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
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 8, 2025 has been entered. By way of this submission, Applicant has amended claims 1, 52, and 69, and cancelled claims 3, 22, 67, and 68.
Claims 1-2, 52, 55-60, and 69-73 are currently pending in the application. Claims 58-60 remain withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 with traverse in the reply filed on September 22, 2021.
Claims 1-2, 52, 55-57, and 69-73 are therefore under examination before the Office.
The rejections of record can be found in the previous Office action, dated April 8, 2025.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on October 8, 2025 was filed after the mailing date of the first Office action on the merits on November 2, 2021. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Claim Objections
Claim 1 is objected to because of the following informalities: there appears to be an extra word at line 13: “wherein and the first and second antibody…”. Appropriate correction is required.
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.
Claim Rejections - 35 USC § 102
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)(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.
Claims 1-2, 52, 55-57, 69, and 72-73 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Chang (U.S. patent 11,834,506). This is a new grounds of rejection.
Chang teaches a multi-specific binding protein comprising:
(a) a first antigen-binding site that binds and activates human NKG2D;
(b) a second antigen-binding site that binds a tumor-associated antigen; and
(c) a first antibody Fc domain of human IgG1 and a second antibody Fc domain of human IgG1 that together are sufficient to bind CD16, wherein the first and second antibody Fc domains comprise different amino acid mutations to promote heterodimerization, and the first and second antibody Fc domains each comprise an N-terminus,
wherein the first antigen-binding site is linked to the N-terminus of the first antibody Fc domain, and the second antigen-binding site is linked to the N-terminus of the second antibody Fc domain (claim 1).
Chang further teaches that the tumor antigen may be CD19 (col. 2, line 52).
Chang further teaches that the antigen-binding sites may be Fab (Figure 2) or scFv (col. 2, lines 44-46).
Chang further teaches that the binding of the above molecule increases levels of CD107a and interferon gamma (Figure 45).
Chang further teaches that the first antigen-binding site binds to NKG2D in humans and cynomolgus monkeys (col. 2, lines 22-24).
Chang further teaches that antibody Fc domain comprises hinge and CH2 domains (col. 10, line 15).
Chang further teaches substitutions in the human IgG1 constant region such as K360E, K409W, Q347R, D399V and F405T (col. 20, lines 2-18).
Chang further teaches a cell comprising one or more nucleic acids encoding the above protein (claim 14).
Chang further teaches a formulation comprising the multi-specific binding protein above and a pharmaceutically acceptable carrier (claim 13).
Chang further teaches sequences of the anti-NKG2D binding site of SEQ ID NOs: 41-48 (ADI-27727) which are identical to Applicant’s SEQ ID NOs: 41-48, which is pertinent to claims 72-73.
Applicant is invited to file a statement according to 35 U.S.C. 102(b)(2)(C) and MPEP 717.02 and 2154.02(c) in order to assist in addressing this rejection.
Claim Rejections - 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
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.
Claims 1, 3, 22,52, 55-57, 67-68, and 70-71 were previously rejected under 35 U.S.C. 103 as being unpatentable over Gauthier (WO2016207273A2) in view of Kufer (US20040038339A1) and Loew (US20170368169A1).
Claim 2 was previously rejected under 35 U.S.C. 103 as being unpatentable over Gauthier (WO2016207273A2) in view of Kufer (US20040038339A1) and Loew (US20170368169A1) as applied to claim 1 above, and further in view of Steigerwald (MAbs. Mar-Apr 2009; 1(2):115-27).
Claim 69 was previously rejected under 35 U.S.C. 103 as being unpatentable over Gauthier (WO2016207273A2) in view of Kufer (US20040038339A1) and Loew (US20170368169A1) as applied to claim 1 above, and further in view of Ha (Front Immunol. 2016; 7:394).
Claim 73 was previously rejected under 35 U.S.C. 103 as being unpatentable over Gauthier (WO2016207273A2) in view of Kufer (US20040038339A1) and Loew (US20170368169A1) as applied to claim 1 above, and further in view of Urso (U.S. patent 7,879,985).
Applicant argues that a person of ordinary skill would not expect the claimed product to yield the unexpected benefits of improved functionality in killing cancer cells. Applicant presents Declarations under Rule 37 CFR 1.132 from Dr. Lewis L. Lanier and Dr. Nikhil Joshi in support of these arguments.
