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 .
Priority
This application is a CON of PCT/IB2019/001292 12/03/2019, PCT/IB2019/001292 has PRO 62/774,847 12/03/2018.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/16/2025 was filed in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Status of claims
Claims 34-48 are pending in this application and are objected or rejected to for the reasons set forth below. Claims 1-33 are cancelled. Claims 41-47 are withdrawn.
Applicant’s arguments, filed 07/16/2025, have been fully considered. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. They constitute the complete set presently being applied to the instant application. Claims 34-40 and 48 are currently under examination.
The obviousness rejection below is repeated from the 04/16/2025 Office Action and modified in order to address the most recent arguments.
Specification
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
Applicant is reminded of the proper content of an abstract of the disclosure.
In chemical patent abstracts for compounds or compositions, the general nature of the compound or composition should be given as well as its use, e.g., “The compounds are of the class of alkyl benzene sulfonyl ureas, useful as oral anti-diabetics.” Exemplification of a species could be illustrative of members of the class. For processes, the type of reaction, reagents and process conditions should be stated, generally illustrated by a single example unless variations are necessary.
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 of the disclosure is objected to because the current wording of the abstract, “Combination therapies comprising administering radioimmunoconjugates and DNA damage response inhibitors.”, does not indicate what the invention is administered for. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
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 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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 34-40 and 48 rejected under 35 U.S.C. 103 as being unpatentable over Burak (U.S. Patent 10,093,741 Bl) in view of Hsiao (U.S. Patent 10,100,017 B2).
The instant claims are directed to a method for treating or ameliorating cancer, comprising:
(i) administering to a mammal a radioimmunoconjugate, wherein the mammal has received or is receiving the DNA damage response inhibitor (DDRi) Olaparib;
(ii) administering to a mammal a DDRi, wherein the mammal has received or is receiving a radioimmunoconjugate; or
(iii) administering to the mammal the DDRi Olaparib at the same time as administering the mammal a radioimmunoconjugate. Wherein AVE1642 is the antibody or antigen-binding fragment capable of binding to IGF-IR and the radionuclide is Actinium-225 (225Ac).
Burak et al. teach a structure of a radioimmunoconjugate which shares the same structural connectivity’s as in the instant application (col. 4 bottom). Burak also teaches that the radioimmunoconjugate comprises 225Ac as an alpha emitting radionuclide ( col. 5, lines 10-12). Furthermore Burak reveals the same AVE1642 IGF-lR antibody, including the same SEQ ID's (sequence Identification) as the Instant application (col. 28, lines 1-66). Burak cites that the radioimmunoconjugate formula cites "B" as an attachment site for a therapeutic or targeting moiety wherein an antibody or antigen-binding fragment is an insulin-like growth factor receptor-1 (IGF-lR) including AVE1642 (col. 2, lines 55-64). Burak also teaches an embodiment in which the invention is used for the treatment of solid or liquid cancers including breast, pancreatic, head and neck, Ewing’s sarcoma and multiple myeloma (col. 5, lines 30-54). Burak also teaches that the conjugates of the invention can be used in combination with other conventional methods of treatment or therapies ( col. 36, lines 1-13).
However, Burak et al. fail to disclose the combined use of the DNA damage response inhibitor (DDRi) Olaparib in a combination treatment for cancer.
Hsiao et al. teach the compound of 4-[(3-[(4-cyclopropylcarbonyl)piperazin-l-yl] carbonyl)-4-fluorophenyl]methyl(2H)phthalazin-l-one (Olaparib) as a poly ADP ribose polymerase (PARP) inhibitor useful in the treatment of cancers (abstract). Hsiao also teaches that Olaparib is useful in the treatment of breast and prostate cancers (col. 11, lines 24-32).
Hsiao does not teach an antibody or antigen-binding fragment capable of binding to IGF-IR or a radionuclide.
Therefore, it would have been prima facie obvious to a person having ordinary skill in the art (PHOSITA), prior to the effective filing date of the claimed invention, to combine the use of the DDRi PARP inhibitor (Olaparib) in a combination cancer therapy as taught by Hsiao in a combination therapy with a radioimmunoconjugate comprising 225Ac as taught by Burak. It would have been prima facie obvious to combine two compositions known for treatment of breast cancer in order to form a third compositions for the treatment of breast cancer. See MPEP 2144.06.
A PHOSITA would have had a reasonable expectation of success in treating breast cancer, as well as other cancer types by following the teachings of Burak and Hsiao. See MPEP 2144.06 Art Recognized Equivalence for the Same Purpose.
