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 .
DETAILED ACTION
Applicant’s election without traverse of Group I, claims 1-17, 19-22, and 25-27 in the reply filed on 11/25/2025 is acknowledged. Applicant also elected 1) CEA as a tumor antigen, 2) the first light chain of SEQ ID NO: 99, which comprises the VL of SEQ ID NO: 80, a second light chain of SEQ ID NO: 22, which comprises the VL of SEQ ID NO: 19, which comprises the LCDRs 1-3 of SEQ ID NO(s): 14-16, respectively.
Claims 1-17, 22-27, and 29-31 are pending.
Claims 8-11 and 15 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.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 11/25/2025. With respect to claim 15, it is noted that the elected anti-CD28 light chain CDRs of SEQ ID NO(s): 23-25, respectively, are comprised within a kappa light chain, according to [0122] of the specification.
Claims 23 and 24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/25/2025.
Claims 1, 4, 5, 9, 11-13, 25, and 26 are currently amended.
Claims 18-21 and 28 are canceled.
Claims 29-31 are newly added.
Claims 1-7, 12-14, 16, 17, 22, 25-27, and 29-31 are under examination on the merits.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Claims 1-7, 12-14, 16, 17, 22, 25-27, and 29-31 have an effective filing date of 03/07/2022, corresponding to PRO 63/317,491.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 05/03/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Rejections
35 U.S.C. 112(a)
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 1-4, 12-14, 16, 17, and 22 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Claim 1 is drawn to a second antigen binding domain that binds a tumor-associated antigen (TAA), wherein the second antigen binding domain comprises the HCDRs 1-3 of SEQ ID NO(s): 1-3, respectively. As indicated above, the elected TAA is carcinoembryonic antigen (CEA). Therefore the claim is drawn to a genus of anti-CEA antibodies that comprise the HCDRs 1-3 of SEQ ID NO(s): 1-3, respectively, and any LCDR sequences. Various LCDRs that may be paired with the HCDRs 1-3 of SEQ ID NO(s): 1-3, respectively, are provided in claim 5, which provides 3 LCDR sets that may be paired with the HCDRs 1-3 of SEQ ID NO(s): 1-3, respectively, in order to arrive at an antigen binding domain capable of binding CEA. Even though Applicant has disclosed three species within the claimed genus, the specification does not provide adequate written description for the entire claimed genus, because one skilled in the art would be unable to immediately envision, recognize, or distinguish at least most of the members comprised within the genus claimed, specifically, which light chain CDR sequences may be paired with the HCDRs 1-3 of SEQ ID NO(s): 1-3, respectively, such that a resultant antigen binding domain is capable of binding CEA. As detailed below Applicant’s disclosure is not sufficient to demonstrate possession of the entire claimed genus, and as such Applicant’s disclosure does not satisfy the written description requirement of 35 U.S.C. 112(a).
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
PNG
media_image1.png
18
19
media_image1.png
Greyscale
A “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. In the instant case, Applicant has disclosed three species within the genus claimed; however given the substantial antibody structure variation within the genus, as well as the high level of unpredictability in the art, the disclosure of three species comprised within the claimed genus is not sufficiently representative of the entire genus.
Furthermore Applicant has not disclosed relevant, identifying characteristics of CDR region amino acid sequences (or combinations thereof) that confer upon an antibody the ability to bind CEA, because the instant specification does not provide structural antibody features that correlate with a functional ability to bind CEA. To elaborate on why the claimed antibodies lack adequate written description, Mariuzza (Annu. Rev. Biophys. Biophys. Chem., 16: 139-159, 1987) reviews the structural basis of antigen antibody recognition and teach that naturally occurring conventional antibodies comprise two polypeptides, the so-called light and heavy chains. The antigen combining site of an antibody is a three-dimensional structure that fully comprises six CDRs, three each from the light and heavy chains. The amino acid sequences of the CDRs are hypervariable, as the amino acid residues contained within the CDRs determine much of the antibody’s antigen binding specificity. In view of Mariuzza, it is apparent that antibodies having less than all six CDRs that form the antigen binding site of a conventional antibody in their proper context of heavy and light chain variable domains do not describe the particularly identifying structural feature of the antibody that correlates with the antibody’s ability to bind antigen. Absent a description of the at least minimal structural features correlating with a functional ability to bind CEA which are shared by members of a genus commonly sharing this function, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish which light chain CDR sequences may be paired with the HCDRs 1-3 of SEQ ID NO(s): 1-3, respectively, such that a resultant antigen binding domain is capable of binding CEA.
Although screening techniques can be used to isolate light chain CDR sequences that may be paired with the HCDRs 1-3 of SEQ ID NO(s): 1-3, respectively, such that a resultant antigen binding domain is capable of binding CEA, Applicant is reminded that the written description requirement of 35 U.S.C. 112 is severable from the enablement provision. As stated in Vas-Cath Inc. v. Mahurkar (CA FC) 19 USPQ2d 1111, 935 F2d 1555, “The purpose of the ‘written description’ requirement is broader than to merely explain how to ‘make and use’; the applicant must also convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.”
Accordingly given the lack of particularity with which the claimed anti-CEA antibodies are described in the specification, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish at least most of the members of the genus to which the claims are directed, and therefore the specification would not reasonably convey to the skilled artisan that Applicant was in possession of the claimed invention at the time the application was filed.
