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 .
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 5/1/2026, has been entered.
Claims 2-17 and 20-34 are pending.
Terminal Disclaimer
The terminal disclaimer filed on 2/3/2026, disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of pending reference application number 17/702,648 has been reviewed and is accepted. The terminal disclaimer has been recorded.
Withdrawal of Claim Rejections
Any previous rejection not reiterated herein has been withdrawn.
Claim Objections
Claims 17 and 33 are objected to because of the following informalities: Both claims appear to have typographical error where the term "of” appears to have been intended but only the letter “f” is present. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 16, 20, 32 and 34 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 16, 20, 32 and 34 recite “discrete molecule(s)”. The claims are indefinite because it is unclear whether a discrete molecule is the targeting agent or is derived from the targeting agent.
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.
Claim(s) 2-4, 6-7, 10-11, 16-17, 20-23, 26-27, 29 and 32-34 is/are rejected under 35 U.S.C. 103 as being unpatentable over Boghaert et al. (US 2007/0231333 A1).
Regarding claims 2 and 3, Boghaert et. al. discloses a therapeutic composition and method for the treatment of a cancer comprising administering an anti-human 5T4 antibody or antibody-drug conjugate (current claims 4 and 7), see paras. [0002] and [210], in combination with a second therapeutic agent. See para. [0024]. The anti-5T4 antibody of the invention may comprise a high energy radioisotope that is conjugated to the anti-5T4 antibody and that the anti-5T4 radioisotopes may be suitable for radiotherapy. See para. [121-122]. “Anti-5T4 antibodies and anti-5T4/drug conjugates of the invention may also be used in combination with other therapeutic antibodies and antibody/drug conjugates, including . . . antibodies and conjugates targeting a different antigen.” Para. [0215]. “Representative antibodies, which may be used alone or as an antibody/drug conjugate include . . . anti-CD33 antibodies . . . anti-HER2 antibodies . . . anti-CD47 antibodies” (current claim 6, 10, ). Para. [0215]. Further, Boghaert et. al. discloses that the conjugated radioisotope may be an alpha emitter or a beta emitter [0215].
Boghaert does not explicitly teach the method of treating cancer comprising a
radiolabeled anti-5T4 antibody in combination therapy, wherein the additional therapeutic agent
is the anti-CD47 antibody, and anti-SIRPa antibody, or a SIRPa Fc fusion protein.
It would have been prima facie obvious for a person of ordinary skill in the art prior to the effective filing date of the invention, to treat a mammalian subject having cancer with a combination of an anti-5T4 monoclonal antibody conjugated to a high energy radioisotope for the treatment of cancer as taught by Boghaert et. al. in combination with other therapeutic antibodies and antibody/drug conjugates targeting a different antigen as taught by Boghaert et. al., wherein the additional therapeutic agent is an anti-CD47 antibodies, anti-CD33 antibodies, or anti-HER2 antibodies as taught by Boghaert et. al. to benefit from the combination anti-cancer therapy as taught by Boghaert. This would have a reasonable expectation of success because Boghaert teaches the anti-cancer therapy benefits of radionuclide-conjugated 5T4 monoclonal antibodies and anti-CD47 antibodies, anti-CD33 antibodies, or anti-HER2 antibodies and an artisan would expect suitable anti-cancer benefits from using them in combination.
Regarding claim 7, the monoclonal antibody is an anti-5T4 antibody (current claims 17, 21, and 33), see paras. [0002], [0011], [0121-0122], and are "agents having anti-cancer activity in 5T4-expressing cells such as cancer cells from squamous/adenomatous lung carcinoma (non-small-cell lung carcinoma), invasive breast carcinoma, colorectal carcinoma, gastric carcinoma, squamous cervical carcinoma, invasive endometrial adenocarcinoma, invasive pancreas carcinoma, ovarian carcinoma, squamous vesical carcinoma, and choriocarcinoma" (current claims 10, 11, 16, 20, 23, 26, 27, 29, 32 and 34). See para. [0116].
