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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 23 March 2026 has been entered.
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 23 March 2026.
CLAIMS UNDER EXAMINATION
Claims 1-5, 7-9 and 20 have been examined on their merits.
PRIORITY
The earliest claims to priority are Applications GB1916390.6 and GB1916388.0 filed on 11 November 2019.
WITHDRAWN REJECTIONS
The previous rejections have been withdrawn due to claim amendment.
NEW REJECTIONS
New grounds of rejection have been necessitated by claim amendment.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-3, 5, 7-9 and 20 are rejected under 35 U.S.C. 103 as being unpatentable Jiang et al. (previously cited; Particles coated with zwitterionic polymers comprising sulfobetaine or carboxybetaine. US20140235803A1) in view of Ranjan et al. (Synthesis of High Density Polymer Brushes on Nanoparticles by Combined RAFT Polymerization and Click Chemistry. Macromol. Rapid Commun. 2008, 29, 1104–1110) and Higaki et al. (Anti-fouling behavior of polymer brush immobilized surfaces. Polymer Journal (2016) 48, 325–331) as evidenced by Cardenes et al. ALCAM/CD166IsInvolved in the Binding and Uptake of Cancer-Derived Extracellular Vesicles. Int. J. Mol. Sci. 2022).
Jiang et al. teach particles grafted with zwitterionic polymers (Abstract). The art teaches Reversible addition fragmentation chain transfer (RAFT) polymerization can be used to prepare the particles ([0116]). As evidenced by the instant specification “the coated particles can be prepared by growing a zwitterionic polymer from the surface of a particle using …RAFT polymerization (page 15, lines 27-31). Because Jiang teaches RAFT, it would grow the polymer on the surface of the particle as claimed.
The surface of the particle can comprise a target binding partner coupled to a portion of the plurality of polymers adhered to the surface ([0135]). A binding pair member can be any suitable molecule including a protein ([0137]). The art identifies “antibodies (monoclonal, polyclonal, chimeric, single-chain or other recombinant forms)” as proteins that can be immobilized on the surfaces of disclosed particles ([0138]). The art discloses anti-ALCAM as a model antibody ([0166]). As evidenced by Cardenes et al., ALCAM/CD166 is involved in the binding and uptake of cancer derived extracellular vesicles, including exosomes (see page 2, third paragraph; page 6, last paragraph; see page 16, section 4.7). Therefore the antibody has an affinity for a population of exosomes.
Jiang teaches particles having zwitterionic polymers on their surfaces impart low fouling properties to the particles ([0092]). The art teaches the surface of the invention the surface of the invention specifically binds to the cell and resists non-specific protein adsorption and non-specific cell adhesion ([0140]).
Jiang teaches particles having zwitterionic polymers on their surfaces impart low fouling properties to the particles. Jiang is silent regarding the amount of polymer covering the particle surface.
Ranjan teaches a method of making high density polymer brushes on nanoparticles (hence, particles) using RAFT (Abstract; see page 1105, left column, first paragraph). The art teaches a surface grafting density of 1.2-1.3 groups /nm2 (page 1108, left column, second paragraph).
The following is also taught by Ranjan:
The art teaches the selection of RAFT chain transfer agent (CTA) is crucial to synthesizing well-defined polymer brushes. This approach affords higher molecular weight and grafting density of the attached polymer. The more reactive trithiocarbonate type RAFT CTA is used to further increase the grafting density. (See page 1106, left column, second paragraph). For a high grafting density of the polymer it is important to introduce RAFT CTA on the surface with a high grafting density (page 1108, right column, first paragraph). The art teaches immobilizing the reactive CTA in order to achieve better efficiency (same cited section).
Higaki teaches zwitterionic polyelectrolyte-tethered surfaces represent significant anti-fouling materials for bio-macromolecules (Abstract). The art teaches exposure of material interfaces to foreign substances and foulants impacts performance (see page 325, left column, first paragraph). Higaki teaches a polymer brush is a surface tethered polymer layer (page 326, left column, first paragraph of “Anti-Fouling Characteristics of Polymer Brushes”). The art teaches formation of high density polymer brushes (same cited section).
It would have been obvious to cover at least 80% of Jiang’s particle with polymer. Jiang teaches RAFT polymerization and Ranjan teaches optimizing the conditions of RAFT polymerization to produce high density polymer brushes on a particle surface. Ranjan teaches the type of chain transfer agent, and amount of CTA grafted to the surface affect the density (amount) of polymer on the particle surface. The skilled artisan would optimize RAFT conditions to obtain a particle with the desired amount of polymer. One would have been motivated to cover at least 80% with high density polymer brushes since Jiang teaches particles with low fouling properties Higaki teaches polymer brushes confer anti-fouling properties. One would do so to ensure the entire particle has antifouling properties, avoiding non-specific absorption. One would have had a reasonable expectation of success since Jiang teaches RAFT can be used to prepare the disclosed particles. Therefore claim 1 is rendered obvious.
