 60
Qy 61 PARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNHWVFGGGTKLTVL 109
|||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PARFSGSLLGGKAALTLSGAQPEDEAEYYCALWYSNHWVFGGGTKLTVL 109
App ‘397 claims these binding receptors comprise a TM domain as well (i.e., the limitations of instant claim 1; App ‘397 claim 37).
App ‘397 additionally claims the limitations of instant claim 4 (claim 40), claim 5 (claim 41), instant claim 6 (claim 42), instant claim 7 (claim 43), instant claim 8 (claim 44), instant claim 9 (claim 45), instant claim 10 (claim 46), instant claim 11 (claim 47), and instant claim 12 (claim 48).
The instant invention is anticipated by the invention claimed by App ‘397. This is a provisional double patenting rejection.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALEC JON PETERS whose telephone number is (703)756-5794. The examiner can normally be reached Monday-Friday 8:30am - 6:00pm EST.
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/ALEC JON PETERS/Examiner, Art Unit 1641
/MAHER M HADDAD/Primary Examiner, Art Unit 1641