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 1-8 are pending.
Claims 6-7 are withdrawn.
Claims 1-5 are amended.
Claim 8 is added.
Note, rejections and objections not reiterated from previous office actions are hereby withdrawn. The following rejections or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Rejections - 35 USC § 103
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 1-4 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over HANLEY (Functionalized erythrocyte-derived optical nanoparticles to target ephrin-B2 ligands. Journal of Biomedical Optics. 2019.) in view of YI (WO2020231700A1), TAN (US20190371471A1), GENECARDS (ADAM30. Via Wayback Machine 2020.) and GUO (ITGA2 as a potential nanotherapeutic target for glioblastoma. Scientific Reports. 2019).
Regarding claims 1 and 8, HANLEY teaches a composition comprising:
A delivery vehicle exosome derived from erythrocytes/red blood cells (abstract),
A ligand binding domain is attached to the exosome for the purpose of binding to EphB1 page 2, paragraph 2), which is a marker for at least one port-wine-stain lesional human dermal microvascular endothelial cell (p-hDMVEC) according to Applicant’s specification (Page 14, paragraph 0039). HANLEY teaches that peptides and antibodies can be conjugated to the nanoparticle for the purposes of targeting (page 1, paragraph 2).
the exosome is loaded with indocyanine green (ICG) (abstract), which reads on a therapeutic chromophore
a linker is inserted into the exosome shell to attach the targeting moiety (figure 2), the linker is a DSPE-PEG-CHO (figure 2).
HANLEY does not teach using a normal human dermal microvascular endothelial cell (n-hDMVEC) derived exosome, using an antibody that binds to ADAM 30 or that the linker is DSPE-PEG-COOH.
YI teaches a composition comprising exosomes derived from exosome-producing cells (claim 1), such as human dermal microvascular endothelial cells (claim 6). The exosomes are used to deliver a therapeutic molecule (claim 11). Blood cells can also be used in place of endothelial cells for the invention (page 15, paragraph 0098).
TAN teaches a method of targeting port wine stain (abstract). EPHs and ADAMs are examples of biomarkers that are associated with port wine stain (claim 2). EphB1 is an explicit example (abstract). TAN further teaches that an exosome loaded with a therapeutic with an antibody attached can be used (page 2, paragraph 0008).
GENECARDS teaches that ADAM30 is part of the ADAM family (page 1) and various antibodies can be readily bought to bind to ADAM30 (Page 14-15).
GUO teaches a liposome, which is a species of delivery vehicle, that is conjugated to an antibody (abstract). The antibody is conjugated to the liposome by a DSPE-PEG-COOH linker (page 4, figure 3).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate using a n-hDMVEC-derived exosome. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because exosomes derived from red blood cells and exosomes derived from human dermal microvascular endothelial cells (hDMVECs) are functional equivalents of cell derived exosome drug carriers and the goal of HANLEY is to target receptors on hDMVECs.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate ana antibody for ADAM30. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because EPHs and ADAMS are functional equivalents of biomarkers for port wine stain and ADAM30, which is part of the ADAM family, has readily available antibodies that can be purchased and used.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate a DSPE-PEG-COOH linker. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because a DSPE-PEG-CHO linker and a DSPE-PEG-COOH linker are functional equivalents of pegylated linkers utilized in delivery vehicles for targeting agents commonly used in the pharmaceutical industry.
Regarding claim 2, HANLEY teaches the exosome is loaded with indocyanine green (ICG) (abstract).
Regarding claim 4, HANLEY teaches the method steps as described above. HANLEY further teaches loading the exosomes using a loading buffer and incubation (page 085002-4, paragraph 2) which is passive diffusion. HANLEY further teaches using filtration to separate the exosomes (figure 2 and page 085002-3 paragraph 1).
HANLEY does not teach loading the cargo by sonication or using size exclusion chromatography.
YI teaches loading the exosomes via sonication, which allows for efficient loading of a cargo into the exosomes that results in a membrane without deformation (page 19, paragraph 0113). Passive diffusion and using solvents can also be used as a loading method (page 18, paragraph 0111). YI further teaches the methods for separating the exosomes can include filtration and size exclusion chromatography (page 22, paragraph 0129).
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate loading the cargo by sonication. The person of ordinary skill in the art would have been motivated to make those modifications, because and reasonably would have expected success because passive diffusion and sonication are functional equivalents of loading techniques for cargo into exosomes commonly used in the pharmaceutical industry, furthermore sonication allowed for efficient loading and a membrane without deformation.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate using size-exclusion chromatography. The person of ordinary skill in the art would have been motivated to make those modifications, and reasonably would have expected success because filtration and size-exclusion chromatography are functional equivalents of methods to separate out exosomes used in the pharmaceutical industry.
