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. Claims 1 and 10 have been amended. Claims 1 – 20 are currently pending and are the subject of this Office Action.
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 08/20/2026 has been entered.
REJECTION WITHDRAWN
Claim Rejections - 35 USC § 103
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).
In view of the claim amendments in the reply of 08/20/2026, this rejection is withdrawn.
NEW REJECTION, NECESSITATED BY CLAIM AMENDMENTS
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.
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) in view of JAIME-RAMIREZ (Jaime-Ramirez, AC, et al. IL-12 Enhances the Antitumor Actions of Trastuzumab via NK Cell IFN-γ Production, The Journal of Immunology, Volume 186, Issue 6, March 2011, Pages 3401–3409; see PTO-892: Notice of References Cited submitted with this Office Action) and CARSON (Carson, W. Interleukin-12, Paclitaxel, and Trastuzumab in Treating Patients With Solid Tumors. ClinicalTrials.gov identifier: NCT00028535. Updated 06/04/2013. Accessed 09/14/2026. clinicaltrials.gov/study/NCT00028535; see PTO-892).
Present independent claim 1 is directed to a method of treating a p185her2/neu-associated tumor in a subject, comprising: (i) administering to the subject a therapeutically effective amount of a first anti-p185her2/neu antibody or an antigen binding portion thereof, and a second anti-p185her2/neu antibody or an antigen binding portion thereof, and (ii) administering to the subject an effective amount of interferon-gamma (IFNγ); wherein at least one of the first anti-p185her2/neu antibody or the antigen binding portion thereof and the second anti-p185her2/neu antibody or the antigen-binding portion thereof is administered to the subject 1-5 days before the administration of the 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. See paragraph 0005. DE GOEIJ further 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.
Although DE GOEIJ teaches parts (i) and (ii) of the method of present claim 1, DE GOEIJ does not expressly teach that the antibodies are administered to the subject 1-5 days before the administration of the IFNγ.
JAIME-RAMIREZ is directed to the discovery that tumor regression in response to trastuzumab (humanized of murine anti-HER2/neu mAb 4D5) plus IL-12 is mediated through NK cell IFN-γ production and provides a rationale for the coadministration of NK cell-activating cytokines with therapeutic mAbs. See JAIME-RAMIREZ at the abstract.
CARSON is directed to a clinical trial of the combination therapy of interleukin-12, paclitaxel, and trastuzumab. See CARSON at Study Overview: Brief Summary. CARSON teaches that patients receive trastuzumab (Herceptin®) IV over 30-90 minutes on days 1, 8, and 15 and paclitaxel IV over 3 hours on day 1 of course 1 and that beginning with course 2, patients receive trastuzumab and paclitaxel as in course 1 and interleukin-12 subcutaneously on days 2, 5, 9, 12, 16, and 19. Thus, CARSON teaches the administration of anti-HER2/neu mAb trastuzumab one course prior to the cytokine IL-12, which according to JAIME-RAMIREZ exhibits similar anti-tumor mechanism as the cytokine IFNγ. Then in course 2, trastuzumab is administered at least one day prior to IL-2. Thus, because JAIME-RAMIREZ teaches that IFN-γ is required for the antitumor actions of trastuzumab and that IFN-γ is induced by IL-12 (see JAIME-RAMIREZ at p. 3408, right column, second paragraph), it would have been obvious to one having ordinary skill in the art to replace IL-12 in CARSON’s method with IFN-γ.
It would have been prima facie obvious to the person of ordinary skill in the art, at the effective filing date of the claimed invention, to arrive at the claimed invention from the disclosures of DE GOEIJ, JAIME-RAMIREZ, and CARSON. The artisan would have been motivated to conceive and use the method of claim 1 because DE GOEIJ teaches that complementary mechanisms of action of the anti-p185her2/neu antibodies pertuzumab and trastuzumab results in enhanced anti-tumor effects and efficacy when combined (see DE GOEIJ at paragraph 0005) and further teaches that a therapeutic agent for use in combination with the HER2 antibody for treating cancer may be the anti-cancer cytokine IFNγ (see DE GOEIJ at paragraph 0446); JAIME-RAMIREZ teaches that IFN-γ is required for the antitumor actions of anti-HER2/neu antibody trastuzumab which is be enhanced by IL-12, and CARSON teaches that IL-12 is administered 1 – 5 days after the administration of the trastuzumab. The artisan would have a reasonable expectation of success from the combined teachings of the cited references.
Thus, the cited references render the method of claims 1 – 5, 10 and 12 – 14 obvious.
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 11, because DE GOEIJ teaches the treatment combination that includes trastuzumab and pertuzumab (which bind distinct epitopes of HER2), DE GOEIJ also teaches the limitations of claim 11.
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, first paragraph of the reply of 08/20/2026, Applicant argues that it was discovered that treatment of the tumors with anti-erbB2/neu mAb initially
for at least 24 hours prior to IFN-y or concomitant with IFN-γ led to dramatic inhibition of tumor growth in vivo.
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” (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).
JAIME-RAMIREZ teaches that “[t]he combination of IL-12 and an anti-HER2/neu mAb [4D5] mediated superior antitumor activity compared with that of either agent alone. The mechanism of action appeared to require the actions of NK cells and IFN-γ.” See JAIME-RAMIREZ at p. 1308, right column, second paragraph and at FIGURE 3, p. 3403, and below:
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Thus, JAIME-RAMIREZ renders the effect of anti-erbB2/neu mAb (anti-HER2/neu) concomitant with IFN-γ leading to inhibition of tumor growth in vivo obvious.
CARSON expected the significance of administering trastuzumab prior to the cytokine by teaching a regimen that included administering trastuzumab 1 day prior to the cytokine in course 2 (see discussion above).
On p. 6, third paragraph of the reply of 08/20/2026, Applicant argues that first disabling the erbB2 kinase with mAb followed by IFN-y or prolonged co-treatment with mAb and IFN-γ treatment produced the most significant viability effect on breast tumor cells.
Applicant’s argument has been considered but is found not persuasive because CARSON teaches the administration of a first course of trastuzumab then a second course with trastuzumab and paclitaxel as in course 1 and interleukin-12 subcutaneously on days 2, 5, 9, 12, 16, and 19. See CARSON at Detailed Description: OBJECTIVES. Because JAIME-RAMIREZ teaches that IL-12 and IFN-γ lead to superior antitumor activity as discussed above, it would have been obvious that CARSON’s method with IFN-γ instead of IL-12 would also lead to the same observation as that of the Applicant.
Conclusion
Claims 1 – 20 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Estella Gustilo whose telephone number is (703)756-1706. The examiner can normally be reached Monday - Friday 9:30 AM - 5:30 PM.
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/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