Obviousness Remarks
Applicants argue “the Office erroneously concludes that it is prima facie obvious ‘to use DDRi PARP inhibitor Olaparib in combination therapy with a radioimmunoconjugate comprising 225Ac and an IGF-1R antibody or antigen of AVE1642.” This argument is found unpersuasive because MPEP 2144.06 expressly teaches that "[i]t is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." Citing In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Here, the compositions of Burak and Hsiao are each individually taught for treatment of cancer, and more specifically breast cancer. Thus, it would have been prima facie obvious to combine them for the treatment of breast cancer.
Applicants argue that they have overcome any prima facie case of obviousness by demonstrating the unexpected and surprising result that the administration of the radioimmunoconjugate instantly claimed and both BAY-1895344 and Olaparib. Specifically, Applicants allege that the reduction in tumor volumes in mammals administered reductions in tumor volumes in mammals being co-administered the radioimmunoconjugate and the DDRi were significantly greater than that seen in mammals treated with either the radioimmuno-conjugate or the DDRi inhibitor alone.” Example 2 of the instant application demonstrates that when 225Ac-FPI-1434 and BAY-1895344 were administered as a combination therapy animals demonstrated significantly lower tumor volumes when compared with either treatment alone. Example 6 of the instant application demonstrates that the combination of 225Ac-FPI-1434 Olaparib, both at lower effective doses, resulted in synergistic efficacy. Examiner does not find the argument to be persuasive. Example 2 appears to show a near additive effect despite the combination group receiving a larger initial dose of BAY-1895344. A skilled artisan administering two known treatments would have a reasonable expectation of an additive effect. Thus, with regard to example 2, Applicants have not met their burden of demonstrating unexpected result sufficient to overcome the prima facie case of obviousness. See MPEP 716. Similar to Example 2, Example 6 demonstrates that a combination dosage shows decreased tumor volume. However, Applicants have not explained why they believe the data set to demonstrate synergy. MPEP 716.02 requires Applicants to explain the proffered data. 716.02(b)(2). It also requires Applicants to place the claims commensurate in scope with the unexpected results. MPEP 716.02(d). Here, Applicants have not explained which data points they believe to demonstrate synergy, and have not placed the claims commensurate in scope with that data. Examiner notes that any potential synergy would be for treating a mammal using a specific combination dose and form of administration. The present claims do note limit the subject, dose or administration. Since Applicants have not met their burden of overcoming the prima facie case of obviousness, the obviousness rejection is maintained.
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 Langi, 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 CPR l.32l(c) or l.32l(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 CPR l.32l(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. l.
For a reply to a non-final Office action, see 37 CPR 1.11 l(a). For a reply to final Office action,
see 37 CPR 1.113( c ). A request for reconsideration while not provided for in 37 CPR 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 autoprocessed and approved immediately upon submission. For more information about eTerminal
Disclaimers, refer to www. uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 34-37 and 48, are rejected on the ground of nonstatutory double patenting
as being unpatentable over claims 1-10, 13-17, 19-20, 23-24 and 28-40 of U.S. Patent
US 11,433,148 B2 (to Burak) in view of Hsiao (U.S. Pat US 10,100,017 B2).
The referenced claims teaches a radioimmunoconjugate structure, use of the radionuclide
225Ac, and the antibody or antigen-binding fragment capable of binding to IGF-lR is AVE1642
which has the same complementarity determining region (CDR) and used in the treatment of
cancer in mammals.
The referenced claims do not explicitly teach the use of the DNA damage response
inhibitor (DDRi), Olaparib, which is a ADP ribose polymerase (PARP) inhibitor.
Hsiao Discloses the ADP ribose polymerase (PARP) inhibitor of Olaparib, used for the
treatment of cancers including breast and prostate inhibitors (Col. 2, lines 1-13).
Therefore, it would have been prima facie obvious to a person of ordinary skill in the art,
prior to the effective filing date of the claimed invention, to use the DDRi PARP inhibitor
Olaparib in a combination therapy with a radioimmunoconjugate comprising 225Ac and an IGF-1R antibody or antigen of AVE1642.
A person of ordinary skill in the art would have been motivated to use Olaparib taught by
Hsiao in a combination therapy with the radioimmunoconjugate using 225Ac and AVE1642
taught by Burak because they both are used in the treatment of cancers including breast and
prostate cancer. Therefore, based on the current record the invention as a whole is prima facie
obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the
references, especially in the absence of evidence to the contrary.
Double Patenting Remarks
Applicant's request that the double patenting rejections be held in abeyance until such time that otherwise allowable subject matter is identified. Accordingly, the pending double patenting rejections are maintained.
Conclusion
All claims are rejected. No claims are currently allowable.
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERNESTO VALLE JR whose telephone number is (703)756-5356. The examiner can normally be reached 0730-1700 M-F EST, 1st Friday off.
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, Adam C Milligan can be reached at 571-270-7674. 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.
/E.V./Examiner, Art Unit 1623
/ADAM C MILLIGAN/ Supervisory Patent Examiner, Art Unit 1623