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 8/19/2025 wherein claims 2-78 were canceled and claims 79-94 were added. In addition, the Examiner acknowledges receipt of the amendment filed 8/25/2022.
Note(s): Claims 1 and 79-94 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
Independent claim 1 is directed to a nanoemulsion formulation comprising a surfactant, a perfluorocarbon, and a hydrophilic anchor wherein said perfluorocarbon is conjugated to said hydrophilic anchor via linker.
Applicant’s Election
Applicant’s election of Group I (pending claims 1 and 79-94) in the reply filed on 8/19/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)). Thus, the restriction is deemed proper and is made FINAL.
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
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wherein Z = an unsubstituted alkyl. Claims 1 and 79-94 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 because prior art was found which could be used to reject the claims.
Information Disclosure Statement
The information disclosure statement filed 8/26/2022 was considered.
Written Description Rejection
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 1, 79-82, and 84-94 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.
Applicant is reminded that an inventor is entitled to a patent to protect his work only if he/she produces or has possession of something truly new and novel. The invention being claimed must be sufficiently concrete so that it can be described for the world to appreciate the specific nature of the work that sets it apart from what was before. The inventor must be able to describe the item to be patented with such clarity that the reader is assured that the inventor actually has possession and knowledge of the unique composition that makes it worthy of patent protection. The pending application does not sufficiently describe the invention as it relates to linkers other than those of Figure 17:
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wherein Z =
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, a substituted phenyl ring, a heterocyclic ring, an alkyl, a unsubstituted alkyl, an alkene, and sugars used in combination with the nanoemulsion formulations. The specification (page 13, paragraph [0071]) discloses that the linker molecules used to separate chemically dissimilar molecules in the co-surfactant are those in Figure 17. Thus, what the reader gathers from the instant application is a desire/plan/first step for obtaining a desired result. While the reader can certainly appreciate the desire for achieving a certain end result, establishing goals does not necessarily mean that an invention has been adequately described.
While compliance with the written description requirements must be determined on a case-by-case basis, the real issue here is simply whether an adequate description is necessary to practice an invention described only in terms of its function and/or based on a disclosure wherein a description of the components necessary in order for the invention to function are lacking. In order to satisfy the written description requirement, the specification must describe every element of the claimed invention in sufficient detail so that one of ordinary skill in the art would recognize that the inventor possessed the claimed invention at the time of filing. In other words, the specification should describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that the inventor created what is the claimed. Thus, the written description requirement is lacking in the instant invention since the various terms as set forth above are not described in a manner to clearly allow persons of ordinary skill in the art to recognize that Applicant invented what is being claimed.
112 Second Paragraph Rejections
The following is a quotation 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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1 and 79-94 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 79-94: Independent claim 1 is ambiguous because it appears that the nanoemulsion formulation should include be listed as one of the components. However, the claim indicates that the perfluorocarbon is conjugated to the anchor via a linker. For clarity of the claim because the linker is required, it is respectfully suggested that one considers adding it the required components list (surfactant, perfluorocarbon, hydrophilic anchor, and linker). One could possibly write the claim as follows: “A nanoemulsion formulation comprising a surfactant, a perfluorocarbon, a hydrophilic anchor, and a linker wherein said perfluorocarbon is conjugated to said hydrophilic anchor via a linker.” Since claims 79-94 depend upon independent claim 1 for clarity, those claims are also vague and indefinite.
Claim 79: The claim as written is ambiguous because (1) the claim is directed to both a product (hydrophilic anchor) and active steps (the anchor interacts with one or more cells); (2) the claim appears to exclude some of the anchors from claim 1 by only being directed to those which interact with one or more cells. According to MPEP 2173.05(p), a single claim containing both product limitations and active steps is indefinite. Thus, it is unclear what the actual interpretation of the claim should be and what particular anchors interact with cells and which do not. Furthermore, since the nanoemulsion is a pharmaceutical composition according to the disclosure, it is unclear how a pharmaceutical composition would not at some point come in contact with cells.
Claim 81: The claim is ambiguous because of the phrases ‘rich in lysine, arginine, and histidines’, ‘small molecule ligand that binds to a specific cell surface receptor or target cell type’, and ‘a moiety useful for enhanced endocytosis or cell adhesion’. The phrases are ambiguous because one cannot determine the metes and bounds of the claims and/or the phrases are not defined in the claim and neither does the specification does not provide a standard for ascertaining the requisite degree. Thus, one of ordinary skill in the art would not be reasonably apprised of the scope of the invention.
Claim 83: Did Applicant intend to use ‘comprising’ instead of ‘is’ for the linker? Specifically, the linker is not an aliphatic hydrocarbon linker, but according to the disclosure, the linkers are those of Figure 17 which has the formula
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wherein one value of Z is and aliphatic hydrocarbon. Applicant is respectfully requested to clarify the claim in order that one may readily ascertain the scope of the pending invention.
