DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This is the first Office action on the merits of the claims.
The Patent Office has transferred this application to a different examiner. Please direct any reply to the examiner now identified on the cover page.
All citations to the Manual of Patent Examining Procedure (MPEP) refer to Revision 01.2024, which was released in November 2024.
Status of the Claims
In the Reply filed 22 May 2026, Applicant amended claims 44-49, cancelled claims 53-56, and added eleven new claims, i.e., claims 57-67. Claims 1-43 were cancelled previously by Applicant. Claims 44-52 and 57-67 are pending.
Restriction/Election
The examiner acknowledges Applicant’s election of Group I without traverse and notes that Applicant has cancelled all claims directed to non-elected Groups II and III.
The examiner acknowledges Applicant’s election of the following nine species without traverse: (1) cyclic di-AMP, as the DAMP or PAMP; (2) 1,2-dimyristoyl-sn-glycero-3-phosphate (14:0 PA), as the lipid; and (3) Mn2+, as the cation.
Pursuant to 37 CFR 1.142(b), claims 48-49, 52, 58-59, and 62-66 are withdrawn from consideration because they are directed to non-elected species of DAMP/PAMP, lipid, and/or cation.
Claims 44-47, 50-51, 57, 60-61, and 67 are considered below.
Claim Objections
Claims 44-47, 50-51, 57, 60-61, and 67 are objected to because of the following informalities:
Regarding claim 44, the abbreviations “DAMPs” and “PAMPs” are not defined in the claim. Applicant is referred to page 1, lines 24-25, of the as-filed specification, which defines DAMPs as “damage-associated molecular patterns” and PAMPs as “pathogen-associated molecular patterns.”
Regarding claim 45, the abbreviation “STING” is not defined in the claim. Applicant is referred to page 2, line 4, of the as-filed specification, which defines STING as stimulator of interferon genes.
Regarding claims 50 and 61, the abbreviation “DOPE” is not defined in the claims. Applicant is referred to page 5, line 34, of the as-filed specification, which defines DOPE as dioleoylphosphatidylethanolamine.
Regarding claim 57, three chemical structures set forth on page 8 are blurry and, consequently, will not publish correctly in any patent that issues from this application. Specifically, the chemical structures corresponding respectively to gemcitabine, STING-agonist-C11, and STING agonist-1 must be clarified.
Appropriate corrections are required. The remaining claims are objected to because they depend directly or indirectly on one of claims 44-45, 50, 57, and 61.
Claim Rejections - 35 U.S.C. 112(b)
The following is a quotation of 35 U.S.C. 112(b):
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.
Claims 44-47, 50-51, and 67 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter that the inventors regard as the invention.
Regarding claim 44, the following limitation is unclear: “one or more DAMPs or PAMPs.” A person having ordinary skill in the art — even after reviewing the specification of the present application — would not be able to discern with reasonable certainty the scope of the structural or compositional implications of the foregoing functional limitation. Beyond selecting from among the diverse classes and compounds recited in the Markush groups of claims 45, 57 and 60, respectively, how else can the functional profile required by Applicant’s limitation be achieved? The specification provides no guidance on these matters, and persons having ordinary skill in the art would not know with reasonable certainty from the claim terms which, if any, other substances are encompassed by the foregoing functional limitation. Persons having ordinary skill in the art can reasonably differ over where the boundary lies between (i) compounds and other substances that are DAMPs or PAMPs and (ii) compounds and other substances that are neither DAMPs nor PAMPs. MPEP § 2173.04 (“a genus claim that could be interpreted in such a way that it is not clear which species are covered would be indefinite (e.g., because there is more than one reasonable interpretation of what species are included in the claim).”). This ambiguity renders claim 44 indefinite. MPEP § 2173.05(g) (“the use of functional language in a claim may fail ‘to provide a clear-cut indication of the scope of the subject matter embraced by the claim’ and thus be indefinite”). This aspect of the §112(b) rejection additionally applies to dependent claims 46-47, 50-51, and 67. It does not apply to claims 45, 57, and 60-61.