Regarding claims 16, 20, 32 and 34, the anti-CD47 antibody is an additional therapeutic agent. See paras. [0211] and [0215] (reads on discrete molecule).
Regarding claim 22, “[c]ancers suitable for targeting using anti-5R4 anti-body/drug conjugates including 5T4-expressing primary and metastatic tumors in breast.” Para. [0190].
.
Claim(s) 5 is/are rejected under 35 U.S.C. 103 as being unpatentable over Boghaert et al. (US 2007/0231333 A1) as applied to claims 2-4, 6-7, 10-11, 16-17, 20-23, 26-27, 29 and 32-34 above, and further in view of ]Sandesh et al. (WO 2019027973) and Willingham et al. (US 20170210803).
The teachings of Boghaert et. al. in regards to claims 2 are in the 103 rejection above.
Boghaert discloses that radioisotopes that may be conjugated to the anti-5T4 antibody include 225-Actinium. See para. [0122]. Boghaert et. al. also teaches that "an effective dose will be in the range from about 0.01 mg/m² to about 50 mg/m², such as from about 0.1 mg/m² to about 20 mg/m², or about 15 mg/m², which dose is calculated based on the amount of anti-5T4 antibody. For a radiolabeled anti-5T4 antibody, an effective dose is typically in the range from about 1 mCi to about 300 mCi, normally about 5 mCi to 100 mCi, depending on the radioisotope and the binding affinity of the antibody" [0207].
Boghaert does not explicitly disclose that a radiation dose of 0.1-2.0 µCi/kg body weight of the subject and a protein dose of 0.1-5.0mg/kg body weight of the subject and wherein the CD47 blockade is administered at a total dose of 0.05-5.0 mg/kg body weight of the subject.
This deficiency is partially resolved by Sandesh et. al. which teaches a radionuclide labelled monoclonal antibody and teaches an effective amount of the labeled antibody comprises a radiation dose of 0.1 to 10 0.1-2.0 µCi/kg body weight of the subject, see para. [0130], and at dose ranges selected from a group including 1ug/kg to 1mg/kg. See paras. [0129] and [0134].
It would have been obvious for a person of ordinary skill in the art, before the effective filing date, to use the dosing schedule of Sandesh et. al. to modify the composition of Boghaert for the purpose of developing an effective does comprising a radiolabeled antibody and a protein concentration specific to the subject. This would have a predictable effect because both Boghaert and Sandesh et. al. teach radiolabeled therapeutic monoclonal antibodies.
Boghaert et. al. in view of Sandesh et. al. does not teach that the CD47 blockade is administered at a total dose of 0.05-5.0 mg/kg body weight of the subject.
However, Willingham et. al. teaches combination treatments of CD47 blockade in combination with an immunomodulatory anti-cancer therapy, see Abstract and para. [0115], wherein the therapeutic dosage may be about 0.01 to about 5mg/kg of the host body weight. See para. [0120]. Example dosages can be 1 mg/kg body weight or 10 mg/kg body weight with the range of 1-10 mg/kg. See para. [120].
It would have been prima facie obvious for a person of ordinary skill in the art, before the effective filing date, to optimize the anti-CD47 blockade dose within the disclosed preferred range of about 0.1 to about 5mg/kg or 1-10mg/kg body weight in a combination therapy with a second monoclonal antibody in order to determine the effective dose in combination with a second antibody at less than 1mg/kg body weight to predictable effect because both Boghaert and Willingham teach combination antibody therapies comprising anti-CD47 antibodies. See MPEP $2144.05.
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 2-4, 8-9, 12-15, 21, 24-25 and 30-31 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 and 19-22 of copending Application No. 17/726,296 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the instant claims anticipate some of the claims of the reference application and visa-versa.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ROBERT S CABRAL whose telephone number is (571)270-3769. The examiner can normally be reached M-F 8 am - 5 pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Ali Soroush can be reached at 571-272-9925. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/ROBERT S CABRAL/Primary Examiner, Art Unit 1614
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