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
Applicant's response filed 08-13-2026 to the non-final rejection mailed 05-13-2026 has been received and entered. election with traverse of Group I in the reply filed on 03-26-26 is acknowledged. Claims 61-62 were cancelled. Claims 2-4, 30, 34, 41-42, 49, 59, and 60 were amended.
Claims 2-4, 9-10, 14, 16-23, 30-31, 34-35, 39, 41-42, 47-49, and 59-60 are pending and under consideration.
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Objections Withdrawn
Previous objections of Claims 3 and 62 are withdrawn in view of applicants’ amendments and cancellation of claim 62.
Rejections Withdrawn
The rejection of claims 3-4, 41-42, and 62, under 112(b) for reciting the phrase "in particular" or “more in particular” is withdrawn in view of applicants’ amendments and cancellation of claim 62.
The rejection of Claims 30 and 49 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in view of applicants’ amendments.
The rejection of Claim(s) 61-62 under 35 U.S.C. 102(a)(1) as being anticipated by WO2018056821 (Geuijen et al., published 03/2018, applicant’s IDS) is withdrawn in view of the cancellation of said claims.
Rejections Maintained
The rejection of Claims 2 and 35 under 35 USC 112(b) as indefinite for requiring CDR sequences (CDR1, CDR2, CDR3) without specifying the particular sequences associated with each CDR or the method by which they are meant to be determined (e.g. Chothia, Kabat, IGMT, etc.) is maintained for the reasons of record. Applicants’ amendment to further specify the clamed “heavy chain variable regions” does not address the indefiniteness of the rejection. The specification appears to teach that the CDRs are determined by Kabat numbering. An amendment stating such would obviate this rejection. Alternatively, applicant could remove the terms “CDR1, CDR2, and CDR3” and claim each heavy chain variable region by SEQ ID NO. Claims 3-4, 9-10, 14, 16-23, 30-31, 34, and 59-60 also remain rejected as all depend from claim 2 in the absence of defining the CDRs of Claim 2.
The rejection of Claim(s) 2-4, 9-10, 14, 16-23, 30-31, 34, 39, 41-42, 47-49, and 59-60 under 35 U.S.C. 103 as being unpatentable over WO2018056821 (Geuijen et al., published 03/2018, applicant’s IDS) in view of the teachings of Altintas et al. (WO 2019/025545, February 2019, IDS) is maintained for the reasons of record and for the reasons set forth below.
Applicants argue (Remarks, page 12) that Geuijen does not disclose administering the claimed multispecific antibody in a dose of between 10-50 mg, does not disclose administration once every week, once every two weeks, or once every three weeks, and does not disclose intravenous administration. Instead, the rejection relies on Altintas' disclosure of broad weight-based dosage ranges and generalized dosing guidance and concludes that the claimed dosing regimen would have been reached through routine optimization. Applicant respectfully submits that the rejection does not establish that a POSA would have been motivated to select the claimed fixed-dose regimen for the specifically claimed antibody species, does not establish a reasonable expectation of success in doing so, and does not establish that routine optimization would have led a POSA to the specific claimed flat-dose range of 10-50 mg for the specifically claimed multispecific antibodies. Applicants further argue that the Office does not identify any disclosure in Altintas establishing that the antibodies disclosed in Altintas are the same as the specifically claimed multispecific antibodies. Nor does the Office identify evidence establishing that the dosing information disclosed in Altintas for different antibodies would be expected to apply to the claimed multispecific antibodies. This distinction is material. The claimed method is not directed to administering any CD137xPD-L1 bispecific antibody at any dose. It requires administering the claimed multispecific antibody at a specific fixed dose of between 10-50 mg and according to the claimed dosing schedule. The rejection therefore must establish why a POSA would have been motivated to administer the specifically claimed antibody species within the claimed 10-50 mg dose range and would have had a reasonable expectation of success in doing so. This argument has been considered but is not found persuasive. The previous rejection stated that (like Geuijen) Altintas et al. also teaches methods of treating cancer with bispecific or multispecific antibodies that bind to the same antigens as currently claimed: bind to human PD-L1 and human CD137 (page 1, 1st paragraph). Thus, the references are reasonably similar to each other in that both relate to immunotherapy of cancer using similar antibodes. Further, Altintas et al. teach (page 82) that a physician or veterinarian having ordinary skill in the art may readily determine and prescribe the effective amount of the pharmaceutical composition required. For example, the physician or veterinarian could start doses of the binding agent (e.g. a bispecific antibody) employed in the pharmaceutical composition at levels lower than that required to achieve the desired therapeutic effect and gradually increase the dosage until the desired effect is achieved.
Applicants further argue (page 14) that Altintas' weight-based ranges encompass an enormous number of possible absolute doses. For example, for a 60 kg patient, the range of 0.001-10 mg/kg corresponds to approximately 0.06-600 mg, while the range of 0.1-50 mg/kg corresponds to approximately 6-3000mg. The claimed 10-50 mg fixed-dose range is only a narrow portion of those possible absolute amounts. Nothing identified by the Office directs a POSA to select that specific fixed-dose range from the many possible doses encompassed by Altintas. This argument has been considered but is not found persuasive as applicant’s flat dose range of 10-50 mg clearly falls into the possible ranges met by the prior art. Further, Altintas et al. does contemplate flat dosages. For example, Altintas et al teaches that the binding agent may be administered in a weekly dosage calculated as a fixed dose for up to 8 times, such as from 4 to 6 times when given once a week. Such regimen may be repeated one or more times as necessary, for example, after 6 months or 12 months. It is within the realm of routing experimentation in the field of pharmacology to test different dosages, routes of administration, and frequencies of administration. Finally, applicants have not provided a rationale demonstrating the criticality of the claimed 10-50 mg dosage range. The law is replete with cases in which the difference between the claimed invention and the prior art is some range or other variable within the claims. In such a situation, the applicant must show that the particular range is critical, generally by showing that the claimed range achieves unexpected results relative to the prior art range." In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). 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.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GARY B NICKOL, Ph.D. whose telephone number is (571)272-0835. The examiner can normally be reached M-F 9AM-5:30PM.
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/GARY B NICKOL/Primary Examiner, Art Unit 1643
