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 .
Claim Status
No new claim amendments have been submitted. Thus, as noted in the previous Office Action (03/11/2026) for the claims submitted 12/08/2023, claims 8-9 are pending in the instant application.
Claims 8-9 are under examination in the instant office action.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/11/2026 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Double Patenting - Withdrawn
Claims 8-9 were rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-5, 7, 9, 11-15, and 20-21 of U.S. Patent No. 12,485,299 (herein after referred to as "second reference patent").
On Pages 3-5 of Remarks (06/11/2026), Applicant argues that the Examiner specifically relies upon a structure provided in claim 12 of the second reference patent, however the structure identified and relied upon was inadvertently retained in issued claim 12 as a result of a USPTO error. During prosecution of the second reference application, the recited structure relied upon by the Examiner was expressly deleted from then-pending claim 49 in the amendment filed 10/14/2023, and as such the claim does not accurately reflect the amendment entered during prosecution. Applicant submitted a request for a Certificate of Correction to remove the erroneously retained structure relied upon by the Examiner. It is noted that the request for a Certificate of Correction regarding the second reference patent has been submitted and subsequently approved on 07/01/2026. In view of the correction to remove the relied-upon structure, the rejection of claims 8-9 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 4-5, 7, 9, 11-15, and 20-21 of U.S. Patent No. is withdrawn.
Double Patenting - Maintained
Claims 8-9 stand as rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 8-10, 13, and 23 of U.S. Patent No. 11,717,576 (herein after referred to as “first reference patent”) in view of WO 2015/165413 A1 (US equivalent US 2017/0112944 A1 relied upon for translation; herein after referred to as “Qin”).
With regard to the above-listed claim rejection, Applicant argues the following on Pages 2-3 of Remarks (06/11/2026):
The pending claims of the present application and the claims of the '576 patent are patentably distinct. The '576 patent claims ADC intermediates comprising a linker-payload construct. The claims of the '576 patent do not claim an antibody-drug conjugate or recite an antibody component. In contrast, the pending claims are directed to specific antibody-drug conjugates ("ADCs") in which the linker-payload moiety is conjugated to a specific antibody. Although the linker recited in the pending claims may be the same as the linker present in the claimed intermediates of the '576 patent, the claimed subject matter as a whole is structurally distinct. The antibody is not merely an additional substituent. Rather, it is a substantial and essential component of the claimed invention. Conjugation of the linker-payload intermediate to an antibody creates a different chemical entity having a distinct structure, identity, and utility from the intermediate itself.
The Examiner fails to provide any articulated reason or motivation to select and combine the specific components (i.e., an antibody comprising instant SEQ ID NOs: 1 and 2) from the vast array of possibilities available in the art. The '576 patent claims a broad class of linker-payload intermediates but provides no teaching or direction pointing toward an antibody comprising SEQ ID NOs: 1 and 2. On the other hand, the linker disclosed in Qin is different from the particular linker-payload of the '576 patent. There would be no motivation to combine the specific antibody with the particular linker-payload of the '576 patent. The Examiner's argument relies entirely on the disclosure of the present application, which constitutes impermissible hindsight.
The specification demonstrates that the claimed ADC exhibits advantageous and unexpected biological activity. In Effect Example 1, the activity of HER2 targeted immunoconjugates was evaluated in vitro. The results showed that AC102-6-l-l (the claimed ADC) induced higher TNFa production than the antibody Ab000l, and the effective concentration of AC102-6-l-l was much lower than the payload Resiquimod. Notably, another immunoconjugate AC102-5-l-l showed no obviously different activity compared to Ab000l. The activity of HER2 targeted immunoconjugates was also evaluated in vivo (Effect Example 2). In vivo results showed that while the antibody itself, Ab000l, showed very limited anti-tumor activity, AC102-5-l-l and AC102-6-l-l almost cured the tumors at the end (FIG. 7). These results demonstrate that the claimed ADC possesses advantageous biological properties. These beneficial effects are not taught by the '576 patent claims or the Qin reference. Therefore, the claimed ADCs are not obvious ADCs that can be obtained from ADC intermediates claimed in the '576 patent.
Applicant’s arguments have been fully considered, but are deemed not persuasive.
