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 .
Response to Amendment
Applicant’s amendment filed 04/02/2026 is acknowledged. Claims 1-2 and 4-15 are amended, claims 16-21 are new, and claim 3 is cancelled. Claims 1-2 and 4-21 are under examination.
Objections Withdrawn
The objection to claim 15 for minor informalities is withdrawn in response to Applicant’s amendment correcting the grammatical errors in the claim.
Rejections Withdrawn
Any previous rejections of claim 3 are hereby withdrawn in response to Applicant’s cancelation of the claim. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 112
The rejections of claims 2, 6, and 9-15 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in response to Applicant’s amendment removing the indefinite language outlined at pages 2-3 of the Office action mailed 01/07/2026.
Claim Rejections - 35 USC § 101
The rejections of claims 1-2 and 4-15 under 35 U.S.C. 101 because the claimed invention is directed to a natural product without significantly more is withdrawn in response to Applicant’s amendment of the claims. The amended claims are drawn to a method of treating squamous cell carcinoma.
New Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION. —The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 12 is newly rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Applicants’ amendments to claim 12 in the response filed on 04/02/2026 removes “and y is 2, 3, or 4 days.” Due to this deletion, “y consecutive days” is now indefinite because the quantity for “y” is not further defined in the claim. While dependent claim 13 defines y as 2, 3, or 4 days, claim 12 does not; for the purposes of compact prosecution, y in claim 12 will be interpreted to be 2, 3, or 4 days.
Rejections Maintained
Claim Rejections - 35 USC § 102
The rejection of claims 1-2 and 4-11 under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Lewis et al., 2018 (WO2018134784A1) is maintained and claims 15-18 are newly rejected. Claim 12 is no longer included in this rejection.
This is a modified rejection necessitated by Applicants’ amendments to the claims in the response filed on 04/02/2026.
The amended instant claims are drawn to a method for treating squamous cell carcinoma comprising administering an IL-15/IL-15Ra complex to a patient that is resistant or refractory to at least one immune checkpoint inhibitor treatment, where the immune checkpoint inhibitor is a PD-1 antagonist and the squamous cell carcinoma is skin squamous cell carcinoma. The amended claims are drawn to treatment with or without the addition of a PD-1 antagonist. The amended claims are drawn to the administration being a cyclical administration regimen.
Lewis teaches an IL-15/IL-15Ra complex that can treat non-small cell lung cancer with squamous histology, head and neck squamous cell carcinoma (pg. 12-14), and squamous cell carcinomas including malignancies, e.g., in the lung, esophagus, skin, head and neck region, oral cavity, anus, and cervix (pg. 50-51) with or without being administered in combination with a PD-1 antagonist (claims; pg. 14-15) that the patient is resistant or refractory to (pg. 3-5). Lewis teaches that this treatment results in at least a 30% size reduction in the tumor and that it is mediated by the NK cells of the innate immune response (pg. 31 & 50). Therefore, Lewis anticipates amended instant claims 1-2, 4-11, and 15-18.
Response to Arguments
Applicant argues at page 7 that Lewis provides various generalized lists of various cancers, does not provide more than the general knowledge that such cancer indications exist and potentially could be treated, does not provide any data supporting that the claimed complexes show an effect in the treatment of squamous cell carcinoma in a patient that is resistant or refractory to checkpoint inhibitor treatment, only describes in vitro examples and hypothetical examples, doesn’t demonstrate efficacy, and does not relate to treating skin squamous cell carcinoma.
This has been fully considered, but is not found to be persuasive. Lewis explicitly teaches a method that can treat squamous cell carcinomas, including skin squamous cell carcinoma (pg. 12-14 & 20-51). No where does Lewis say that skin squamous cell carcinoma “potentially could be treated,” as Applicant asserts. Furthermore, the Examples viewed in isolation are not where Lewis teaches a method to treat squamous cell carcinoma, including skin squamous cell carcinoma; Lewis teaches in sections titled “Uses of the Combination Therapies” and “Dose regimens for prophylactic and therapeutic uses” effective embodiments of a method to treat squamous cell carcinoma, including skin squamous cell carcinoma. In the Examples, Lewis uses an in vitro model to demonstrate the mechanism through which the IL-15/IL-15Ra complex functions and describes in detail how to use their invention. It is this demonstration of a mechanism of action, detailed descriptions of how to use the method, and explicit teachings that embodiments include squamous cell carcinomas, including skin squamous cell carcinoma, which collectively teaches the claimed invention. As such, Lewis’s disclosure is indicative of the efficacy of treating skin squamous cell carcinoma based on this demonstration of the IL-15/IL-15Ra complex’s mechanism of action, which reads onto the instant claims.
Claim Rejections - 35 USC § 103
The rejection of claims 1-2 and 4-15 under 35 U.S.C. 103 as being obvious over Lewis et al., 2018 (WO 2018134784 A1) in view of Morisseau et al., 2012 (WO2012175222-A1) is maintained and 16-21 are newly rejected. This is a modified rejection necessitated by Applicants’ amendments to the claims in the response filed on 04/02/2026.
Amended claims 1-2, 4-11, and 15-18 are recited above. Amended claim 12 is drawn to the IL-15/IL-15Ra complex administered according to a cyclical regimen, comprises:(a) a first period of x days during which the IL-15/IL-15Ra complex is administered at a daily dose on y consecutive days at the beginning of the first period followed by x-y days without administration of the IL-15/IL-15Ra complex, wherein x is 5-21 days; (b) repeating the first period at least once; and (c) a second period of z days without administration of the IL-15/IL-15Ra complex, wherein z is 5-70 days. Amended claim 13 is drawn to the cyclical administration regimen of claim 12, wherein x is 7 days, y is 2, 3 or 4 days and z is 7 or 14 days. The amended claims are drawn to the daily dose of the IL-15/IL-15Ra complex is 0.1 ug/kg to 50 ug/kg or 0.6 ug/kg to 12 ug/kg. The amended claims are drawn to an IL-15/IL-15Ra complex where the human IL-15Ra sushi domain comprises the sequence of SEQ ID NO: 6, the human IL-15 comprises the sequence of SEQ ID NO: 4, and the IL- 15/IL-15Ra complex as a whole is the sequence of SEQ ID NO: 9.