Applicant's arguments in view of the amendments to the claims and the Declarations under 37 CFR 1.132 from Dr. Lewis L. Lanier and Dr. Nikhil Joshi are persuasive, and the above rejections are hereby withdrawn.
Claims 70-71 are rejected under 35 U.S.C. 103 as being unpatentable over Chang as applied to claim 1 above, and further in view of Gauthier (WO2016207273A2). This is a new grounds of rejection.
The teachings of Chang have been discussed supra. However, Chang does not teach the claimed sequences of the anti-CD19 binding domain.
Gauthier teaches proteins possessing two antigen binding domains each formed by immunoglobulin variable regions, thereby binding to two different antigens, and a dimeric Fc domain that binds CD16 (page 2, lines 26-33).
Gauthier further teaches that the two antigen binding domains may bind to an activating receptor on an immune effector cell such as NKG2D and a cancer antigen such as CD19 (page 16, lines 9-29, Example 3, and Figure 2D, Format 5).
Gauthier also teaches the elected sequences of the instant application’s SEQ ID NSs: 175 and 179 as Gauthier’s SEQ ID NOs: 6 and 4, respectively. Applicant’s SEQ ID Nos: 175 and 179 complete encompass the elected CDRs of claim 70 (see the Office action dated March 11, 2022 at page 2 and the Office action dated July 29, 2022 at page 7), which is pertinent to claims 70 and 71.
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of Chang and Gauthier to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both Chang and Gauthier are drawn to multispecific antibodies that bind NKG2D, CD19, and CD16. Starting with the molecule of Chang, one of ordinary skill could apply the known sequences recited in Gauthier into the anti-CD19 site by simple substitution. Each component of the combination would perform its known, usual function to affect a predictable result.
Applicant is invited to file a statement according to 35 U.S.C. 102(b)(2)(C) and MPEP 717.02 and 2154.02(c) regarding Chang in order to assist in addressing this 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 1-3, 9, 22,52, and 55-57 were previously provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 11-16, 18, 20-24 of copending Application No. 16/483,330 (reference application) in view of Loew.
Claims 1-3, 9, 22,52, and 55-57 were previously provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 31, and 34-35 of copending Application No. 16/967,218 (reference application) in view of Loew.
Applicant's amendments to the claims have addressed these issues, and the above rejections are hereby withdrawn.
Claims 1-2, 52, 55-57, and 69-73 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 and 13-14 of U.S patent No. 11,834,506 in view of Gauthier. This is a new grounds of rejection.
The '506 patent claims a multi-specific binding protein comprising:
(a) a first antigen-binding site that binds and activates human NKG2D;
(b) a second antigen-binding site that binds a tumor-associated antigen; and
(c) a first antibody Fc domain of human IgG1 and a second antibody Fc domain of human IgG1 that together are sufficient to bind CD16;
wherein the first antigen-binding site is linked to the N-terminus of the first antibody Fc domain, and the second antigen-binding site is linked to the N-terminus of the second antibody Fc domain (claim 1).
The '506 patent also claims the above protein comprises a portion of an antibody Fc domain sufficient to bind CD16, wherein the antibody Fc domain comprises hinge and CH2 domains (claim 7).
The '506 patent also claims sequences of the NKG2D-binding domain that are identical to those recited in Applicant’s claims 72-73 (claim 8).
The claims of the '506 patent differ from the instant claims in that the '506 patent does not claim CD19 as a specific tumor antigen.
Gauthier teaches proteins possessing two antigen binding domains each formed by immunoglobulin variable regions, thereby binding to two different antigens, and a dimeric Fc domain that binds CD16 (page 2, lines 26-33).
Gauthier further teaches that the two antigen binding domains may bind to an activating receptor on an immune effector cell such as NKG2D and a cancer antigen such as CD19 (page 16, lines 9-29, Example 3, and Figure 2D, Format 5).
Gauthier also teaches the elected sequences of the instant application’s SEQ ID NSs: 175 and 179 as Gauthier’s SEQ ID NOs: 6 and 4, respectively. Applicant’s SEQ ID Nos: 175 and 179 complete encompass the elected CDRs of claim 70 (see the Office action dated March 11, 2022 at page 2 and the Office action dated July 29, 2022 at page 7), which is pertinent to claims 70 and 71.