Specifically with regard to the first two arguments above, the following are noted:
The disclosure of the first reference patent specifically indicates uses for the claimed intermediates; notably, Column 33 (Lines 40-46) and Column 40 (Lines 19-27) explicitly disclose the use of intermediates claimed by the first reference Application in the preparation of, for example, antibody-drug conjugates.
The Qin reference is solely relied upon to establish that it would have been within the level of one having ordinary skill in the art to conjugate an antibody, such as the HER2 antibody taught by Qin (comprising instant SEQ ID NOs: 1 and 2) to a drug-linker via an amine group to yield an antibody-drug conjugate using known and established methods in the art.
“Any judgement on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant’s disclosure, such a reconstruction is proper.” In re McLaughlin 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971).
A motivation and rationale was provided, wherein it would have been prima facie obvious to one of ordinary skill in the art that the compounds of the first reference patent could be conjugated to an antibody (e.g., an antibody comprising instant SEQ ID NOs: 1 and 2) via the terminal -NH2 group according to known methods with a reasonable expectation of success, as suggested by Qin. One of ordinary skill in the art would have been motivated to make such a modification because the resulting conjugate (i.e., ADC) would be expected to be useful as a targeted cancer therapeutic (i.e., specific to HER2-expressing cancers). Furthermore, the conjugation of an antibody, such as taught by Qin, to a single linker of the first reference application would correspond to a z of 1, which specifically reads on instant claims 8 and 9.
Specifically with regard to the arguments of unexpected results in the third argument, the following are noted:
MPEP 716.02b: The evidence relied upon should establish "that the differences in results are in fact unexpected and unobvious and of both statistical and practical significance." Ex parte Gelles, 22 USPQ2d 1318, 1319 (Bd. Pat. App. & Inter. 1992) (Mere conclusions in appellants’ brief that the claimed polymer had an unexpectedly increased impact strength "are not entitled to the weight of conclusions accompanying the evidence, either in the specification or in a declaration."); Ex parte C, 27 USPQ2d 1492 (Bd. Pat. App. & Inter. 1992) (Applicant alleged unexpected results with regard to the claimed soybean plant, however there was no basis for judging the practical significance of data with regard to maturity date, flowering date, flower color, or height of the plant.). See also In re Nolan, 553 F.2d 1261, 1267, 193 USPQ 641, 645 (CCPA 1977) and In re Eli Lilly, 902 F.2d 943, 14 USPQ2d 1741 (Fed. Cir. 1990) as discussed in MPEP § 716.02(c). The data being argued by Applicant does not provide any statistical analyses, and as such it is unclear if the results being argued are of both practical and statistical significance.
The data compares ADCs, corresponding to AC102-6-1-1 (an instantly claimed species) and AC102-5-1-1 (distinct linker structure not claimed), the unconjugated antibody thereof (Ab0001), and the unconjugated drug (i.e., Resiquimod). The comparison of AC102-6-1-1 to structurally distinct AC102-5-1-1 is not commensurate in scope with the claims, which are only drawn to AC102-6-1-1 and wherein the drug-linker of AC102-6-1-1 is explicitly claimed by the first reference patent. Additionally, one of ordinary skill in the art would expect that the ADCs -would perform better and have increased anti-tumor effects compared to the unconjugated drug and/or antibody because of the ADCs (i) enabling specific delivery of the drug to tumor cells and (ii) exerting multiple mechanisms of action via the antibody and the drug. Furthermore, all of the data argued is specifically drawn to the instantly claimed antibody, relative to any other anti-HER2 antibody, and as such the data presented does not support that it is the instantly claimed antibody that is specifically attributable to the therapeutic effects observed with the instantly claimed ADC species.
In view of the above, the rejection of claims 8-9 on the ground of nonstatutory double patenting as being unpatentable over claims 1-4, 6, 8-10, 13, and 23 of U.S. Patent No. 11,717,576 (herein after referred to as “first reference patent”) in view of Qin is maintained.
Conclusion
Claims 8-9 are pending. Claims 8-9 are rejected. No claims are allowed.
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 ALYSSA RAE STONEBRAKER whose telephone number is (571)270-0863. The examiner can normally be reached Monday-Thursday 7:00 am - 5:00 pm.
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/ALYSSA RAE STONEBRAKER/Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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