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 .
Applicant’s amendment and argument of 6/25/26 is entered.
Claims 8-9, 11-12, and 14-15 are amended.
Claims 10, 13 and 16 are canceled.
Claims 17-19 are newly presented.
Claims 1-9, 11-12, 14-15 and 17-19 are pending and are considered herein.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 8-9, 11-12, 14-15, and 17-19 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement, under the modified basis herein, due to the amendments. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The claims are generic to expressing a polypeptide in a subject in need, the subject suffering a melanoma, comprising administration of a the mRNA-mannose conjugate having a 3’polyA tail and the mannose attached to the last A of the polyA tail, via a secondary amine (e.g., Claim 8). Claim 9 teaches parenteral, oral, and intra-tumor administration. Clam 11 is parallel to Claim 8, but is to a generic “treating a subject in need”. Claim 12 parallels Claim 8. Claim 14 parallels these claims but is to a generic triggering or activating an immune response, in a subject in need, with a melanoma. Claim 15 is again parallel to Claim 8. New Claims 17-19 depend from each of these independent claims, and claim 7 distinct forms of administration.
The specification discusses medicaments and drugs (e.g., paragraphs 33-36). The technical solution being modified with mannose, the mRNA can be targeted without using a nanoliposomal carrier (e.g., paragraph 36). Essentially, the mannose targets the mannose receptor, on macrophages (paragraph 64), and is endocytosed, dissociating from the receptor under the proton sponge effect, whereby it can enter the cell and be translated into protein (e.g., paragraph 77). Therefore, the mRNA can be targeted to specific cells through the mannose receptor (e.g., paragraph 81). Example 7 demonstrates the intracellular uptake through the mannose receptor. Example 8 shows that it can deliver and express mRNA encoding luciferase, targeting the spleen mainly, when injected intravenously, luciferin being injected IP. Example 10 demonstrates PD-1 antibodies can be expressed this way, to increase melanoma survival in mice. All of these three sets of claims indicate that, within the context of a generic melanoma, a generic subject may be treated through any form of administration, or those specifically claimed in the dependent claims, and that one may, separately, express a polypeptide, treat the subject, trigger an immune response, or activate an immune response. Further, there is no other disclosure as to what other forms of encoded proteins may be used to treat melanomas, although the specification’s examples also teach the use of luciferase as proof of expression.
As far as treating the subject in need, diagnosed with melanoma, there is only a single mention of melanoma in the specification. Example 10 teaches the use of mRNA-mannose conjugates of the same structure, the mRNA encoding an antibody to PD-1. The direct injection of these compositions into the tumor are taught, and shown to improve the survival rate of humanized mice bearing the melanoma, demonstrating the composition is more easily endocytosed and expressed, thereby improving survival. From this, there is no teaching as to how to separately express the peptide, why one would express PD-1 beyond treating the melanoma in this mouse model, no teaching for how to separately treat the subject, without expression, and how to separately activate or trigger an immune response, beyond that of the PD-1/PD-l1 methods known in the art. Further, being only disclosed once, in an embodiment in an example, there is no teaching to lead one to the generic treatment of melanoma in the generic scope of subjects encompassed.
However, there are a great many diseases/conditions/disorders that exist, with distinct cells/tissues affected, and distinct mechanisms of the disease, many of which we do not know the cause (e.g., Keenan, et al. (2017) “Mechanisms and causality in molecular diseases”, History and Philosophy of the Life Sciences, 39(17): 35, 12 pages, see, e.g., section 2, “Most diseases are different; they caused by changes in network states”). In this, sickle cell is focused upon, but it makes clear diseases are different with different pathways and proteins involved, and thus, even if one is known, this does not provide the information for treating a generic disease/condition/disorder.
