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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
DETAILED ACTION
Claims 1-27 are pending in this application. This application claims priority to provisional application 63/525,760, filed on 07/10/2023.
Election/Restrictions
Applicant's election with traverse of group I, claims 1-22, and subsequent species election of pan HLA DR-binding epitope as T helper peptide in claim 2 and/or adjuvant imidazoquinoline compound in claim 6 among claims 1-3, 6, 7, 12, 13, and 18-20, polyethylene glycol-modified lipid as the conjugation in claim 9 among claims 8, 9, 12, 13, 18, 19, and cholesterol in claim 11 as structural helper lipid among claims 10-14, in the reply filed on 08/10/2026, is acknowledge.
Applicant’s species election of pan HLA DR-binding epitope as T helper peptide in claim 2 and/or adjuvant imidazoquinoline compound in claim 6 among claims 1-3, 6, 7, 12, 13, and 18-20 is construed as clear admission on the record that pan HLA DR-binding epitope as T helper peptide in claim 2 and/or adjuvant imidazoquinoline compound in claim 6 are obvious variants, if the examiner finds one of the species unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 of the other species.
The traversal is on the ground(s) that there will not be search burden to search both group I and II. This is not found persuasive because
Restriction for examination purposes as indicated is proper because all these inventions are independent or distinct for the reasons given previously and there would be a serious search and examination burden if restriction were not required and the inventions require different search queries as well are likely to raise different non-prior are issues under 35 USC 112(a).
The requirement is still deemed proper and is therefore made FINAL.
Claims 23-27 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a non-elected invention, there being no allowable generic or linking claim.
Claims 1-22 will presently be examined to the extent they read on the elected subject matter of record.
Claim Objections
Claim 15 is objected in the recitation the acronyms “N/P”. Use of the full terminology at the first occurrence would obviate this objection.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of the second paragraph 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.
Claims 4, 6, 9, 11, 12, 15, 17, 18, 19, 20, and 22 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) is considered indefinite, since the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). Note the explanation given by the Board of Patent Appeals and Interferences in Ex parte Wu, 10 USPQ2d 2031, 2033 (Bd. Pat. App. & Inter. 1989), as to where broad language is followed by "such as" and then narrow language. The Board stated that this can render a claim indefinite by raising a question or doubt as to whether the feature introduced by such language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Note also, for example, the decisions of Ex parte Steigewald, 131 USPQ 74 (Bd. App. 1961); Ex parte Hall, 83 USPQ 38 (Bd. App. 1948); and Ex parte Hasche, 86 USPQ 481 (Bd. App. 1949). In the present instance, claims 4, 6, 9, 11, 12, 15, 17, 18, 19, 20, and 22 recite the broad recitations, and claims 4, 6, 9, 11, 12, 15, 17, 18, 19, 20, and 22 also recite narrower statement of the recitations.
Claims 13-15 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Regarding claims 13-15, the phrase “such as” renders the claims indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention.
Claim Rejections - 35 USC § 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.
This application currently names joint inventors. In considering patentability of the claims under 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of 35 U.S.C. 103(c) and potential 35 U.S.C. 102(e), (f) or (g) prior art under 35 U.S.C. 103(a).
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 1-4, 6-9, 12, 16-22 are rejected under 35 U.S.C. 103(a) as being unpatentable over Geest (Lipid-PEG-fentanyl bio-conjugates as a hapten design for lipid nanoparticle templated anti-fentanyl vaccines, https://acs.digitellinc.com/p/s/lipid-peg-fentanyl-bio-conjugates-as-a-hapten-design-for-lipid-nanoparticle-templated-anti-fentanyl-vaccines-522704, 08/23/2022).
Geest teaches lipid nanoparticle (LNP) (the instant claims 1 and 17) comprising fentanyl-poly(ethylene glycol)-dialkyl lipid (the elected species of polyethylene glycol-modified lipid in the instant claims 8, 9, 19) bio-conjugate
having fentanyl haptens on the LNP surface (the instant claims 1 and 19),
having an ionizable cationic lipid (the instant claims 12 and 13) that entraps pan HLA DR-binding epitope PADRE (the instant claims 1, 2, and 20) extended by a decaglutamate amino acid sequence to provide the peptide with an anionic charge (the instant claims 3, 4, and 18) and an imidazoquinoline TLR7/8 agonist (the instant claims 1, 6, and 20) conjugated to a dialkyl lipid inside the LNP (the instant claim 1);
wherein encapsulation in LNP is by hydrophobic interaction (the instant claim 7).
Geest does not teach lipid-polymer nanoparticle (the instant claim 16).
Geest does not specify the particle size (nanoparticle → >0 nm <1000 nm vs about 10-999 nm in the instant claim 22).