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of the ‘506 patent and Gauthier to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both the ‘506 patent and Gauthier are drawn to multispecific antibodies that bind NKG2D, a cancer antigen, and CD16. Starting with the molecule of the ‘506 patent, one of ordinary skill could apply the known sequences recited in Gauthier into the anti-CD19 site by simple substitution. Each component of the combination would perform its known, usual function to affect a predictable result.
Claims 1-3, 9, 22,52, and 55-57 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 4-6 of U.S. patent No. 12,384,847 (formerly copending Application No. 16/967,218) in view of Gauthier. This is a new grounds of rejection.
The '847 patent claims a method of enhancing tumor cell death directly or indirectly, the method comprising exposing a tumor cell and a natural killer cell to a multi-specific binding protein comprising:
(a) a first antigen-binding site that binds and activates human NKG2D;
(b) a second antigen-binding site that binds a tumor-associated antigen; and
(c) a first antibody Fc domain of human IgG1 and a second antibody Fc domain of human IgG1that together bind CD16, wherein the first and second antibody Fc domains comprise different amino acid mutations to promote heterodimerization, and the first and second antibody Fc domains each comprise an N-terminus,
wherein the first antigen-binding site is linked to the N-terminus of the first antibody Fc domain, and the second antigen-binding site is linked to the N-terminus of the second antibody Fc domain (claim 1).
The claims of the '847 patent differ from the instant claims in that the '847 patent does not claim CD19 as a specific tumor antigen.
Gauthier teaches proteins possessing two antigen binding domains each formed by immunoglobulin variable regions, thereby binding to two different antigens, and a dimeric Fc domain that binds CD16 (page 2, lines 26-33).
Gauthier further teaches that the two antigen binding domains may bind to an activating receptor on an immune effector cell such as NKG2D and a cancer antigen such as CD19 (page 16, lines 9-29, Example 3, and Figure 2D, Format 5).
Gauthier also teaches the elected sequences of the instant application’s SEQ ID NSs: 175 and 179 as Gauthier’s SEQ ID NOs: 6 and 4, respectively. Applicant’s SEQ ID Nos: 175 and 179 complete encompass the elected CDRs of claim 70 (see the Office action dated March 11, 2022 at page 2 and the Office action dated July 29, 2022 at page 7), which is pertinent to claims 70 and 71.
It would have been prima facie obvious for a person of ordinary skill in the art as of the effective filing date to combine the teachings of the ‘847 patent and Gauthier to arrive at the claimed invention. An ordinary artisan would have been motivated to do so, and have a reasonable expectation of success, since both the ‘847 patent and Gauthier are drawn to multispecific antibodies that bind NKG2D, a cancer antigen, and CD16. Starting with the molecule of the ‘847 patent, one of ordinary skill could apply the known sequences recited in Gauthier into the anti-CD19 site by simple substitution. Each component of the combination would perform its known, usual function to affect a predictable result.
Claim 1-2, 55-57, and 69-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 21, 29-34, 39, and 41-43 of copending Application No. 18/482,629. This is a new grounds of rejection.
The '629 application claims a cell comprising one or more nucleic acids encoding a multi-specific binding protein comprising:
(a) a first antigen-binding site that binds human NKG2D;
(b) a second antigen-binding site that binds a tumor-associated antigen; and
(c) a first antibody Fc domain and a second antibody Fc domain each of human IgG1 isotype that together are sufficient to bind human CD16, wherein the first and second antibody Fc domains comprise different amino acid mutations to promote heterodimerization (claim 21).
The '629 application further claims that the first antigen-binding site binds to NKG2D in humans and non-human primates (claim 29), and comprises sequences identical to those of the instantly claimed invention (claim 34).
The '629 application further claims that the first and second antibody Fc domains each comprise an N-terminus, the first antigen-binding site is linked to the N-terminus of the first antibody Fc domain, and the second antigen-binding site is linked to the N-terminus of the second antibody Fc domain (claim 39).
The '629 application further claims that the amino acid sequence of the first antibody Fc domain differs from the amino acid sequence of an antibody Fc domain of human IgGI by K360E and K409W substitutions, and the amino acid sequence of the second antibody Fc domain differs from the amino acid sequence of an antibody Fc domain of human IgG1 by Q347R, D399V and F405T substitutions (claim 41).
The 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 PETER JOHANSEN whose telephone number is (571)272-0280. The examiner can normally be reached Monday-Friday, 8:00 to 4:00.
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, Daniel Kolker can be reached at (571) 272-3181. 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.
/PETER JOHANSEN/Examiner, Art Unit 1644