CTNF 18/000,258 CTNF 79815 DETAILED ACTION The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA. Per amendment dated Claims 1-17, 42-44, 58-60 are currently pending in the application. Applicant’s election without traverse of Group I invention, encompassing claims 1-16, 58-60) in the reply filed on 10/15/25 is acknowledged. Claims 17, 42-44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Specification The disclosure is objected to because the scope of compounds “polyethylene glycol methylethyl methacrylate (PEG-MEMA)” and “hydroxyethylmethyl methacrylate (HEMA)” recited in paragraphs [0023]-[0028] is unclear. Appropriate corrections and/or clarifications are required. Claim Objections Claims 1, 4, 6, 7, 9, and 16 are objected to because of the following informalities: In claims 1, 4, 6, 7, 9, and 16, terms “mixtures” and “combinations” appear synonymous. The claims may be amended to delete or the other to avoid redundancy. In claim 7, given that the species recited correspond to monomers (for providing the monomeric units), the claim language may be amended to clarify that the monomeric unit is derived from the recited monomers. Appropriate corrections and/or clarifications are required. Claim Rejections - 35 USC § 112 07-30-02 AIA 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. 07-34-01 Claims 1-8, 11-16, 58-60 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 7 recites “polyethylene glycol methylethyl methacrylate (PEG-MEMA)” and “hydroxyethylmethyl methacrylate (HEMA)” as species of the second monomeric unit. The claim is indefinite because the scope of the claimed compounds lack clarity. For the purpose of examination, polyethylene glycol methylethyl methacrylate (PEG-MEMA) and hydroxyethylmethyl methacrylate (HEMA) are interpreted as polyethylene glycol methyl ether methacrylate and hydroxyethyl methacrylate, respectively, based on art recognized acronyms “PEG-MEMA” and “HEMA”. The scope of claim 1 lacks clarity due to the recitation of “polyethylene glycol (PEG)” as a neutral group, in view of the disclosure. The disclosure recites polyethylene glycol methylethyl methacrylate (PEG-MEMA) (also recited in claim 7) as a monomeric unit that includes PEG moiety [0023]-[0028]. Incorporating the discussion on interpretation of (PEG-MEMA) from paragraph 7 above, it is unclear if “polyethylene glycol (PEG)” recited in claim 1 refers to a polyethylenoxy group, a hydroxyl-terminated polyethyleneoxy group or a methyl-terminated polyethyleneoxy group. For the purpose of examination, claim 1 interpreted as including any of these options. Claims 1-6, 8, 11-16, 58-60 are subsumed by this rejection because they depend on rejected base claim 1. Claim 16 is indefinite. A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 16 recites the broad recitations “RNA”, “DNA” and “protein”, and the claim also recites “such as single guide ribonucleic acid (sgRNA), messenger RNA (mRNA), or inhibitory RNA”, “such as plasmid DNA (pDNA) and “such as ribonucleic protein (RNP)”, which are the corresponding narrower statements of the range/limitation. The claim is considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Claim Rejections - 35 USC § 102 and 103 07-07-aia AIA 07-07 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 – 07-08-aia AIA (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. 07-20-aia AIA 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. 07-15 AIA Claim s 1-4, 6, 7, 14-16, 58 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Mallapragada et al. (US 6,998,456 B1) . Regarding claims 1, 2, 4, 6, 7, 16, 58, Mallapragada teaches cationic pH sensitive methacrylic copolymers constructed from tertiary amine methacrylates and poly(ethylene glycol) containing methacrylates, such as copolymers of poly(ethylene glycol) methyl ether methacrylate (PEGMEM) and 2-(N,Ndiethylaminoethyl) methacrylate (DEAEM), for associating with proteins and pharmaceuticals for drug delivery or protein separation (Ab., col. 2, lines 50-67, col. 3, lines 45-col. 7, line 28, Fig., Examples, reference claims). Regarding claim 3, per instant disclosure (PGPUB - [0081]), pKa of 2-(N,Ndiethylaminoethyl) methacrylate is 8.14. Regarding claims 14 and 15, given that the disclosed copolymers include monomer units within the scope of the claimed invention, and given that amino acids are the building blocks of proteins, an acid group therein must inherently be capable of interacting with a cationic group of the copolymer via electrostatic attraction and/or cause the protein to be entangled within the copolymer. In light of above, presently cited claims are anticipated by the reference . 