DETAILED ACTION
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 .
Election/Restrictions
Applicant’s election with traverse of Group I and without traverse of species of the compound of formula IB and perfluoropentane in the reply filed on January 19, 2026 is acknowledged.
The traversal is on the ground(s) that Groups I-III share a special technical feature because the prior art fails to disclose the molar ratio between biocompatible surfactant and fluorocarbon is higher than 0.06 as recited in instant claims. This is not found persuasive because the ratio is a result effective parameter that a person of ordinary skill in the art would routinely optimize as discussed below (Claim Rejections - 35 USC § 103). “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See MPEP § 2144.05. Common technical feature does not qualify as a special technical feature.
The requirement is still deemed proper and is therefore made FINAL.
Drawings
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they do not include the following reference sign(s) mentioned in the description: core portion 100 (¶ 260 of PGPub of instant application). Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Appropriate correction is required.
Specification
The disclosure is objected to because of the following informalities:
The use of the terms NxGen™, NanoAssemblr®, and Zetasizer® which are a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Interpretation
Claim 19 is a product-by-process claim.
[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted) MPEP § 2113.
Claim Objections
Claims 2, 8 and 19 are objected to because of the following informalities:
Claim 2 fails to end with a period as required.
In claim 8, “…claim 6 further…” should read “…claim 6, further…”
In claim 19, “ii)…and a fluorocarbon.” should read “ii)…and a fluorocarbon;”
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph
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, 2, and 4-8 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.
Claim 1 recites “(Dendri-TAC)”, “(F-TAC)”, and “(n=DPn is the average degree of polymerization)”. These terms are indefinite because 1) it is unclear why the terms are in parentheses and 2) as written they appear to be preferred embodiments and if stated in the claims, examples and preferences may lead to confusion over the intended scope of a claim.
The dependent claims fall therewith.
Clarification and/or amendment is required.
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.
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, 2, and 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Desgranges et al. (US 10,286,091, 2019; cited on PTO-892) in view of Astafyeva et al. (Journal of Materials Chemistry B, 2015; cited on IDS filed May 9, 2023).
Regarding claims 1 and 4, Desgranges discloses a nanoparticle comprising a core containing a perfluorocarbon compound and a shell composed of amphophilic dendrimers for diagnostic and/or therapeutic use (claim 19; abstract). Regarding claims 1 and 2, Desgranges discloses that the amphophilic dendrimers can be DiF6 G0DiTAC (w*2) (w: 1-20) (claim 6; column 14, line 16), reads on the compound of formula IB in claim 2 and metes the limitation of outer layer comprising a biocompatible fluorinated surfactant in claim 1. Regarding claim 6, Desgranges discloses a nanoemulsion comprising an aqueous phase, a perfluorocarbon compound, and an amphophilic dendrimer surfactant (claim 7), reads on the aqueous suspension of instant claims. Regarding claims 1 and 5, Desgranges discloses that the droplet size decreases when the ratio of surfactant and protoporphyrin IX in perfluorocarbon core increases (column 116, lines 2-13).
Desgranges does not disclose that the molar ratio between surfactant and fluorocarbon is higher than 0.06 or 0.07.
Astafyeva disclosed perfluorocarbon nanodroplets stabilized by fluorinated surfactants for theranostics use (title). Astafyeva discloses the effect of the surfactant to perfluorocarbon molar ratio on stabilized droplet diameter (page 2899, Fig. 4). Astafyeva discloses that an increase in the ratio results in a decrease in droplet diameter (page 2899, ¶ 2). Astafyeva discloses that an increase in the ratio results in a decrease in droplet diameter (page 2899, ¶ 2). Astafyeva discloses that the additional surfactant leads to stabilization bubbles and at high molar ratio(> 0.006) and coalescence is suppressed by surfactant (page 2903, column 2, ¶ 3; page 2904, column 1, ¶ 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the aqueous suspension of Desgranges by adjusting the ratio between surfactant and fluorocarbon. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Desgranges and Astafyeva teach that the surfactant to fluorocarbon ratio is an important parameter and the ratio can be adjusted to control the droplet diameter and stability. The ratio is 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 ordinary skill to determine the optimal ratio between surfactant and fluorocarbon for achieving the desired droplet characteristics such as droplet diameter and stability. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” See MPEP § 2144.05.
Claims 7 and 19 are rejected under 35 U.S.C. 103 as being unpatentable over Desgranges et al. (WO 2016 185425; cited on IDS filed May 9, 2023) and Astafyeva et al. (Journal of Materials Chemistry B, 2015; cited on IDS filed May 9, 2023) as applied to instant claims 1, 2, 4, 5, and 6 above, and further in view of Martin et al. (Langmuir. 2019; cited on PTO-892).