Regarding claim 45, the italicized segment of the following limitation is unclear: “purine containing or purine derived agents.” Emphasis added. The specification of the present application provides no guidance regarding how to distinguish (i) agents that are purine-derived from (ii) those that are not purine-derived. Furthermore, the adjective <derived> is subjective and ambiguous, especially considering neither it nor the noun form (“derivative”) is defined in, or otherwise limited by, the specification. Where is the boundary between the derivatives and the non-derivatives? MPEP § 2173.05(b)(I) (terms of degree). Persons having ordinary skill in the art can reasonably differ regarding which compounds qualify as purine-derived and, conversely, which do not. MPEP § 2173.04 (quoted above). Consequently, claim 45 is indefinite.
Claim Rejections - 35 U.S.C. 103
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.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103(a) are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 44-47, 50-51, 57, 60-61, and 67 are rejected under 35 U.S.C. 103 as being unpatentable over Moon (WO 2020/014644 A1) in view of Bernasconi (“Mucosal vaccine development based on liposome technology.” Journal of immunology research 2016.1 (2016): 5482087).
Moon is directed to metal-containing formulations capable of modulating immune response.
In Example X (pages 105-106), Moon discloses the following formulation: “manganese-CDA-H11-DOPE@lipsome nanoparticles (Mn-CDA/H11@lipsome, Fig 13).” Page 105, lines 32-33; see also Figure 13A (metal ion-polyHis-DOPE@liposome) and Figure 13B (Mn-CDA/H11@liposome). The manganese (Mn) is in the form of the divalent cation: Mn2+. Page 106, lines 1-5; see also page 109 at claim 1. The abbreviation “CDA” stands for cyclic-di-AMP (page 34), which is the species of DAMP or PAMP elected by Applicant. H11-DOPE is a [lipid]-[polyhistidine] conjugate, which is referred to in present claims 50 and 61 as “DOPE-H11.”
Moon discloses that the average size of the nanoparticles is “between 6 to 500 nm.” Page 116 at claim 22; see also page 18, line 20 (same). The foregoing range is overlapped by the corresponding ranges recited in claim 44 (“20 to 500 nm”), claim 46 (“30 to 500 nm”), and claim 67 (“40 to 120 nm”) of the present application. MPEP § 2144.05(I) (“In the case where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists.”).
Example X, itself, does not identify the structural compounds that form the bilayer of liposome, but Moon, on an earlier page, identifies the following combination as the structural constituents of the bilayer: DPPC, cholesterol, and DSPE-PEG5k. Page 102, line 9.
Example X is silent as to whether 1,2-dimyristoyl-sn-glycero-3-phosphate, which is the species of lipid elected by Applicant, can be included in the bilayer of the liposome. The examiner notes that the foregoing phospholipid is commonly referred to in the relevant art as dimyristoylphosphatidylglycerol (DMPG). As explained below, the following reference compensates for this deficiency: Bernasconi.
Bernasconi is directed to mucosal vaccine development based on liposome technology.
Bernasconi teaches: “Combinations of both DPPC/DMPG and DPPC/PS have been found effective at targeting liposomes to macrophages, though DPPC/DMPG were found more immunogenic than liposomes with DPPC/palmitoyl phosphatidylethanolamine (DPPE) or DPPC/PS.” Page 8, left column (emphasis added); see also page 6 at Figure 2 (identifying DMPG as one of three lipids commonly used to generate customized liposomes).
Before the effective filing date of the claimed invention, the foregoing teachings of Bernasconi would have motivated a person having ordinary skill in the art to modify Example X of Moon by adding DMPG to the DPPC-containing mixture used to generate the lipid bilayer, in an effort to increase the immunogenicity of the Mn2+-polyHis-DOPE@liposome formulation. The foregoing modification would have made with a reasonable expectation of success, especially considering that Moon identifies dimyristoylphosphatidylglycerol (DMPG) as an exemplary phospholipid (page 54 at line 4). Therefore, claims 44-47, 50-51, 57, 60-61, and 67 are prima facie obvious.
Claim Rejections - Double Patenting (Non-Statutory)
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 obviousness-type 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); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR1.321(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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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 eTerminalDisclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/ eTD-info-I.jsp.