07-21-aia AIA Claim s 14, 15, 59 and 60, are rejected under 35 U.S.C. 103 as being unpatentable over Mallapragada et al. (US 6,998,456 B1) . The discussion on Mallapragada from paragraphs 13-15 above is incorporated herein by reference. Mallapragada further teaches a range of 1-5000 units of each monomer in the copolymer, wherein a monomer (I) unit shown below may have an amine group NR 6 R 7 as Z, wherein R 3 , R 6 and R 7 may be C 1 -C 6 alkyl: PNG media_image1.png 278 130 media_image1.png Greyscale The reference teaches that the copolymers are pH sensitive and control the release of associated materials, such as proteins, based on the pH of the surrounding environment (col. 2, line 30-col. 3, line 9). Mallapragada is silent on the biological agent being entangled or bound as claimed (claims 14,15), or a pK a or a Hill coefficient of the copolymer as in the claimed invention (claims 59, 60). At the outset, it is noted that in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. See MPEP § 2144.05. Regarding claims 14 and 15, as an alternative to the anticipation rejection, given the teaching on copolymers comprising monomeric units within the scope of the claimed invention for associating with proteins, and given that amino acids are the building blocks of proteins, it would have been obvious to one of ordinary skill in the art, as of the effective filing date of the claimed invention, to reasonably expect the acid functionality in proteins and the cationic groups of the copolymer to interact via electrostatic attraction and/or to cause the protein to be entangled within the copolymer, absent evidence to the contrary. Regarding claims 59 and 60, given the teaching on pH-sensitive copolymers that have a broad range of 1-5000 monomers units that fall within the scope of the claimed monomeric units, it would have been obvious to one of ordinary skill in the art to prepare copolymers within the scope of Mallapragada, and reasonably expect the copolymers of overlapping scope to have the claimed pKa or Hill coefficient, absent evidence to the contrary. As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons. In re Brown , 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972) . 07-15 AIA Claim s 1-8, 11 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Peng et al. (NPL document # 76 cited in and submitted with the IDS dated 12/20/23) . Regarding claims 1, 2, 4-8, Peng teaches a pH sensitive self-assembled block/statistical copolymer poly(poly(ethylene glycol)methyl ether methacrylate) - b-poly(2-(diisopropylamino) ethyl methacrylate-co-2-hydroxyethyl methacrylate)- chlorin e6 as a theranostic antimicrobial agent (Ab., Scheme 1, Introduction, Experimental section, Figures 1-8, Table 1 and Results and Discussion). Disclosed chlorin e6 reads on a biological agent. Regarding claim 3, Peng teaches a copolymer comprising units of (2-diisopropylamino) ethyl methacrylate (DIPAEMA). It is noted that per instant disclosure (PGPUB-[0081]), DIPAEMA has a pK a of 8.38. Regarding claim 11, the calculated M w of Peng’s poly(poly(ethylene glycol)methyl ether methacrylate) - b-poly(2-(diisopropylamino) ethyl methacrylate-co-2-hydroxyethyl methacrylate) (PPEGMA-b-P(DPA-co-HEMA) from the disclosed M n (GPC) and polydispersity values falls within the claimed range (Fig. 1, Table 1). In light of above, the presently cited claims are anticipated by the reference . 