This deficiency is cured by the rationale that a prima facie case of obviousness typically exists when the range of a claimed composition lies inside the range disclosed in the prior art, such as in the instant rejection.
The claimed range of particle size is about 10-999 nm and the range of particle size taught in the prior art is >0 nm <1000 nm and therefor, includes the claimed range.
Geest does not specify the number ratio between fentanyl hapten and LNP (Geest’s teaching of NPL containing fentanyl hapten → >0 fentanyl hapten molecule/NPL vs the claimed 1-109 in the instant claim 21).
This deficiency is cured by the rationale that a prima facie case of obviousness typically exists when the range of a claimed composition lies inside the range disclosed in the prior art, such as in the instant rejection.
The claimed range of the number ratio between fentanyl hapten and LNP is 1-109 and the range of the number ratio between fentanyl hapten and LNP taught in the prior art is >0 and therefor, includes the claimed range.
Claims 1-22 are rejected under 35 U.S.C. 103(a) as being unpatentable over Geest (Lipid-PEG-fentanyl bio-conjugates as a hapten design for lipid nanoparticle templated anti-fentanyl vaccines, https://acs.digitellinc.com/p/s/lipid-peg-fentanyl-bio-conjugates-as-a-hapten-design-for-lipid-nanoparticle-templated-anti-fentanyl-vaccines-522704, 08/23/2022) in view of Lysebetten et al. (Lipid-Polyglutamate Nanoparticle Vaccine Platform, ACS Appl. Mater. Interfaces, 10 February 2021; 13 (5): 6011–6022).
The teachings of Geest are discussed above and applied in the same manner.
Geest does not specify the cationic lipid in the instant claim 5, the lipid nanoparticle further comprising cholesterol as a structure helper lipid and phospholipid in the instant claims 10, 11, 13, and 14 and subsequent the N/P (molar ratio of cationic ionizable nitrogen atoms in the cationic ionizable lipid to anionic amino acids in the PADRE conjugate) ratio in LNP in the instant claim 15.
These deficiencies are cured by Lysebetten et al. who teach a lipid-polyglutamate nanoparticle vaccine platform serving as a stand-alone adjuvant and the lipid nanoparticle encapsulates an imidazoquinoline (IMDQ) TLR7/8 agonist as a molecular adjuvant (title, abstract, and conclusion); wherein has a diameter of 200 nm, and comprises within the lipid nanoparticle an ionizable lipid 2-(diisopropylamino)ethanol and distearylamine conjugate (DIPADS, containing nitrogen atoms), cholesterol, and dioleoylphosphatidylethanolamine (DOPE, a phospholipid) as structural helper lipids, and distearoyl-rac-glycerol-poly(ethylene gylcol) (DSG-PEG; PEG length, 2 kDa) (figure 1, scheme 2 and the section under “Lipid-Polyglutamate Nanoparticle Fabrication” on page 6015) and the rationale that a prima facie case of obviousness typically exists when the range of a claimed composition lies inside the range disclosed in the prior art (Geest’s teaching of NPL containing all components in view of Lysebetten et al. → all components >0 mol% and Geest’s teaching of NPL containing anionic amino acids in the PADRE conjugate and DIPADS in view of Lysebetten et al. → numbers of both N and P >0 → N/P >0).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person of ordinary skill in the art to combine the teachings in Geest and Lysebetten et al. to specify the LNP taught by Geest comprising an ionizable lipid DIPADS (the instant claim 5), cholesterol and DOPE as structural helper lipids (the instant claims 10, 11, 13, and 14), and DSG-PEG. A stand-alone lipid-polyglutamate nanoparticle vaccine platform adjuvant comprising an ionizable lipid DIPADS (the instant claim 5), cholesterol and DOPE as structural helper lipids (the instant claims 10, 11, 13, and 14), and DSG-PEG was well known to a person of ordinary skill in the art before the effective filing date of the claimed invention. The motivation for specifying it flows from its having been used in the prior art, and from its being recognized in the prior art as useful for the same purpose.
The claimed range of mol% of the components in claims 13 and 14 are about 0.1 -10 mol % lipid-PEG-fentanyl hapten conjugate; about 20-80 mol % cationic ionizable lipid; about 0.1-10 mol % lipid-TLR agonist conjugate; and about 10-90 mol % structural helper lipid, about 30-45 mol % sterol; and about 5-15 mol % phospholipid and the range of all component taught in the prior art is >0 mol% and therefor, includes the claimed range.
The claimed range of N/P is 3-30:1 and the range of N/P taught in the prior art is >0 and therefor, includes the claimed range.
Claims 1-22 are rejected under 35 U.S.C. 103(a) as being unpatentable over Pravetoni et al. (US 2023/0126276 A1) in view of Lysebetten et al. (Lipid-Polyglutamate Nanoparticle Vaccine Platform, ACS Appl. Mater. Interfaces, 10 February 2021; 13 (5): 6011–6022).
