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 .
Claims 1-16 are pending, as originally filed and are considered herein.
Formalities:
The specification is accepted.
The drawings of 6/5/23 are accepted.
The present Application, filed 6/5/23, is a CON of 17/559,620 (now US 11,707,528), filed 12/22/21, which is a CON of PCT/CN2020/123993, filed 10/27/20, which claims priority to CN document 202010629898.4, filed 7/1/20.
No IDSs have been filed in the present Application, to date.
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 8-16 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. 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.
Claims 8-13 are to a generic administration of an mRNA-polyA-mannose to a subject in generic need thereof. Claims 9 and 12 are to parenteral, oral, or intra-tumoral administration, and Claim 10 indicates that he subject may have a tumor or pathogen. Comparing these claims to Claims 14-16, these claims must also cover subject matter in which an immune response is not triggered or activated. Claims 14-16 are generic for the triggers and activations of generic immune responses, in the body. As far as the generic disorders and diseases and conditions encompassed by doing this to a generic subject “in need thereof”, while claims hint at tumors and pathogens, or melanoma (Claims 10, 13, and 16), but there is no requirement for the same, even in the claim, as it can be just suspicion. This is not measurable, and thus, not required, as it would require accessing the mind of the Artisan.
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.
As far as the diseases/disorders/conditions that would place a subject “in need thereof”, the specification is devoid of diseases/disorders/conditions, and of mechanisms, aside from teaching a single tumor in mice, with a single human melanoma, which are treated to express anti-PD-1 antibodies, thereby prolonging life of the mice so-treated (Example 10).
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.
Further, the cells targeted must express the mannose receptor, in order to transfect them. Thus, if one were to treat a disease, it would be apparent that the cells, or an interacting cell, must express the mannose receptor. However, the mannose receptor is expressed primarily on the surface of macrophages, immature DCs, liver sinusoidal cells, and on dermal fibroblasts and keratinocytes (Wikipedia, Authors unknown, printed 3/21/26, “Mannose receptor”, from Mannose receptor - Wikipedia, no volume or issue, 11 pages). Thus, it is not known how this will most diseases, particularly if it does not involve the particular cells that express the receptor.
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 diseases/disorders/conditions, the wide variety of immune activations and triggers, and the limited types of cells which contain the mannose receptor in the first place, and single showing of treatment of melanoma in immune compromised mice, the Artisan would not have understood Applicant to have been in possession of the invention as claimed.
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.
Claims 7 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-10 of U.S. Patent No. 11,707,528. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Claim 7: The patent teaches the mRNA-mannose conjugate, comprising an mRNA, and polyA tail, linked to a secondary amine, which attaches a mannose.
Thus, the kit is inherently taught, as the components are required to make the conjugates of the patent. The Artisan would make the kit, to make the conjugates claimed. The Artisan would expect success, as the patent claims the conjugate.
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 1-6 are allowable.
Claims 7-16 are rejected.
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