102/103 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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
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, 79, 81, 83, 85, and 86 are rejected under 35 U.S.C. 102((a)(1)) as anticipated by or, in the alternative, under 35 U.S.C. 103 as obvious over Temme et al (Circulation, 2015, Vol. 131, pages 1405-1414) as evidenced by Lund University (Science Daily, 2017, 3 pages, https://www.sciencedaily.com/releases/2017/06/170601095333.htm#) and Orgeig et al (Comparative Biochemistry and Physiology, Part A, 2001, pages 75-89).
Independent claim 1 is directed to a nanoemulsion formulation comprising a surfactant, a perfluorocarbon, and a hydrophilic anchor wherein said perfluorocarbon is conjugated to said hydrophilic anchor via linker.
Claim 81 is directed to a hydrophilic anchor that is a cell penetrating peptide, peptide rich in lysine, arginine, and histidine, a peptide, a small molecule, an oligonucleotide, an antibody, a nanobody, an aptamer, or any moiety that is useful for enhanced endocytosis or cell adhesion.
Claim 83 is directed to the linker comprising an aliphatic hydrocarbon.
Temme et al is directed to targeted perfluorocarbon nanoemulsions (PFCs) that may be labeled with 19F. The targeting anchor is alpha2-antiplasmin peptide. 19F together with alpha2-antiplasmin-targeted perfluorocarbon nanoemulsion is crosslinked to fibrin (see entire document, especially, abstract). The PFCs are generated using a 14-amino acid peptide derived from alpha2-antiplasmin peptide that is crosslinked to fibrin at the glutamine Q3 position. The peptide was further functionalized with a cysteine residue at amino acid position 13 for coupling to the cholesterol-PEG anchor. The peptide was then added to the cholesterol-PEG2000-maleimide anchor. The cholesterol anchor was used in 10-fold excess compared to the ligand (page 1406, left and right column, bridging paragraph; page 1406, right column, ‘Coupling of α2AP to the cholesterol-PEG anchor’; page 1407, Figure 1A). Thus, resulting in a nanoemulsion formulation comprising a perfluorocarbon, a hydrophilic anchor conjugated to a linking moiety, and cholesterol (surfactant).
The Lund University document is made of record as an evidentiary reference that in the pharmaceutical art, cholesterol has surfactant properties and as such and as such it would inherently behave as a surfactant in the nanoemulsion thereof. Specifically, Professor Emma Sparr indicated that her team has obtained astonishing clear results, cholesterol constitutes a natural ingredient in the thin surfactant that is present in the lungs. It is disclosed that researchers were evaluated how cholesterol affects the molecular structure of the thin film in the lungs. The team concluded that the effect of cholesterol on the surface of the alveoli is very clear and could eventually be included in the clinical preparation as it makes sense as our own bodily surfactant contains significant levels (see entire document).
Like Lund University, Orgeig et al, disclose that in some mammals (e.g., eutherian) cholesterol comprises approximately 8-10% or 14-20 mole% of both alveolar and lamellar body surfactant (see entire document, especially, page 75, abstract). Thus, it would have been obvious to one of ordinary skill in the art prior to Applicant’s effective filing date that cholesterol may behave as a surfactant based on the teachings of Orgeig et al.
As set forth supra, Temme et al, like the pending invention, disclose a nanoemulsion formulation comprising a perfluorocarbon, a hydrophilic anchor conjugated to a linking moiety, and cholesterol (surfactant). Thus, both inventions disclose overlapping subject matter. Alternatively, if it is asserted that cholesterol is not a surfactant, according to both Lund University and Orgeig et al, cholesterol was found to behave as a surfactant and considered as the surfactant in the research that was conducted by both teams performing research conducted by Lund University and Orgeig et al. Hence, it would have been obvious to the skilled artisan that Applicant’s invention is obvious when cholesterol behaves as the surfactant in the nanoemulsion. For the reasons herein, the limitations of independent claims 1, 81, and 83 are met.
Claim 79 is directed to the hydrophilic anchor that interacts with one or more cells.
Temme et al disclose the perfluorocarbon nanoemulsion are used for imaging thrombosis in vivo (page 1405, Abstract; page 1406, right column, ‘Animal Experiments’; pages 1406-1407, bridging paragraph). Thus, the limitation of claim 79 is met.
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.
Temme et al disclose that 19F was conjugated to the PFCs and used for MRI studies (page 1405, abstract; page 1407, Figure 1B; page 1407, ‘MRI Studies’ and ‘In Vitro Thrombus Studies’). Thus, the limitations of claims 85 and 86 are met.
Conclusion
Claims 1 and 79-94 are rejected.
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.
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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.
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/D. L. Jones/
Primary Patent Examiner
Art Unit 1618
November 26, 2025