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 .
Status of the Claims
Claims 1 - 20 were pending. No claim has been amended, canceled, or newly added. Claims 1 – 20 are currently pending and are the subject of this Office Action.
Claim Rejections - 35 USC § 103
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.
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.
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.
Previous rejection, maintained: claims 1 – 20 are rejected under 35 U.S.C. 103 as being unpatentable over DE GOEIJ (US 20130189271 A1, published 07/25/2013, see PTO-892: Notice of References Cited of 05/19/2025).
The present application is directed to a method of treating a p185her2/neu-associated tumor in a subject comprising administering to the subject a therapeutically effective amount of a first anti-p185her2/neu antibody or an antigen binding portion thereof, a second anti- p185her2/neu antibody or an antigen binding portion thereof, and interferon-gamma (IFNγ).
“[A] first anti-p185her2/neu antibody” of independent claims 1 and 10 is further limited to trastuzumab in claims 3 and 12 or further limited to pertuzumab in claims 5 and 14 and are thus examined accordingly. “[A] second anti- p185her2/neu antibody” of independent claims 1 and 10 is further limited to pertuzumab in claims 4 and 13 and are thus examined accordingly.
Also, the present specification defines p185her2/neu to also be known as erbB2 (p. 1, lines 34 – 35).
DE GOEIJ is directed to isolated monoclonal antibodies which bind to human epidermal growth factor receptor 2 (HER2) for the treatment of cancer. See abstract and paragraphs 0001, 0009, and 0011. DE GOEIJ discloses that an inhibitor of ErbB2 (HER2/neu) is a HER2 antibody, e.g. trastuzumab, trastuzumab-DM1 or pertuzumab. See paragraph 440. DE GOEIJ teaches that the complementary mechanisms of action of pertuzumab and trastuzumab results in an enhanced anti-tumor effects and efficacy when combined in patients who progressed during prior trastuzumab therapy. See paragraph 0005. In addition, DE GOEIJ teaches that a therapeutic agent for use in combination with the HER2 antibody may be an anti-cancer cytokine such as IFNγ. See paragraph 0445.
Thus, DE GOEIJ’s disclosure of pertuzumab, trastuzumab, and IFNγ in combination for the treatment of cancer renders claims 1 and 10 obvious. It would have been obvious to a person of ordinary skill in the art, at the effective filing date of the present invention to have modified the teachings of DE GOEIJ to disclose a method of treating a p185her2/neu-associated tumor in a subject comprising administering to the subject a therapeutically effective amount of a first anti-p185her2/neu antibody a second anti- p185her2/neu antibody, and interferon-gamma (IFNy) as recited in the present claims. One or ordinary skill in the art would have been motivated to use the recited combination of agents in the treatment of a p185her2/neu-associated tumor because DE GOEIJ teaches that pertuzumab, trastuzumab, and IFNγ are known to be useful for the treatment of HER2-related cancers. Thus, although the claimed combination is not explicitly set forth in DE GOEIJ, it is clear that DE GOEIJ teaches that these agents may be combined in a composition specifically for treating p185her2/neu-associated tumor, rendering the method of claims 1, 3 – 5, 10, and 12 - 14 obvious.
Regarding claim 2, DE GOEIJ teaches that trastuzumab binds to domain IV of the HER2 ectodomain and pertuzumab binds to domain II of the HER2 ectodomain, i.e. different epitopes of the ectodomain of HER2. See paragraphs 0004-0005. Additionally, DE GOEIJ teaches that the HER2 antibodies of the invention bind to novel epitopes of the extracellular domain. See paragraph 0011, Example 28 and Table 16.
Regarding claims 6 – 8 and 15 – 17, DE GOEIJ’s method comprises the administration of a therapeutically effective amount of a HER2 antibody and at least one additional therapeutic agent to a subject in need thereof, and DE GOEIJ teaches that the additional therapeutic agent may be selected from an anti-mitotic agent, such as taxanes, for instance docetaxel and paclitaxel. See paragraphs 0435 and 0438.
Regarding claims 9 and 18, DE GOEIJ teaches the treatment of breast cancer. See paragraph 0458.
Regarding claim 10, DE GOEIJ teaches that the HER2 antibody may also be administered prophylactically in order to reduce the risk of developing cancer. See paragraph 0431.
Regarding claim 19, DE GOEIJ’s method reduces the risk of recurrence when a cancer is in remission. See paragraph 0431.
