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 .
Acknowledgments and Claim Status
The Examiner acknowledges receipt of the amendment filed 5/1/2026 wherein claims 2-79 were canceled; claims 1, 81-84, 88, and 90; and claim 95 was added.
Note(s): Claims 1 and 80-95 are pending.
Priority
This application is a 371 of PCT/US20/45279 filed 8/6/2020 and PCT/US20/45279 claims benefit to PRO 62884111 filed 8/7/2019.
Note(s): The earliest effective filing date is 8/6/2020 as the pending invention is fully disclosed in both the PCT application and provisional applications.
Claim Interpretation
Amended independent claim 1 is directed to a nanoemulsion formulation comprising a surfactant, a perfluorocarbon, a linker, and a hydrophilic anchor wherein said perfluorocarbon comprises perfluoropolyether (PFPE) or perfluoro-15-crown-5-ether (PFCE), said hydrophilic anchor is selected from a cell penetrating peptide, an oligonucleotide, an antibody, a nanobody, and an aptamer, and said perfluorocarbon is conjugated to said hydrophilic anchor via said linker.
Applicant’s Election
Once again, it is duly noted that Applicant was respectfully requested to elect a surfactant of which none was elected in the response filed 17/630,286. However, Applicant did elect other components: a perfluoropolyether (PFPE) perfluorocarbon; TAT as the cell penetrating peptide hydrophilic anchor; and a linker of Figure 17 wherein Z = an unsubstituted alkyl. From Figure 17, the linker is
PNG
media_image1.png
108
150
media_image1.png
Greyscale
wherein Z = an unsubstituted alkyl. All of the pending claims read on the elected species. Initially, the elected species was searched. Since prior art was not found to reject the claims, the search was extended to the species cited in the prior art rejection below. The search was not further extended over the full scope of independent claim 1 because prior art was found which could be used to reject the claims.
Response to Applicant’s Amendment and/or Arguments
The Applicant's arguments and/or amendment filed 5/1/2026 to the rejection of claims 1 and 79-94 made by the Examiner under 35 USC 102, 103, and/or 112 have been fully considered and deemed persuasive because Applicant amended the claims to overcome the rejection. Thus, all outstanding rejections are WITHDRAWN.
NEW GROUNDS OF REJECTION
103 Rejection
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 (i.e., changing from AIA to pre-AIA ) 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.
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 for establishing a background for determining obviousness under 35 U.S.C. 103 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1 and 80-95 are rejected under 35 U.S.C. 103 as being unpatentable over Ahrens et al (US Patent No. 9,352,057) in view of Arifin et al (Biomaterials, 2019, Vol. 221, No. 119410, pages 1-6).
Pending independent claim 1 is directed to is directed to a nanoemulsion formulation comprising a surfactant, a perfluorocarbon, a linker, and a hydrophilic anchor wherein said perfluorocarbon comprises perfluoropolyether (PFPE) or perfluoro-15-crown-5-ether (PFCE), said hydrophilic anchor is selected from a cell penetrating peptide, an oligonucleotide, an antibody, a nanobody, and an aptamer, and said perfluorocarbon is conjugated to said hydrophilic anchor via said linker.
Claim 80 is directed to the nanoemulsion of claim 1 wherein said hydrophilic anchor is at an amount of at least 2% (w/w) of said hydrophilic anchor to said surfactant.
Claim 81 is directed to a hydrophilic anchor that is a cell penetrating peptide.
Claim 82 is directed to the nanoemulsion of claim 1 wherein the perfluorocarbon comprises PFPE.
Claim 83 is directed to the linker comprising an aliphatic hydrocarbon.
Claim 84 is directed to the nanoemulsion of claim 1 wherein the surfactant comprises a block copolymer of polyethylene and polypropylene glycol.
Claim 85 is directed to the nanoemulsion further comprising a detectable moiety.
Claim 86 is directed to the detectable moiety being attached to the perfluorocarbon.
Claim 87 is directed to the nanoemulsion of claim 85 wherein the detectable moiety is a fluorescent moiety.
Claim 88 is directed to a nanoemulsion comprising a poloxamer surfactant, PFPE or PFCE, a TAT peptide of HIV hydrophilic anchor, and a linker.
Claim 89 is directed to the nanoemulsion of claim 88 wherein said TAT peptide is an amount of at least 2% (w/w) of TAT peptide to surfactant.
Claim 90 is directed to the nanoemulsion comprising a poloxamer surfactant, PFPE, a TAT peptide, and a linker.
Claim 91 is directed to the nanoemulsion of claim 90 wherein the TAT peptide is an amount of at least 2% (w/w) of TAT peptide to surfactant.
Claim 92 is directed to the nanoemulsion of claim 90 wherein said TAT peptide is an amount of at least 2% (w/w) of TAT peptide to surfactant.
Claim 93 is directed to the nanoemulsion of claim 92 wherein said detectable moiety is attached to said perfluorocarbon.
Claim 94 is directed to the nanoemulsion of claim 92 wherein said detectable moiety is a fluorescent moiety.
Claim 95 is directed to the nanoemulsion of claim 1 wherein said perfluorocarbon comprises PFCE.