Pravetoni et al. teach fentanyl hapten-carrier conjugate as an anti-opioid vaccine (abstract) comprising
fentanyl hapten conjugated to an immunogenic carrier including liposome (formed by phospholipid comprising a lipid core and a lipid layer surrounding the core in the instant claim 17) nanoparticles (paragraph 72 and 73), i.e., fentanyl haptens on the surface of carrier, (the instant claims 1 and 19); and
an adjuvant or other delivery platform to augment the immunogenicity of the conjugate including toll like receptor (TLR) agonist (paragraph 86 and 90-92).
Pravetoni et al. do not teach lipid-polymer nanoparticle (the instant claim 16)
Pravetoni et al. do not specify the number ratio between fentanyl hapten and LNP (Pravetoni et al.’s teaching of liposome nanoparticles conjugating fentanyl hapten → >0 fentanyl hapten molecule/liposome nanoparticle vs the claimed 1-109 in the instant claim 21).
This deficiency is cured by the rationale that a prima facie case of obviousness typically exists when the range of a claimed composition lies inside the range disclosed in the prior art, such as in the instant rejection.
The claimed range of the number ratio between fentanyl hapten and LNP is 1-109 and the range of the number ratio between fentanyl hapten and LNP taught in the prior art is >0 and therefor, includes the claimed range.
Pravetoni et al. do not specify the particle size (nanoparticle → >0 nm <1000 nm vs about 10-999 nm in the instant claim 22).
This deficiency is cured by the rationale that a prima facie case of obviousness typically exists when the range of a claimed composition lies inside the range disclosed in the prior art, such as in the instant rejection.
The claimed range of particle size is about 10-999 nm and the range of particle size taught in the prior art is >0 nm <1000 nm and therefor, includes the claimed range.
Pravetoni et al. do not specify TLR agonist including the elected species imidazoquinoline as an adjuvant in the instant claims 1-3, 6, 7, 12, 13, and 18-20, claim 15 and claim 12 and 13 which are subsequent limitation of obvious variant of imidazoquinoline, a T helper peptide, discussed above; adjuvant being conjugated to a lipid and said lipid-adjuvant conjugate being encapsulated within the lipid nanoparticle through hydrophobic interaction in the instant claims 7 and 20, fentanyl hapten being conjugated to the lipid nanoparticle via a PEG-lipid in the instant claims 8, 9, 12, 13, and 19; and further comprising cholesterol as a structural helper lipid in the instant claims 10, 11, and 14.
These deficiencies are cured by Lysebetten et al. whose teachings are discussed above and applied in the same manner and the rationale that a prima facie case of obviousness typically exists when the range of a claimed composition lies inside the range disclosed in the prior art (Pravetoni et al.’s teaching of lipid nanoparticle containing all components in view of Lysebetten et al. → all components, except a T helper peptide and subsequent limitations of about 20-80 mol % cationic ionizable lipid, >0 mol%).
It would have been prima facie obvious before the effective filing date of the claimed invention to a person of ordinary skill in the art to combine the teachings in Pravetoni et al. and Lysebetten et al. to specify TLR agonist including imidazoquinoline; adjuvant being conjugated to a lipid and said lipid-adjuvant conjugate being encapsulated within the lipid nanoparticle through hydrophobic interaction; fentanyl hapten being conjugated to the lipid nanoparticle via a PEG-lipid; and the liposome nanoparticles further comprising cholesterol as a structural helper lipid. A stand-alone lipid-polyglutamate nanoparticle vaccine platform adjuvant comprising TLR agonist including imidazoquinoline; adjuvant being conjugated to a lipid and said lipid-adjuvant conjugate being encapsulated within the lipid nanoparticle through hydrophobic interaction; fentanyl hapten being conjugated to the lipid nanoparticle via a PEG-lipid; and the liposome nanoparticles further comprising cholesterol as a structural helper lipid was well known to a person of ordinary skill in the art before the effective filing date of the claimed invention. The motivation for specifying it flows from its having been used in the prior art, and from its being recognized in the prior art as useful for the same purpose.
The claimed range of mol% of the components in claims 13 and 14 are about 0.1 -10 mol % lipid-PEG-fentanyl hapten conjugate; about 0.1-10 mol % lipid-TLR agonist conjugate; and about 10-90 mol % structural helper lipid, about 30-45 mol % sterol; and about 5-15 mol % phospholipid and the range of all component taught in the prior art is >0 mol% and therefor, includes the claimed range.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HONG YU whose telephone number is (571)270-1328. The examiner can normally be reached on 9 am - 5:30 pm.
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/HONG YU/
Primary Examiner, Art Unit 1614