Regarding claim 20, DE GOEIJ’s method delays tumor growth over 30 days. See Fig. 18A, day 63, which is 35 days after treatment starting at day 28.
Response to Arguments
On p. 5, last paragraph – p. 6, fourth paragraph, of the reply of 09/18/2025, Applicant argues that “[t]he Office has not established a prima facie case of obviousness with respect to claims 1 and 10 because the Office has not articulated a rational underpinning for why a person of ordinary skill in the art, reviewing De Goeij, would have chosen to combine two anti-pl85her2/neu antibodies or antigen binding portions thereof, with IFNγ to arrive at the combination used in the claimed method. . . . In fact, one of ordinary skill in the art might be led away from adding a third ingredient given that the combination of pertuzumab and trastuzumab is already disclosed as having enhanced anti-tumor effects. Furthermore, there is only generic disclosure in De Goeij regarding combinatorial approaches to cancer treatment. For instance, there is a passing mention of IFNy in a list of various cytokines . . .”
Applicant’s arguments have been considered but not found persuasive because DE GOEIJI teaches that “[t]he complementary mechanisms of action of pertuzumab and trastuzumab reportedly results in enhanced anti-tumor effects and efficacy when combined in patients who progressed during prior trastuzumab therapy” (see paragraph 0005) and that “[t]herapeutic agents that may be administered in combination with a HER2 antibody of the present invention as described elsewhere herein, such as, e.g., anti-cancer cytokines” (see paragraph 0356). Although IFNy is provided in a list of cytokines that may be used in combination with the HER2 antibodies, the list is not especially large and the claimed combination may be arrive at with routine experimentation. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05(II)(A).
Furthermore, MPEP 2143.01 (I) states that “[t]he disclosure of desirable alternatives does not necessarily negate a suggestion for modifying the prior art to arrive at the claimed invention. In In re Fulton, 391 F.3d 1195, 73 USPQ2d 1141 (Fed. Cir. 2004), . . . [t]he court stated that ‘the prior art’s mere disclosure of more than one alternative does not constitute a teaching away from any of these alternatives because such disclosure does not criticize, discredit, or otherwise discourage the solution claimed….’ Id. . . . thus providing a motivation to combine, which need not be supported by a finding that the prior art suggested that the combination claimed by the applicant was the preferred, or most desirable combination over the other alternatives. Id. See also In re Urbanski, 809 F.3d 1237, 1244, 117 USPQ2d 1499, 1504 (Fed. Cir. 2016).”
On p. 6, second to last paragraph – p. 7, third paragraph, Applicant argues that the “rejection would still fall with Applicant's showing of unexpected results for the claimed method. For instance, FIG. 47 demonstrates the remarkable tumor-free survival of MM TVneu mice that were administered the combination used in the claimed method”.
Applicant’s argument has been fully considered but not found persuasive because the conditions of FIG. 47 is limited to a very specific dosage and regimen in mice and is thus not commensurate in scope with the claims.
The invention as a whole is clearly prima facie obvious to one of ordinary skill in the art at the time the invention was made. In particular, the claimed invention is the result of combining prior art elements according to known methods to yield predictable results.
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.
Previous rejection, withdrawn: claims 1 – 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1 of U.S. Patent No. 11,446,516 (IDS) in view of DE GOEIJ.
On p. 7 of the reply of 09/18/2025, “Applicant notes that the present application is a divisional application of U.S. Application No. 17/375,459, which issued as U.S. Patent No. 11,446,516, the cited reference. During prosecution of U.S. Application No. 17/375,459, the Office restricted out and withdrew claims 13- 33, which were directed to methods of treating a pl85her2/neu-associated tumor in a subject, or prophylactically treating a subject who is predisposed to developing a pl85her2/neu-associated tumor. See Final Office Action dated March 1, 2022 in U.S. Application No. 17/375,459.”
Thus, during the prosecution of U.S. Application No. 17/375,459 (issued as U.S. Patent No. 11,446,516), a restriction among groups of three methods was required. Because the claimed method was a non-elected group in the restriction requirement, this rejection is withdrawn.
Conclusion
Claims 1 – 20 are rejected.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ESTELLA M. GUSTILO whose telephone number is (703)756-1706. The examiner can normally be reached Monday - Friday 9:00 AM - 5:00 PM.
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/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/PETER J REDDIG/Primary Examiner, Art Unit 1646
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