Nonstatutory 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 1-7, 12-14, 16, 17, 22, 25-27, and 29-31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4 of copending Application No. 18/825,304 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
With respect to the instant claims 1, 4, 5, 22, 25, and 29, conflicting claim 1 recites a bispecific antibody comprising 1) an anti-CD28 binding domain that comprises the HCDRs 1-3 of SEQ ID NO(s): 1-3, respectively, which shares 100% sequence homology with the instant HCDRs 1-3 of SEQ ID NO(s): 1-3, and the LCDRs 1-3 of SEQ ID NO(s): 18, WAS, and 20, respectively, which shares 100% sequence homology with the instant LCDRs 1-3 of SEQ ID NO(s): 23, WAS (SEQ ID NO: 24), and 25, and 2) an anti-CEA binding domain that comprises the HCDRs 1-3 of SEQ ID NO(s): 1-3, respectively, which shares 100% sequence homology with the instant HCDRs 1-3 of SEQ ID NO(s): 1-3, and the LCDRs 1-3 of SEQ ID NO(s): 11-13, respectively, which shares 100% sequence homology with the instant LCDRs 1-3 of SEQ ID NO(s): 14-16.
With respect to claims 2, 6, 12, 14, and 30, conflicting claim 3 recites 1) an anti-CD28 antigen binding domain that comprises the VL of SEQ ID NO: 24, which shares 100% sequence homology with the instant SEQ ID NO: 80 (kappa light chain according to [0122] of the specification), and the VH of SEQ ID NO: 4, which shares 100% sequence homology with the instant SEQ ID NO: 4, and 2) an anti-CEA antigen binding domain that comprises the VL of SEQ ID NO: 15, which shares 100% sequence homology with the instant SEQ ID NO: 19 (lambda light chain according to [0122] of the specification), and the VH of SEQ ID NO: 4, which shares 100% sequence homology with the instant SEQ ID NO: 4.
With respect to claim 3, conflicting claim 4 recites an anti-CD28 antibody that comprises the light chain of SEQ ID NO: 26, which shares 100% sequence homology with the instant SEQ ID NO: 99.
With respect to claim 7, conflicting claim 4 recites an anti-CEA antibody that comprises the heavy chain of SEQ ID NO: 17, which shares 100% sequence homology with the instant SEQ ID NO: 22.
With respect to claim 13, 16, and 17, conflicting claim 4 recites an anti-CEA antibody that comprises the heavy chain of SEQ ID NO: 7, which comprises SEQ ID NO: 4, as recited in conflicting claim 4. Conflicting SEQ ID NO: 7 shares 100% sequence homology with the instant SEQ ID NO: 7. At Table 1 of the specification for the conflicting claims, it is disclosed that SEQ ID NO: 7 is a heavy chain that comprises LALAPA mutations.
With respect to claim 26, given that conflicting claim 2 recites a bispecific antibody but does not specify that said bispecific antibody comprises an Fc region, it is submitted that the bispecific antibody of claim 2 at least encompasses one or more of F(ab) fragments, F(ab’)2 fragments, and Fv fragments.
Claim 27 is included in this rejection, because a traditional anti-CEA/anti-CD28 bispecific antibody would generally comprise two antigen binding sites, a monovalent anti-CEA antigen binding site and a monovalent anti-CD28 antigen binding site.
With respect to claim 31, conflicting claim 4 recites an anti-CEA antibody that comprises the heavy chain of SEQ ID NO: 7, which shares 100% sequence homology with the instant SEQ ID NO: 7; conflicting claim 4 recites an anti-CD28 antibody that comprises the light chain of SEQ ID NO: 26, which shares 100% sequence homology with the instant SEQ ID NO: 99; and conflicting claim 4 recites an anti-CEA antibody that comprises the heavy chain of SEQ ID NO: 17, which shares 100% sequence homology with the instant SEQ ID NO: 22.
This is a provisional nonstatutory double patenting rejection.
Claims 25-27 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 2 of copending Application No. 18/491,130 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other.
With respect to the instant claim 25, conflicting claims 1 and 2 recite a bispecific antibody comprising an anti-CD28 binding domain that comprises the HCDRs 1-3 of SEQ ID NO(s): 6-8, respectively, which shares 100% sequence homology with the instant HCDRs 1-3 of SEQ ID NO(s): 1-3, and the LCDRs 1-3 of SEQ ID NO(s): 18, WAS, and 20, respectively, which shares 100% sequence homology with the instant LCDRs 1-3 of SEQ ID NO(s): 23, WAS, and 25.
With respect to claim 26, given that conflicting claims 1 and 2 recite a bispecific antibody but does not specify that said bispecific antibody comprises an Fc region, it is submitted that the bispecific antibody of claim 2 at least encompasses one or more of F(ab) fragments, F(ab’)2 fragments, and Fv fragments.
Claim 27 is included in this rejection, because a traditional anti-PD-L1/anti-CD28 bispecific antibody would generally comprise two antigen binding sites, a monovalent anti-PD-L1 antigen binding site and a monovalent anti-CD28 antigen binding site.
This is a provisional nonstatutory double patenting rejection.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NELSON B MOSELEY II whose telephone number is (571)272-6221. The examiner can normally be reached on M-F, 9:00-6:00 EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis, can be reached at 571-270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642