Jiang teaches carboxybetaine and sulfobetaine polymers ([0132]). Therefore claim 2 is rendered obvious. Jiang teaches Zwitterionic Poly(Carboxybetaine) ([0312]). Therefore claim 3 is included in this rejection.
Jiang teaches particles with an average diameter of 58.4 nm ([0157]). Therefore claim 5 is included in this rejection.
Jiang teaches a coating thickness was around 20 nm ([0157]). Therefore claim 7 is included in this rejection.
Jiang teaches the surface of the invention specifically binds to the cell and resists non-specific protein adsorption and non-specific cell adhesion (supra). Jiang teaches the particles have low fouling properties ([0089]). polymers with ultra-low fouling ([0058][0181] [0222]). Because the claimed particle is rendered obvious, it would be expected to have a nonspecific adsorption of less than 10%. Therefore claim 8 is included in this rejection.
Ranjan and Higaki teach polymer brushes (supra). Therefore claim 9 is included in this rejection.
Claim 20 recites a product by process method. See MPEP 2113. Claim 1 is directed to a product. The method recited in claim 20 does not distinguish the claimed particle from the particle rendered obvious by the prior art. Therefore claim 20 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious.
Claim 4 is rejected under 35 U.S.C. 103 as being unpatentable over Jiang in view of Ranjan and Higaki as applied to claim 1 above, and further in view of Zhang et al. (previously cited; Method for enriching CNS-derived exosomes. US20170102397A1).
Claim 1 is rejected on the grounds set forth above. The teachings of Jiang and Higaki are reiterated. Jiang teaches the particle surface may comprise a target binding partner with an affinity toward a target molecule. In these embodiments, the surfaces can be used in diagnostic assays ([0135]).Jiang teaches a particle functionalized with an antibody. The art is silent regarding an anti-L1CAM antibody.
Zhang teaches a method for enriching CNS-derived exosomes (Abstract). Zhang uses an anti-L1CAM antibody (see claim 1 of Zhang; [0018]). The art teaches L1CAM is a neuronal cell adhesion molecule ([0015]). Zhang teaches anti-L1CAM can be indirectly immobilized on a solid phase ([0022]). Zhang teaches the use of bads (particles) ([0035]). The art teaches diagnosis of a neurological disease using an anti-L1CAM antibody ([0030]).
It would have bene obvious to prepare a particle comprising an anti-L1CAM antibody. Jiang teaches functionalizing a particle with an antibody for disease diagnosis and Zhang teaches functionalizing a solid phase with anti-L1CAM for disease diagnosis. One would use anti-L1CAM to diagnose a neurological disorder, as taught by Zhang. One would have had a reasonable expectation of success since Zhang teaches particles can be functionalized with anti-L1CAM. One would have expected similar results since both references are directed to particles functionalized with antibodies for diagnosis. Therefore claim 4 is included in this rejection.
Therefore Applicant’s Invention is rendered obvious,
RESPONSE TO APPLICANT’S ARGUMENTS
The arguments made in the response filed on 23 March 2026 are acknowledged.
The arguments directed to Yoshida and Wikberg are moot. New grounds of rejection have been made above.
Argument 1: The Applicant alleges Jiang teaches away from RAFT because it teaches other methods (e.g., ATRP) of polymerization.
Response to Argument 1: The Applicant elected the claims drawn to a product in the restriction election filed on 11 July 2025. While the Applicant’s arguments directed to the method of polymerization (RAFT), the claims are directed to a product. Claim 1 recites a particle coated with a zwitterionic polymer conjugated to a ligand with affinity for a population of exosomes, wherein at least 80% of the particle surface is coated with polymers. While the recitation “obtainable by RAFT” is acknowledged, the limitation is directed to a process and not a method. The patentability of a product does not depend on its method of production. See MPEP 2113. Jiang teaches a particle with a coating comprising a zwitterionic polymer coated to a ligand. Jang teaches an antibody which has an affinity for a population of exosomes. Jiang teaches RAFT can be used for polymerization. Disclosure of another method of polymerization is not a teaching away because Jiang teaches RAFT can be used. Therefore the arguments are not persuasive.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 270-8439.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
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