07-21-aia AIA Claim s 12, 13, 59 and 60 are rejected under 35 U.S.C. 103 as being unpatentable over Peng et al. (NPL document # 76 cited in and submitted with the IDS dated 12/20/23) The discussion on Peng from paragraphs 23-25 is incorporated herein by reference. Peng is silent with regard to the pKa or a zeta potential as claimed (claims 12, 13, 59) or a Hill coefficient as recited in claim 60. Peng teaches a copolymer (Experimental Section 2.2.3) comprising units within the scope of instant claims 1 and 8. It would have been obvious to one of ordinary skill in the art, as of the effective filing date of the claimed invention, to prepare copolymers within the scope of Peng and reasonably expect the same to have a pKa, zeta potential or Hill coefficient within the claimed ranges, absent evidence to the contrary. As stated in paragraph 21 above, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons . 07-15 AIA Claim s 1, 2, 7, 16, 58 are rejected under 35 U.S.C. 102( a)(1 ) as being anticipated by Esselin et al. (WO2016/005693 A1, machine translation) . Esselin teaches statistical cationic copolymers comprising between 30 and 75 % (m/m) 28 dimethylaminopropyl methacrylamide (DMAPMA) monomers or their derivatives, between 10 and 45 % (m/m) hydroxyethyl methacrylate (HEMA) its derivatives, and between 10 and 50 % (m/m) aminoethyl methacrylate (AEMA) monomers or their derivatives (Ab.). Disclosed preferred embodiment is drawn to a cationic random copolymer comprising 33 wt.% dimethylaminopropyl methacrylamide monomers (DMAPMA), 33 wt.% hydroxyethyl methacrylate (HEMA) and 33 wt.% aminoethyl methacrylate monomers (AEMA) (Fig. 3, 5, line 332, lines 455-459, lines 651-665). Additionally, disclosed ingredients that can be encapsulated by the random cationic copolymers include pharmacologically active molecules, amino acids, peptides, proteins etc. lines 683-699). Although Esselin discloses a genus of ingredients for encapsulation that include biological agents, Applicant’s attention is drawn to MPEP 2131.02 (A) which states that “...when the species is clearly named, the species claim is anticipated no matter how many other species are additionally named”. Ex Parte A , 17 USPQ2d 1716 (BPAI, 1990). In light of above, the presently cited claims are anticipated by the reference . Allowable Subject Matter 12-151-08 AIA 07-43 12-51-08 Claim s 9 and 10 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Conclusion 07-96 AIA The prior art made of record and not relied upon is considered pertinent to applicant's disclosure : Venkatraman et al. (NPL citation # 101) and Zhao et al (NPL citation # 119) (references cited in the IDS dated 12/20/23) . Venkataraman teaches cationic copolymers formed from 2-(dimethylamino)ethyl methacrylate and poly(ethylene glycol) methyl ether methacrylate P(DMAEMA-co-OEGMA) that may be effectively complexed with DNA. Zhao teaches plasmid DNA complexation with diblock copolymers of 2-methacryloxyethyl phosphorylcholine) and 2-(methylamino)ethyl methacrylate. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Satya Sastri at (571) 272 1112. The examiner can be reached Monday-Friday, 9AM-5.30PM (EST). If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Mr. Robert Jones can be reached at (571)-270- 7733. The fax phone number for the organization where this application or proceeding is assigned is (571) 273 8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll- free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272- 1000. /Satya B Sastri/ Primary Examiner, Art Unit 1762 Application/Control Number: 18/000,258 Page 2 Art Unit: 1762 Application/Control Number: 18/000,258 Page 3 Art Unit: 1762 Application/Control Number: 18/000,258 Page 4 Art Unit: 1762 Application/Control Number: 18/000,258 Page 5 Art Unit: 1762 Application/Control Number: 18/000,258 Page 6 Art Unit: 1762 Application/Control Number: 18/000,258 Page 7 Art Unit: 1762 Application/Control Number: 18/000,258 Page 8 Art Unit: 1762 Application/Control Number: 18/000,258 Page 9 Art Unit: 1762 Application/Control Number: 18/000,258 Page 10 Art Unit: 1762