The teachings of Lewis are recited above. Further, Lewis teaches dosing cycle in the regimen comprises: (a) subcutaneously administering a dose of the IL- 15/IL-15Ra complex to the subject at set time intervals over a first period of time; and (b) no administration of the IL-15/IL-15Ra complex for a second period of time (page 7). Lewis teaches IL-15/IL-15Ra complex being at a frequency of every 7 days (page 7). Lewis teaches the first period being 3 weeks long and the second period being 1 week long (page 7). Lewis teaches the first period lasts is 7 days. Lewis teaches the second period is 7 or 14 days (page 7). Therefore, Lewis teaches x being 7 days, y being 1 day, and z being 7 days. Lewis teaches a dose of the IL-15/IL-15Rα complex which is 0.1 μg/kg to 10 μg/kg (page 7).
Lewis does not explicitly teach the specific sequences for the complex. Lewis does not explicitly teach the cyclical administration regimen of claim 12, wherein y is 2, 3 or 4 days. Lewis does not explicitly teach the daily dose of the IL-15/IL-15Ra complex is 0.1 ug/kg to 50 ug/kg or 0.6 ug/kg to 12 ug/kg.
Morisseau teaches the IL- 15/IL-15Ra complex (SEQ ID NO: 17) with an identical sequence to instant SEQ ID NO: 9, which encompasses SEQ ID NO: 4 and 6. The alignment data between Morisseau SEQ ID NO: 17 and instant SEQ ID NO: 9 is shown below. SEQ ID NO: 4 has an identical alignment spanning from position 3 to position 63 in the diagram below. SEQ ID NO: 6 has identical alignment spanning from position 98 to position 211 in the diagram below.
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It would have been prima facie obvious to arrive at the claimed invention from the disclosure of Lewis and Morisseau. A person having ordinary skill in the art would have been motivated to make and use the invention as claimed because a person of ordinary skill would have been motivated to use the sequence of Morisseau to synthesize the IL- 15/IL-15Ra complex as disclosed by Lewis. A person having ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosure of the prior art references. Therefore, claims 13-14 and 19-21 are obvious in view of the disclosures of Lewis and Morisseau.
The prior art only differs from the claimed invention with respect to the claimed daily dosages and the number of days in the administration regimen. The Court has stated that generally such differences amount to mere optimization and will not support patentability unless there is evidence indicating the claimed feature is critical. It would have been prima facie obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to arrive at the claimed invention because an ordinary artisan would have found it obvious to optimize the daily dosages and the number of days in the administration regimen through routine experimentation. An ordinary artisan would have been motivated to optimize the daily dosages and the number of days in the administration regimen to make the most effective treatment. MPEP 2144 sets forth Applicant’s burden for rebuttal of a prima facie case of obviousness based upon routine optimization. Applicant must provide either a showing that the particular amount or range recited within the claims is critical; and/or a showing that the prior art reference teaches away from the claimed amount. In the instant case, the specification as filed provides no evidence that the particular amount or range recited within the claims is critical because the specification teaches effective embodiments of the claimed invention with x days ranging from 5-21, y days ranging from 2-4, z days ranging from 5-70 (page 27), and a daily dose of 0.1 ug/kg to 50 ug/kg (page 42), which is evidence of noncriticality to the claimed invention.
Response to Arguments
Applicant argues at page 8-9 that Morisseau provides no teaching, suggestion, or motivation regarding treating squamous cell carcinoma in a patient, wherein the patient is resistant to refractory to checkpoint inhibitor treatment and would therefore have no reason to modify the Lewis teaching.
This has been fully considered, but is not found to be persuasive. In response to applicant's arguments against the references individually, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). As outlined above, since Lewis teaches the complex can treat skin squamous cell carcinoma, an ordinary artisan would be motivated to look to the prior art to obtain sequences for synthesizing and using the complex. An ordinary artisan would find it obvious that the sequence taught by Morisseau would be useful in the method taught by Lewis to treat skin squamous cell carcinoma.
Double Patenting
The provisional rejection of claims 1-2 and 4-15 on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of co-pending Application No. 18/033,524 is maintained for reasons of record. In addition, new claims 16-21 are hereby included in this rejection.
The provisional rejection of claims 1-2 and 4-15 on the ground of nonstatutory double patenting as being unpatentable over claims 42-53 of co-pending Application No. 17/612,432 is maintained for reasons of record. In addition, new claims 16-21 are hereby included in this rejection.
Response to Arguments
Applicants’ request deferral of this issue at p.9 of the Remarks filed 04/02/2026 until other issues of patentability are resolved in their response filed 04/02/2026 is noted. However, deferral of arguments is not proper; an argument after the claims have been found otherwise allowable that double patenting does not exist will not be considered timely. Accordingly, the rejections on the ground of nonstatutory double patenting are maintained.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
No claims are allowed.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOSEPH CESARE whose telephone number is (571)272-6908. The examiner can normally be reached Monday - Friday 10am-4pm.
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/JOSEPH D. CESARE/ Examiner, Art Unit 1675
/JEFFREY STUCKER/ Supervisory Patent Examiner, Art Unit 1675
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