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 .
Response to Amendment
The Amendment filed May 5, 2026 in response to the Non-final rejection of February 5, 2026 is acknowledged and has been entered.
Claim 29 was cancelled. Claims 20-28, and 30-33 remain unchanged and are currently pending.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office Action.
Objections/Rejections Withdrawn
The objection to the disclosure (action mailed 02/05/2026, para 4) is withdrawn in view of applicant’s amendment.
The objection to Claim 29 under 37 CFR 1.75 as being a substantial duplicate of claim 30 is moot as applicants have cancelled claim 29.
Rejections Maintained
The rejection of claim(s) 20-23, 27-28, and 30-33 under 35 U.S.C. 103 as being unpatentable over US2018/0312604 (Throsby et al. Nov. 1, 2018) in view of Hendrikx et al. (The Oncologist, 22(10), 2017) is maintained for the reasons of record and for the reasons set forth below.
Applicants do not dispute the teachings of Throsby et al. as they relate to treating head and neck cancer with an antibody as currently claimed. The only dispute is whether or not the combination of Throsby et al. in view of Hendrikx et al. would have led one of ordinary skill in the art, before the filing date of the instantly claimed invention, to include administering a flat dose of 1500 mg of the bispecific antibody.
Applicants argue (Remarks, page 2) that Throsby “teaches away” from the use of any flat dose administration and instead relies on weight-based dosages. This argument has been considered but is not found persuasive because there is no clear “teaching away” here. The fact that Throsby et al. does not speak of alternative dosing regimens like flat dose administration does not indicate that flat dosage administration is any less efficacious than weight-based dosages. Applicants are implying that one of ordinary skill in the art would NOT consider flat based dosing merely because it was not mentioned by Throsby. However, the failure to disclose another route of administration does not discredit nor otherwise discourage its use; especially when one considers that the other reference- Hendrikx et al. acknowledged applicant’s point- that most monoclonal antibodies in oncology relied upon weight-based dosages.
Applicants further argue that the weight-based dosage taught by Throsby teaches away from administering dosages as high as currently claimed (1500 mg). Applicant’s note that Example 8 of Throsby et al. describes a body weight-based dosing regimen wherein "a dose level of 25 mg/kg was selected for PB10651 as the highest dose in the present study,". Thus, applicants argue, a skilled person might consider estimating a human dose from animal studies by consulting the FDA guidelines "Estimating the Maximum Safe Starting Dose in Initial Clinical Trials for Therapeutics in Adult Healthy Volunteers." (Remarks, page 8, and Exhibit A) wherein Table 1 of the FDA guidelines indicates that the human equivalent dosage can be determined from cynomolgus monkeys by multiplying the animal dose by 0.32 (i.e., 25 mg/kg from Throsby results in 8 mg/kg for a human). Applicants argue that a human of 60 kg would result in a starting dose of 480 mg which is more than 3x less than the claimed amount. This argument has been considered and is a valid point if one of ordinary skill in the art were only set on trying one starting dose. But it ignores the advantages of fixed dosing as taught by Hendrikx et al. and assumes that only one dose would be given per week. For example, Table 1 in Hendrix et al. indicate that many of the approved doses of antibodies with a starting dose of around 5-10 mg/kg are given twice per week. Moreover, such an argument assumes that trial and error would not be attempted in practice, and as set forth previously, 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).
As set forth previously, Hendrikx et al., argues that fixed dosing of monoclonal antibodies has several advantages including efficiency of compounding, reduced drug spillage, fewer medication errors, and decreased costs (e.g., Introduction, page 1213; page 1219). Summarizing the results of in silico studies, Hendrikx notes that when minimal effects of body weight are observed on the volume of distribution and clearance of an antibody in plasma, fixed dose administration reduces interpatient variability compared to body weight-based dosing (pages 1215-1216). Even when strong effects of body weight are observed, Hendrikx argues that fixed dosing can still be considered for monoclonal antibodies with a wide therapeutic range for practical reasons (page 1217; Table 1).
Applicants further argue (Remarks, page 8) that while Hendrikx does discuss the benefits of fixed dosing, a skilled artisan would not have arrived at the claimed method from the combination of Hendrikx and Throsby with a reasonable expectation of success because the Office relies on the teaching that other antibodies, including panitumumab - - an anti-EGFR antibody, is amenable to a fixed dose regimen. Therefore, according to the Office, there would have been a reasonable expectation of success because Throsby teaches that PB10651 is widely tolerated at a wide range of body weight-based dosages. Applicants argue that the Office makes the same types of assumptions that the courts have warned against in the medical arts. Applicants refer to the decision in Eisai Co. V. Dr. Reddy's Laboratories, Ltd. (533 F.3d 1353, 1359 (Fed. Cir. 2008)), where the court observed that in the medical arts "potential solutions are less likely to be genuinely predictable," as compared with other arts such as the mechanical devises. Applicants argue that these further underscores the need for specific direction to be shown in the prior art and that that merely substituting one antibody for another is the type of unpredictability the court guards against.