With regard to the generic claiming of melanoma, the Art recognizes that anti-PD-1 therapy is not known to work on all melanomas, but only that of common skin melanomas (cutaneous), and it is not so effective on ocular or mucosal melanomas (e.g., Nakamura, et al. (2021) “Anti-PD-1 antibody monotherapy versus anti-PD-1 plus anti-CTLA-4 combination therapy as a first-line immunotherapy in unresectable or metastatic mucosal melanoma: a retrospective, multicenter study of 329 Japanese cases (JMAC study)”, ESMO OPEN Cancer Horizaons, 6(6):j.esmoco.2021.1000325, 9 pages long, p. 8, col. 1, last paragraph). Thus, it is clear that a generic melanoma would not be expected to be treatable.
With regard to the immune activations and triggers, such involves a myriad of effects, that vary widely in the proteins and pathways involved. For example, Marshall, et al. (2024) “Introduction to immunology and immune disorders” Allergy, Asthma & Clinical Immunology, 20(Suppl. 3): 69, 11 pages, provides many cell types, molecules involved, and disorders that occur (e.g., Table 4). Yet there is no understanding which cell and which molecule and chemical pathway needs to be affected. In fact, again, many of these cells do not even express the mannose receptor, and thus, would not be expected to express the protein in the first place.
Given the wide variety of subjects and melanomas, wide variety of possible proteins to be encoded, and in which several forms of outcome are claimed separately, and single showing in mice, with only a direct injection, performing all of the purposes together, with a single protein, the Artisan would not have understood Applicant to have been in possession of a generic melanoma in a generic patient, with a generic mRNA, and a generic form of administration, including those separately claimed from direct injection.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
In light of the argument, the rejection of Claims 7 on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,707,528, is withdrawn.
To wit, the present Application is a DIV of the patent’s application, and separated the kits and method of making the conjugate, from the conjugate itself, and the methods of expressing in a subject. There was no rejoinder. Thus, the rejection is properly withdrawn.
Response to Argument – Written Description
Applicant’s argument of 6/25/26 has been considered but is not found persuasive.
Applicant argues that they have amended to the claims to melanoma, and point to Example 10 for support, and therefore state that they have full support for the claims as presently presented.
Such is not persuasive. As seen in the rejection, the Artisan would not reasonably understand possession of a generic melanoma, in a generic patient, with a generic encoded protein, and a generic form of administration, and would not understand possession of each of these effects separately, but only together.
Claims Free of the Prior Art
The claims are free of the prior art. While it is noted that Applicant has filed several applications, both in the USA and foreign, the present Application has the earliest priority, such that the Art presents no issues. For Example EP 4008334 A1 provides for the mannose-labeled mRNA, but does not beat present priority. Further, while the art presents the use of mannose as a ligand for cell entry, it is only associated with carriers for nucleic acids and not linked to an mRNA. For example, Feng, et al. (2021) “Mannose-Modified Chitosan Poly(lactic-co-glycolic acid) Microspheres Act as a Mannose Receptor-Mediated Delivery System Enhancing the Immune Response”, Polymers, 13: 2028, 19 pages, presents mannose-modified Chitosan PLGA microspheres (e.g., ABSTRACT; Section 2.2.6 on page 4), which encapsulate the delivered substance (in this case ovalbumin) (ABSTRACT). However, the Artisan was not motivated from the prior art to arrive at conjugated mRNA for delivery, given the unstable nature of the mRNA and digestion during endocytosis (e.g., p. 16, citing the known “endocytic” activity). On the other hand, Applicant’s own examples demonstrate delivery to the cells, and subsequent expression (e.g., Examples). Thus, while not motivated to make the same for delivery by the prior art, Applicant has shown it can work, and thus, it is also free of the art.
Conclusion
Claims 1-7 are allowable.
Claims 8-9, 11-12, 14-15 and 17-19 are rejected.
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 ROBERT M KELLY whose telephone number is (571)272-0729. The examiner can normally be reached M-F: 8a-5p.
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ROBERT M. KELLY
Examiner
Art Unit 1638
/ROBERT M KELLY/Primary Examiner, Art Unit 1638
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