Ahrens et al is directed to emulsion compositions that may be used to evaluated transplanted cells in a subject (see entire document, especially, abstract; columns 3-4, bridging paragraph). In particular, the composition comprises perfluoro-15-crown-5 ether (PFCE) or perfluoropolyether (PFPE), a surfactant co-mixture, and emulsifier, and an additive (see entire document, especially, column 2, lines 26-29; column 3, lines 7-35; columns 20-21, bridging paragraph). PFCE or PFPE is present in the range of 20%-50% w/v (column 2, lines 36-46). The compositions may also contain propylene glycol (surfactant) in the range of 1%-10% w/v. In a preferred embodiment, the surfactant (e.g., propylene glycol) co-mixture is 2% w/v. Another embodiment has a co-mixture comprising lecithin, cholesterol, and dipalmitoyl phosphatidyl ethanol amine (DPPE) in the range of 1%-10% w/v (column 2, lines 52-64).
The composition may further comprise protamine sulfate, a crosslinker according to Afirin et al (discussion of Afirin et al is found below). The emulsion has a mean droplet size of less than 200 nM in diameter (column 3, lines 43-46). Figures 2-4, 7, 9, and 8 are all directed to nanoemulsions that may be labeled with a detectable component (e.g., fluorescent dye).
In a preferred embodiment, a targeting moiety may be bound to an imaging agent to facilitate selective targeting of the imaging reagent to a particular population of cells (column 6, lines 30-35). Imaging agents may be coupled to targeting agents such as antibodies and HIV TAT peptides (column 13, lines 53-60; column 14, lines 16-20, 24-26, and 47-48; column 21, lines 52-65). The targeting agents may be bound directly or indirectly to the substrate (column 25, lines 17-31; columns 25-26, bridging paragraph).
In a preferred embodiment, Ahrens et al disclose a composition comprising PFPE or PFCE, a surfactant co-mixture (lecithin, cholesterol, and DPPE), an emulsifier, and an additive (propylene glycol) (columns 14-15, bridging paragraph; column 15, lines 31-63; columns 15-16, bridging paragraph; column 16, lines 7-41; columns 37). The compositions of Ahrens et al may also include a poloxamer surfactant (e.g., Pluronic F68 which is also known as BASF and Lutrol F68/Poloxamer 188) (column 16, lines 42-54; column 17, lines 12-38; column 19, lines 7-51; column 37, lines 60-61; column 26, lines 55-62). In the Examples, Ahrens et al disclose that the nanoemulsions are prepared with PECE, protamine sulfate (crosslinker), co-surfactants , and optionally in combination with substances like polyethylene glycol, propylene glycol, and fluorescent dyes (column 37, line 16 through column 40, line 13; column 41-42, bridging paragraph; column 42, lines 18-38). Furthermore, while patented claim 1 (column 45) disclose that the fluorine containing imaging agent contains PFPE or PFCE, glycerol poly ethylene glycol ricinoleate, a surfactant co-mixture, and an additive, that the claimed pated ligand lacks a targeting moiety, column 6 (lines 32-35) disclose that another embodiment incorporates a targeting moiety that facilitates selective targeting of the imaging reagent to a particular population of cells. Thus, the pending claims are rendered obvious by the cited prior art as explained supra.
Arifin et al is directed to fluorocapsules that may be encapsulated by cell transplants. The fluorocapsules are synthesized by embedding emulsion of perfluoro-15-crown-5-ether (PFCE) into a dual alginate gel capsule. Protamine sulfate is used as a crosslinker and barium ions for alginate gelation to generate dual layer fluorocapsules (see entire document, especially, abstract; page 2, left column, first complete paragraph; page 2, left column, second complete paragraph).
The alginate capsules may be labeled with metallic contrast agents such as iron oxide nanoparticles and gadolinium nanoparticles (page 2, right column, first complete paragraph). Due to hydrophobicity, PFCE was emulsified using egg yolk derived lecithin (surfactant) and safflower oil to result in the stable and homogeneous incorporation and distribution of the mixture inside alginate (crosslinker) capsules (page 2, left column, second complete paragraph; page 3, left and right columns, bridging paragraph).
It would have been obvious to the skilled artisan prior to Applicant’s effective filing date to combine Ahrens et al and Arifin et al because both documents are directed to emulsions comprising a perfluorocarbon, a linker, and a surfactant that may be utilized by cell transplants. Thus, the documents may be considered to be within the same field of endeavor. In addition, Arifin et al was made of record to illustrate that the composition disclosed in Ahrens et al is well known as in the art and that certain components such as protamine sulfate (alginate protamine) is the crosslinker in the composition (see Afirin et al, abstract; page 2, left column, first complete paragraph; page 2, left column, second complete paragraph). Hence, the reference teachings are combinable.
For the reasons set forth supra, the claims are rendered obvious by the cited prior art.
Comments/Notes
US Patent Nos. 8,263,043 (Ahrens et al) and 8,147,806 by Ahrens et al are equivalent to US Patent No. 9,352,057 (Ahrens et al) which is cited in the 103 rejection above.
Conclusion
Claims 1 and 80-95 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.
Future Correspondences
Any inquiry concerning this communication or earlier communications from the examiner should be directed to D L Jones whose telephone number is (571)272-0617. The examiner can normally be reached M-F.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael G. Hartley can be reached at (571)272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
July 24, 2026
Prosecution Insights