Claims 44-47, 50-51, 57, 60-61, and 67 are rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-19 of Patent No. 12,622,922 (issued 12 May 2026) in view of Bernasconi (“Mucosal vaccine development based on liposome technology.” Journal of immunology research 2016.1 (2016): 5482087).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following: Conflicting claim 15 of the ’922 Patent is directed to a nanoparticle comprising (i) c-di-AMP, (ii) Mn2+, and (iii) PH-PEG or lipid-polyhistidine. Conflicting claim 3 teaches that the nanoparticle is encapsulated in a liposome, and conflicting claims 18-19 collectively teach that the lipid-polyhistidine is DOPE-H11. Conflicting claim 7 teaches an average particle size of 6 to 500 nm. However, the conflicting claims are silent as to whether the liposome can comprise DMPG. Bernasconi teaches: “Combinations of both DPPC/DMPG and DPPC/PS have been found effective at targeting liposomes to macrophages, though DPPC/DMPG were found more immunogenic than liposomes with DPPC/palmitoyl phosphatidylethanolamine (DPPE) or DPPC/PS.” Page 8, left column; see also page 6 at Figure 2. Therefore, it would have been obvious to modify the conflicting claims by selecting DPPC/DMPG as structural constituents of the liposomal bilayer, to increase the immunogenicity of the formulation. Accordingly, the present claims are not patentably distinguishable over conflicting claims 1-19 of the ’922 Patent.
Claims 44-47, 50-51, 57, 60-61, and 67 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 5, 14, and 16 of co-pending Application No. 18/293,217 (as amended on 24 June 2024) in view of Bernasconi (“Mucosal vaccine development based on liposome technology.” Journal of immunology research 2016.1 (2016): 5482087).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following: Conflicting claim 5 of the ’217 Application is directed in part to a nanoparticle having the following formulation: metal-polyhistidine-DOPE@liposome. Conflicting claim 14 teaches that the nanoparticle comprises the following immunostimulatory agents: c-di-AMP and Mn2+. Additionally, conflicting claim 16 teaches c-di-AMP. However, the conflicting claims are silent as to whether the liposome can comprise DMPG. Bernasconi teaches: “Combinations of both DPPC/DMPG and DPPC/PS have been found effective at targeting liposomes to macrophages, though DPPC/DMPG were found more immunogenic than liposomes with DPPC/palmitoyl phosphatidylethanolamine (DPPE) or DPPC/PS.” Page 8, left column; see also page 6 at Figure 2. Therefore, it would have been obvious to modify the conflicting claims by selecting DPPC/DMPG as structural constituents of the liposomal bilayer, to increase the immunogenicity of the formulation. Accordingly, the present claims are not patentably distinguishable over conflicting claims 5, 14, and 16 of the ’217 Application. This is a provisional rejection because the conflicting claims have not been patented.
Claims 44-47, 50-51, 57, 60-61, and 67 are provisionally rejected on the ground of non-statutory double patenting as being unpatentable over claims 1-43 of co-pending Application No. 19/673,749 (11 May 2026) in view of Bernasconi (“Mucosal vaccine development based on liposome technology.” Journal of immunology research 2016.1 (2016): 5482087).
Although the claims at issue are not identical, they are not patentably distinct from each other because of the following: Conflicting claim 13 of the ’749 Application is directed in part to a nanoparticle having the following formulation: metal-polyhistidine-DOPE@liposome. Conflicting claim 1 teaches that the nanoparticle comprises Mn2+ (as the metal cation) and a DAMP/PAMP. Conflicting claims 8 and 11 teach that c-di-AMP can be selected as the DAMP/PAMP. Conflicting claim 22 teaches an average particle size of 6 to 500 nm. However, the conflicting claims are silent as to whether the liposome can comprise DMPG. Bernasconi teaches: “Combinations of both DPPC/DMPG and DPPC/PS have been found effective at targeting liposomes to macrophages, though DPPC/DMPG were found more immunogenic than liposomes with DPPC/palmitoyl phosphatidylethanolamine (DPPE) or DPPC/PS.” Page 8, left column; see also page 6 at Figure 2. Therefore, it would have been obvious to modify the conflicting claims by selecting DPPC/DMPG as structural constituents of the liposomal bilayer, to increase the immunogenicity of the formulation. Accordingly, the present claims are not patentably distinguishable over conflicting claims 1-43 of the ’749 Application. This is a provisional rejection because the conflicting claims have not been patented.
Conclusion
Claims 44-47, 50-51, 57, 60-61, and 67 are rejected.
Claims 44-47, 50-51, 57, 60-61, and 67 are also objected to.
No claim is allowed.
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/P.A./
21 August 2026
/CRAIG D RICCI/Primary Examiner, Art Unit 1611
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