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
Claim listing filed October 20, 2025 is pending. Claims 2, 4-5, 10, 24-25, and 28-47 are canceled. Claims 23 and 27 are amended. Claims 1, 3, 6-9, and 11-22 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected species. Election was made without traverse in the reply filed on November 21, 2024. Claims 23 and 26-27 are examined upon their merits.
Information Disclosure Statement
The information disclosure statement filed on September 25, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Claim Objections
Applicant’s amendment to Claim 23 corrected the previous spelling error, and the claim objection of record is withdrawn.
The rejection of Claims 23 and 26-27 under 35 U.S.C. 102(a)(1) as being anticipated by Hoerr et al. US 2012/0213818 is withdrawn in view of Applicant’s amendments. Specifically, Hoerr does not teach wherein the IL2 is extended PK-IL2 as required by newly amended Claim 23.
Claim Rejections - 35 USC § 103 (New, necessitated by amendment)
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.
Claims 23 and 26-27 are rejected under 35 U.S.C. 103 as being unpatentable over Hoerr et al. US 2012/0213818 (of record) in view of Adabi et al. Iranian Biomedical Journal 2017.
The instant claims recite a medical preparation comprising: (a) a RNA encoding a polypeptide comprising IL2, wherein the IL2 is extended pharmacokinetic (PK)-IL2 (b) a RNA encoding a polypeptide comprising type I interferon, and (c) a RNA encoding a peptide or protein comprising an epitope for inducing a T-cell mediated immune response against a tumor-associated antigen (Claim 23). Dependent claims recite: wherein the medical preparation is a kit (Claim 26); wherein the RNA encoding a polypeptide comprising extended PK-IL2, the RNA encoding a polypeptide comprising type I interferon, and the RNA encoding a peptide or protein are in separate containers (Claim 27).
In regard to Claim 23, Hoerr teaches a method for immunostimulation comprising administration of (a) at least one mRNA that encodes at least one tumor antigen and (b) administration of at least one cytokine mRNA (paragraphs [0012] – [0014]). Hoerr teaches possible tumor antigens (paragraph [0034]) and possible cytokines including IL-2 and IFN-α (paragraph [0047]). Example 3 specifically uses IL-2 and IFN-α in separate experimental embodiments (paragraphs [0189] – [0192]). Hoerr teaches that it is preferable to combine (in a mixture or separately) two or more, preferably 2-4, cytokine mRNAs with one another in step (b) (paragraph [0031]) which anticipates the combination of RNA encoding IL-2, RNA encoding a type I interferon, and RNA encoding a tumor antigen in a medical preparation. Further, the preferred immune response to the mRNA is a Th1 immune response (paragraph [0033]) wherein Th1 is a subset of CD4+ T helper cells. The method taught by Hoerr utilizes a medical preparation that has applications in treating cancer (paragraph [0029]).
In regard to Claims 26-27, Hoerr teaches a kit that comprises the mRNA that encodes a tumor antigen and the mRNA that encodes a cytokine mRNA in separate containers so that the kit comprises at least two parts (paragraph [0110]). The kit will comprise more than two parts if the two or more cytokine mRNAs from step (b) are contained in the kit separately from one another (paragraph [0110]).
Hoerr fails to teach wherein the IL2 is an extended PK-IL2.
Adabi teaches that IL2 is an important factor in cancer immunotherapy, but one of the limitations of IL2 is its low serum half-life which requires repetitive high doses of IL2 to maintain effective concentrations that can cause unwanted side effect (abstract). Thus, different methods of extending IL2 half-life have been conducted such as binding IL2 to polyethylene glycol (PEG) chains and fusing IL2 to human serum albumin (HSA) (introduction paragraph 3). Adabi specifically investigates IL2 fused to an albumin-binding domain (ABD-rIL2) which improves IL2 half-life (increasing it from 46 minutes to 150 minutes) without reducing its bioactivity (abstract and results paragraph 5). The ABD-rIL2 was expressed recombinantly using a plasmid expression vector which encoded the ABD-rIL2 in E. coli Rosetta cells (abstract).
Based on these teachings, it would have been prima facie obvious to one of ordinary skill in the art, at the time the invention was made, to alter the mRNA encoding IL2 as taught by Hoerr to instead encode the extended PK-IL2 taught by Adabi. Adabi teaches that extended PK-IL2 are well understood in the art, and ABD-rIL2 specifically improves half-life without altering bioactivity. Because ABD-rIL2 was constructed using expression vectors (i.e. DNA to RNA to protein within a cell), it would be obvious to one of ordinary skill that mRNA encoding ABD-rIL2 could be constructed and used in the medical preparation of Hoerr with a reasonable expectation of success. The motivation to substitute RNA encoding IL2 for RNA encoding ABD-rIL2 is because ABD-rIL2 has a prolonged half-life which provides therapeutic benefits such as less frequent dosing and more stable drug concentrations.
Applicant's arguments filed October 10, 2025 have been fully considered but they are not persuasive. Applicant argues that Hoerr does not teach or suggest wherein the IL2 is extended PK-IL2. This deficiency is overcome in the 103 rejection above by the teachings of Adabi.
Applicant argues that in Hoerr paragraphs [0189]-[0192], IL2 and IFNα are not used in combination and they are used in protein form, not mRNA. Examiner agrees with Applicant’s interpretation of Hoerr paragraphs [0189]-[0192]. Examiner references these paragraphs to teach that out of all the cytokines Hoerr teaches, IL2 and IFNα were specifically evaluated in experimental examples (although separately and in protein form) which supports the selection of these two cytokines. Other cited sections of Hoerr make it clear that it is preferable to combine two or more cytokine mRNAs (of record). Applicant’s arguments are not persuasive.
Conclusion
No claim is allowed.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH COOPER PATTERSON whose telephone number is (703)756-1991. The examiner can normally be reached Monday - Friday 8:00am - 5:00pm EST.
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/SARAH COOPER PATTERSON/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675