This argument has been considered but is not found persuasive because the decision in Eisai Co. V. Dr. Reddy's Laboratories, Ltd. was not based on one of ordinary skill in the art arriving at an optimum dosage or using a different dosing regimen such as fixed dosing or weight-based dosing; rather the decision was based on the improper usage of lansoprazole as a lead compound. The courts found that converting lansoprazole to rabeprazole was not obvious because it was already highly lipophilic. Here, the MPEP states that Office personnel should recognize that a proper obviousness rejection of a claimed compound that is useful as a drug might be made beginning with an inactive compound, if, for example, the reasons for modifying a prior art compound to arrive at the claimed compound have nothing to do with pharmaceutical activity (MPEP 2143, Example 9). In contrast, the nexus between Hendrikx and Throsby was the use of antibodies for treating cancers in concert with the advantages of fixed dosing versus weight-based dosing as taught by Hendrikx et al. Further, as set forth previously, optimal drug dosages are an art-recognized result-effective variable that is routinely determined and optimized in the pharmaceutical art, and it is conventional and within the skill of those in the art to identify the optimal dosages and treatment intervals necessary to achieve desired working concentrations and therapeutic efficacy. Thus, Applicant’s arguments have been considered but have not been found persuasive and the rejection is maintained.
The rejection of Claim(s) 24-26 under 35 U.S.C. 103 as being unpatentable over US2018/0312604 (Throsby et al. Nov. 1, 2018) in view of Hendrikx (The Oncologist, 22(10), 2017) in further view of NIH, NCI’s Head and Neck Cancers Website (Wayback Machine, at least 2015) is maintained for the reasons of record and for the reasons set forth above as applicants have combined their arguments against obviousness by arguing against the combined teachings of Throsby and Hendrikx (Remarks, pages 7-9).
The rejection of claims 20-28, and 30-33 under the ground of nonstatutory double patenting as being unpatentable over claims 1-2, and 6-30 of U.S. Patent No. 11939394 in view of Hendrikx (The Oncologist, 22(10), 2017) is maintained for the reasons of record as applicants only generally point to their previous deficiencies of Hendrikx.
The rejection of Claims 20-28, and 30-33 as provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 31, 34, 37-41, 43-44, and 47 of copending Application No. 17921042 (reference application) is maintained for the reasons of record. Applicant asserts that this rejection is a provisional rejection and since Applicant believes each of the rejections has been overcome, the current application should be allowed to pass to grant according to M.P.E.P.804(B)(1)(b)(i). This argument has been considered but is not found persuasive because applicant’s arguments under 35 USC 103 were not found persuasive.
The rejection of Claims 20-28, and 30-33 as provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 30, 33-34, 40-42, 44, 48, 49-53 of copending Application No. 17632181 (reference application) in view of Hendrikx (The Oncologist, 22(10), 2017) and Cesare et al. (Clin.Can.Res., Vol 20(4), 2014) is maintained for the reasons of record.
Applicants argue (Remarks, page 5) that the claims of the '181 application are directed to a method of treating cancer with a combination of a bispecific antibody that binds EGFR and LGR5 and a topoisomerase I inhibitor and that there is nothing in claims 30-32, 35, and 42-44 of the '181 application that teaches or suggests any dosage of the claimed bispecific antibody, much less a flat dose of 1500 mg. This argument has been considered but is not found persuasive because it does not consider the teachings of Hendrikx which the body of the rejection included. The fact that Hendrikx reference was not placed in the heading of the rejection was a typographical oversight. Thus, the rejection is maintained for the reasons of record and for the reasons set forth above regarding the decision in Eisai.
The rejection of Claims 20-28, and 30-33 as provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 42-65 of copending Application No. 18/268168 (reference application) in view of Hendrikx (The Oncologist, 22(10), 2017) and US2018/0312604 (Throsby et al. Nov. 1, 2018) is maintained. The fact that Hendrikx reference was not placed in the heading of the rejection was a typographical oversight as the teachings of Hendrikx were addressed. Applicant asserts that this rejection is a provisional rejection and since Applicant believes each of the rejections has been overcome, the current application should be allowed to pass to grant according to M.P.E.P.804(B)(1)(b)(i). This argument has been considered but is not found persuasive because applicant’s arguments under 35 USC 103 were not found persuasive.
The rejection of Claims 20-28, and 30-33 as provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 29-59 of copending Application No. 18431642 (reference application) in view of Hendrikx (The Oncologist, 22(10), 2017) is maintained. Applicant asserts that this rejection is a provisional rejection and since Applicant believes each of the rejections has been overcome, the current application should be allowed to pass to grant according to M.P.E.P.804(B)(1)(b)(i). This argument has been considered but is not found persuasive because applicant’s arguments under 35 USC 103 were not found persuasive. The fact that Hendrikx reference was not placed in the heading of the rejection was a typographical oversight.
The rejection of Claims 20-28, and 30-33 as provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 3, 9-13, 16, 18, 20, 23, 27, 36-42 of copending Application No. 18694252 (reference application) is maintained. Applicant asserts that this rejection is a provisional rejection and since Applicant believes each of the rejections has been overcome, the current application should be allowed to pass to grant according to M.P.E.P.804(B)(1)(b)(i). This argument has been considered but is not found persuasive because applicant’s arguments under 35 USC 103 were not found persuasive.
No claim is allowed.
Conclusion
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.
11939394
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/GARY B NICKOL/Primary Examiner, Art Unit 1643
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