Note, with regard to claims 1, 3 and 8, these claims recite a composition, and the intended use recited in the preamble would reasonably appear not to be a claim limitation. “If the claim preamble, when read in the context of the entire claim, recites limitations of the claim, or, if the claim preamble is ‘necessary to give life, meaning, and vitality’ to the claim, then the claim preamble should be construed as if in the balance of the claim…If, however, the body of the claim fully and intrinsically sets forth the complete invention, including all of its limitations, and the preamble offers no distinct definition of any of the claimed invention’s limitations, but rather merely states, for example, the purpose or intended use of the invention, then the preamble is of no significance to claim construction because it cannot be said to constitute or explain a claim limitation.” Pitney Bowes, Inc. v. Hewlett Packard Co., 182 F.3d 1298, 1305, 51 USPQ2d 1161, 1165-66 (Fed. Cir. 1999). Thus, the intended use of “wherein, upon irradiation with near-infrared light at a wavelength of approximately 700 nm, the exosome selectively ablates lesional microvasculature relative to adjacent normal vasculature” and “wherein exposure of the novel functionalized endothelial optical exosome to near-infrared laser irradiation at a wavelength of approximately 700 nm, a power density of approximately 100 mW/cm2, for approximately 5 minutes destroys lesional or abnormal blood vessels in a subject while sparing adjacent normal dermal vasculature.” in the composition claims is met by the prior art, because the prior art compositions would be at least capable of performing said use.
Claims 1-5 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over HANLEY (Functionalized erythrocyte-derived optical nanoparticles to target ephrin-B2 ligands. Journal of Biomedical Optics. 2019.) and YI (WO2020231700A1), TAN (US20190371471A1), GENECARDS (ADAM30. Via Wayback Machine 2020.) and GUO (ITGA2 as a potential nanotherapeutic target for glioblastoma. Scientific Reports. 2019) in view of BRUNK (Verteporfin, PDL Treat Port-Wine Stains. Dermatologic Surgery. 2006.).
HANLEY, YI, TAN, GENECARDS and GUO teach Applicant’s invention as discussed above. HANLEY teaches the exosome is loaded with indocyanine green (ICG) (abstract), which can transduce the absorbed light energy to mediate the production of reactive oxygen species (page 085002-6, paragraph 6) and is used for phototherapy (abstract). It is used as a photosensitizer.
Regarding claim 5, HANLEY, YI, TAN, GENECARDS and GUO do not teach using verteporfin.
Regarding claim 5, BRUNK teaches using verteporfin as a photosensitizer to treat port wine stain (abstract).
Note, since the prior art teaches the same method steps it would be inherent that it would result in a loading efficiency of approximately 19%, prior to purification by size-exclusion chromatography.
It would have been obvious to the person of ordinary skill in the art at the time the invention was made to incorporate using verteporfin. The person of ordinary skill in the art would have been motivated to make those modifications, and reasonably would have expected success because verteporfin and ICG are functional equivalents of photosensitizers used in the pharmaceutical industry to treat port wine stain.
The reference does not specifically teach the amounts of Verteporfin and exosomes used as claimed by the Applicant. The amounts of Verteporfin and exosomes is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize. Optimization of parameters is a routine practice that would be obvious for a person of ordinary skill in the art to employ and reasonably would expect success. It would have been customary for an artisan of the ordinary skill to determine the optimal amounts of Verteporfin and exosomes in order to best achieve desired results, such as having enough Verteporfin to achieve a therapeutic effect that it is intended for, a photosensitizer for photodestruction of port wine stain and enough exosomes to encapsulate the Verteporfin and create enough of a composition for use in a patient(s). Thus, absent of some demonstration of unexpected results from the claimed parameters, this optimization of the amounts of Verteporfin and exosomes would have been obvious at the time of Applicant’s invention.
Response to Arguments
Applicant argues the references do not teach the newly amended limitations of the claims, such as targeting ADAM 30 and a DSPE-PEG-COOH linker.
Examiner does not find the argument persuasive because as discussed above TAN, GENECARDS, GUO and BRUNK teach the newly added claimed limitations recited.
Conclusion
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.
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/S.L.M./ Examiner, Art Unit 1618
/Michael G. Hartley/ Supervisory Patent Examiner, Art Unit 1618
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