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 .
DETAILED ACTION
Election/Restrictions
1. Applicant's election of Group I, claims 1-5, without traverse, filed January 13, 2026 is acknowledged and has been entered. Claims 6-16 are withdrawn from further consideration by the examiner, 37 CFR 1.142(b), as being claims drawn to a non-elected invention. Accordingly, claims 1-16 are pending. Claims 1-5 are under examination.
Priority
2. Acknowledgment is made of Applicant's claim for foreign priority based on an application filed in China: CN 2022110772012 on 09/05/2022 and CN 2022111623068 on 09/23/2022. It is noted, however, that Applicant has not filed a certified copy of these foreign applications as required by 37 CFR 1.55. Attempts by the Office to electronically retrieve, under the priority exchange program, the applications to which priority is claimed have failed.
3. Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. 119(b) or 365(b), and 37 CFR 1.55 on the basis of the filing dates of CN 2022110772012 on 09/05/2022 and CN 2022111623068 on 09/23/2022. Based on the filing receipt, the effective filing date of this application is September 5, 2022 which is the filing date of Foreign Application CN 2022110772012 from which the benefit of foreign priority is claimed.
Claim Rejections - 35 USC § 112
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.
4. Claims 1-5 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
As set forth in In re Wands, 858 F .2d 731, 8 USPQ2d 1400 (Fed. Cir. 1988), enablement requires that the specification teach those in the art to make and use the invention without undue experimentation. Factors to be considered in determining whether a disclosure would require undue experimentation include 1) the nature of the invention, 2) the state of the prior art, 3) the predictability or lack thereof in the art, 4) the amount of direction or guidance present, 5) the presence or absence of working examples, 6) the quantity of experimentation necessary, 7) the relative skill of those in the art, and 8) the breadth of the claims.
The nature of the invention:
The invention is directed to a method for removing or eliminating masking effect of protein corona on the surface of nanoparticulate liposomes that have been modified by protein corona in protein-containing conditions during preparation of ligand-modified nanoparticulate liposomes having surfaces for binding to a specific receptor of a target cell. Applicant’s disclosure throughout the specification shows subjecting the nanoparticulate liposomes to ultrasonic irradiation as a mechanism of ultrasound stimulation under specific conditions to remove the protein corona on the nanoparticle surface to thereby restore and facilitate the nanoparticulate liposome ligand specific binding capacity.
The state of the prior art:
The prior art of record fails to disclose Applicant’s invention, as claimed. Claim 1 recites a method for removing protein corona of protein corona-modified nanometer particle which is a nanoparticle or liposome (claim 2). The method comprises subjecting the protein corona-modified nanometer particle to ultrasound stimulation to remove the protein corona from the protein corona-modified nanometer particle; wherein the nanometer particle comprises perfluoropentane. The ultrasound stimulation is performed under protein-containing or protein free condition (claim 3); and the protein-containing condition comprises blood, serum, plasma, and/or culture medium (claim 4) which comprises serum, plasma, and/or tissue protein-containing culture medium (claim 5).
The breadth of the claims:
The broad scope of the instant claims are directed to any nanometer particle or nanoparticle regardless of particle composition, particle source, nanoparticle surface protein corona modification and conditions, and ultrasound stimulation.
The predictability or lack thereof in the art:
There is no predictability based on Applicant’s disclosure in the instant specification that the claimed method will work in all nanometer particle compositions or nanoparticles under generic undefined ultrasound stimulation conditions.
The amount of direction or guidance present:
Applicant’s disclosure throughout the specification provides the nanometer material as a lipid material of a liposome that encapsulates perfluoropentane prepared by the method disclosed in paragraphs [0017] to [0122]. This liposome is specifically LPGL or PGL in paragraphs [1353] to [1361] and paragraphs [1365-1367]. Appropriate guidance appears to be provided by the specification for a method to remove protein corona of protein corona modified nanoparticulate liposomes, limited specifically to protein corona modified LPGL using ultrasound stimulation having specifically defined acoustic intensity, frequency, duty cycle, and duration time parameters in paragraphs [0635] to [0637], Figures 4-6, and especially paragraph [1381] and Figure 4. However, the specification fails to provide guidance to enable the claimed method to remove protein corona on any protein corona modified nanoparticle using undefined ultrasound stimulation, as recited in claims 1-5.
The presence or absence of working examples:
The working examples are provided in the specification that show a method of removing corona protein modified LPGL liposomes prepared by Applicant’s disclosure in paragraphs [1365] to [1367] using ultrasound stimulation limited to specifically defined acoustic intensity, frequency, duty cycle, and duration time parameters in paragraphs [1379] to [1381] and Figure 4. There are no working examples that show analogous results in other protein corona modified nanometer particles using undefined generic ultrasound stimulation, which are encompassed by the broad scope of the instant claims.
The quantity of experimentation necessary:
For all the reasons aforementioned, it would require undue amount of experimentation for the skilled artisan to make, use, and/or practice the method, as claimed.
The claimed invention must bear a reasonable correlation with enablement of the claimed method. In re Fisher, 166 USPQ 18(CCPA 1970) indicates that the more unpredictable an area is, the more specific enablement is necessary in order to satisfy the statute. In view of the quantity of experimentation necessary, the unpredictability of the art, the lack of sufficient guidance in the specification, the limited working examples, and the limited amount of direction provided given the breadth of the claims, it would take undue experimentation to practice the claimed invention.
5. Claims 1-5 are free of the prior art of record.
6. No claims are allowed.
Remarks
7. Prior art made of record are not relied upon but considered pertinent to the applicants' disclosure:
Jonathan Shannahan. (The biocorona: a challenge for the biomedical application of nanoparticles. Nanotechnol Rev. 6 (4): 345-353 (August 2017)) teaches that to synthesize effective nanotherapeutics, it is necessary to elucidate interactions between the nanoparticle and the biological media that result to corona formation.
Adamson et al. (Experimental challenges regarding the in vitro investigation of the nanoparticle-biocorona in disease states. Toxicol In Vitro 51: 40-49 (September 2018)) evaluates the role of low-density lipoprotein (LDL) in altering macrophage responses to iron oxide NPs.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to GAILENE R. GABEL whose telephone number is (571)272-0820. The examiner can normally be reached Monday, Tuesday, and Thursday 5:30 AM to 4:00 PM.
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, Gregory S. Emch can be reached at (571) 272-8149. 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.
/GAILENE GABEL/Primary Examiner, Art Unit 1678
February 3, 2026