Regarding claim 7, in addition to the teachings of Desgranges and Astafyeva discussed above, Desgranges discloses the droplets having a mean diameter of 134.9 nm and low polydispersity (page 83, lines 23-25).
Desgranges and Astafyeva do not disclose a polydispersity lower than 0.25.
Martin discloses fluorocarbon nanodroplets having diameters ranging from 100 to 400 nm for a variety of medical applications (abstract). Martin discloses that the nanodroplets can be stabilized by fluorosurfactant and can have a Z-average diameter of 180 ± 3 nm with a polydispersity index of 0.06 ± 0.01 (page 4607, Table 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the aqueous suspension of Desgranges and Astafyeva such that the nanodroplets have a polydispersity index lower than 0.25. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Martin teaches that low polydispersity index can be achieved in fluorosurfactant-stabilized nanodroplets for medical applications. Further, a person of ordinary skill in the art would have been motivated to achieve low polydispersity in order to obtain homogeneous nanodroplets.
Claim 19 is a product-by-process claim. The determination of patentability is based on the product itself and does not depend on its method of production. Claim 19 reads on the product (aqueous suspension) of Desgranges, Astafyeva, and Martin. As discussed above, the aqueous suspension of Desgranges, Astafyeva, and Martin possesses the same characteristics as the aqueous suspension in claims 7 and 19. The aqueous suspension of Desgranges, Astafyeva, and Martin is the same product as would be produced by the process of claim 19. Therefore, claim 19 is not patentably distinguished over Desgranges and Astafyeva further in view of Martin.
Claim 8 is rejected under 35 U.S.C. 103 as being unpatentable over Desgranges et al. (WO 2016 185425; cited on IDS filed May 9, 2023) and Astafyeva et al. (Journal of Materials Chemistry B, 2015; cited on IDS filed May 9, 2023) as applied to instant claims 1, 2, 4, 5, and 6 above, and further in view of Abdelwahed et al. (Advanced Drug Delivery Reviews, 2006; cited on PTO-892).
Desgranges and Astafyeva are discussed above.
Desgranges and Astafyeva do not disclose the aqueous suspension further comprising trehalose.
Abdelwahed discloses the use of trehalose as a cryoprotectant agent for successful freeze-drying nanoparticles (page 1694, Table 2). Abdelwahed discloses that trehalose can be a preferred cryoprotectant for biomolecules because it has many advantages in comparison with the other cryoprotectant agents such as less hygroscopicity, an absence of internal hydrogen bounds which allows more flexible formation of hydrogen bonds with nanoparticles during freeze-drying, very low chemical reactivity, and higher glass transition temperature (page 1694, column 1, ¶ 2).
It would have been obvious to a person of ordinary skill in the art before the effective
filing date of the claimed invention to modify the aqueous suspension of Desgranges and Astafyeva to include trehalose as a cryoprotectant agent. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Abdelwahed teaches trehalose can be used as an effective cryoprotectant agent for the successful freezing of nanodroplets. Further, a person of ordinary skill in the art would have been motivated to include trehalose in the aqueous suspension to improve the freezing efficiency, maintain initial nanodroplet sizes, and ensure a substantially monodispersed distribution over time. Accordingly, applying the teaching of Abdelwahed to the aqueous suspension of Desgranges and Astafyeva constitutes no more than the predictable use of prior art elements according to their established functions, thus rendering claim 8 obvious.
Double Patenting
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 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); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(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 filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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 eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 2, 4-8, and 19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 7, and 19 of U.S. Patent No. US 10,286,091 B2 (cited on PTO-892) in view of Martin et al. (Langmuir. 2019; cited on PTO-892) and Abdelwahed et al. (Advanced Drug Delivery Reviews, 2006; cited on PTO-892).
Regarding claims 1 and 4, claim 19 of the ‘091 recites a nanoparticle comprising a core containing a perfluorocarbon compound and a shell composed of amphophilic dendrimers. Regarding claims 1 and 2, claims 1 and 6 of the ‘091, recites the amphophilic dendrimers can be DiF6 G0DiTAC (w*2) (w: 1-20). Regarding claim 6, claim 7 recites a nanoemulsion comprising an aqueous phase, a perfluorocarbon compound, and an amphophilic dendrimer surfactant.
Regarding claims 1 and 5, the claims of the ‘091 does not disclose that the molar ratio between surfactant and fluorocarbon is higher than 0.06 or 0.07.
As discussed above, the ratio between surfactant and fluorocarbon is 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 ordinary skill to determine the optimal ratio between surfactant and fluorocarbon for achieving the desired droplet characteristics such as droplet diameter and stability.
Regarding claim 7, the claims of the ‘091 do not disclose a polydispersity lower than 0.25.
As discussed above, Martin discloses that the nanodroplets can be stabilized by fluorosurfactant and can have a Z-average diameter of 180 ± 3 nm with a polydispersity index of 0.06 ± 0.01 nm (page 4607, Table 1).
It would have been obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to modify the aqueous suspension of the ‘091 such that the nanodroplets have a polydispersity index lower than 0.25. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Martin teaches that low polydispersity index can be achieved in fluorosurfactant-stabilized nanodroplets for medical applications. Further, a person of ordinary skill in the art would have been motivated to achieve low polydispersity in order to obtain homogeneous nanodroplets.
Regarding claim 8, the claims of the ‘091 do not disclose the aqueous suspension further comprising trehalose.
As discussed above, Abdelwahed discloses the use of trehalose as a cryoprotectant agent for successful freeze-drying nanoparticles (page 1694, Table 2).
It would have been obvious to a person of ordinary skill in the art before the effective
filing date of the claimed invention to modify the aqueous suspension of the ‘091 to include trehalose as a cryoprotectant agent. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Abdelwahed teaches trehalose can be used as an effective cryoprotectant agent for the successful freezing of nanodroplets. Further, a person of ordinary skill in the art would have been motivated to include trehalose in the aqueous suspension to improve the freezing efficiency, maintain initial nanodroplet sizes, and ensure a substantially monodispersed distribution over time.
Claim 19 is a product-by-process claim. The determination of patentability is based on the product itself and does not depend on its method of production. Claim 19 reads on the product (aqueous suspension) of the ‘091 and Martin. As discussed above, the aqueous suspension of the ‘091 and Martin possesses the same characteristics as the aqueous suspension in claims 7 and 19. The aqueous suspension of the ‘091 and Martin is the same product as would be produced by the process of claim 19. Therefore, instant claim 19 is not patentably distinguished over the ‘091 in view of Martin.
Claims 1, 2, 4-8, and 19 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5, and 6 of copending Application No. 18/864,464 (US 2025 0295818; cited on PTO-892) in view of Abdelwahed et al. (Advanced Drug Delivery Reviews, 2006; cited on PTO-892).
Regarding claims 1 and 2, claim 1 of the ‘464 recites a nanodroplet comprising an outer layer comprising a biocompatible fluorinated surfactant such as dendrimer and an inner core comprising a fluorinated compound. Regarding claims 4, claim 2 of the ‘464 recites fluorinated compound is a perfluorocarbon. Regarding claims 6, 7, and 19, claim 5 of the ‘464 recites an aqueous suspension comprising a plurality of nanodroplets, wherein said nanodroplets have a z-average diameter comprised between 100 nm and 1000 nm and a polydispersity lower than 0.25. Regarding claim 19, claim 6 of the ‘464 recites a method for the preparation of an aqueous suspension.
Regarding claims 1 and 5, the claims of the ‘091 does not disclose that the molar ratio between surfactant and fluorocarbon is higher than 0.06 or 0.07.
As discussed above, the ratio between surfactant and fluorocarbon is 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 ordinary skill to determine the optimal ratio between surfactant and fluorocarbon for achieving the desired droplet characteristics such as droplet diameter and stability.
Regarding claim 8, the claims of the ‘464 does not disclose the aqueous suspension further comprising trehalose.
As discussed above, Abdelwahed discloses the use of trehalose as a cryoprotectant agent for successful freeze-drying nanoparticles (page 1694, Table 2).
It would have been obvious to a person of ordinary skill in the art before the effective
filing date of the claimed invention to modify the aqueous suspension of the ‘464 to include trehalose as a cryoprotectant agent. A person of ordinary skill in the art would have been motivated to make these modifications and reasonably would have expected success because Abdelwahed teaches trehalose can be used as an effective cryoprotectant agent for the successful freezing of nanodroplets. Further, a person of ordinary skill in the art would have been motivated to include trehalose in the aqueous suspension to improve the freezing efficiency, maintain initial nanodroplet sizes, and ensure a substantially monodispersed distribution over time.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JONG HWAN BAEK whose telephone number is (571)272-0670. The examiner can normally be reached Mon - Thu, 9 am - 3 pm ET.
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/JONG HWAN BAEK/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618