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 .
Status of Claims
Amendment filed on 11/13/2025 is acknowledged.
Claims 29-32, 34-37, and 50 remain withdrawn without traverse on 06/18/2025 for being drawn to nonelected group. Claims 6, 8-11, 13, 16-17, 21-22, 24-25, 27-28, 33, 38-49, 51-66 remain cancelled.
Claims 1, 5, 7, 14, and 18 are amended.
Claims 1-5, 7, 12, 14-15, 18-20, 23, and 26 are pending and being examined on merits herein.
Priority
This instant application 18012048, filed on 12/21/2022, is a 371 PCT/US2021038449, filed on 06/22/2021, which claims benefit of 63042386, filed on 06/22/2020, and also claims benefit of 63210222, filed on 06/14/2021.
Withdrawn Objections/Rejections
All previous claim Objection(s) / Rejection(s) as set forth in the previous Office action (mailed 07/14/2025) that are not repeated and/or maintained in the instant Office action are withdrawn, in light of applicant’s amendment and remark filed on 11/13/2025.
Maintained and New Objections/Rejections
The following are maintained and new objections/rejections.
Claim Objection
Claims 7 and 20 are objected to because of the following informalities:
Claim 7 recites “, or an antimicrobial fragment of any of”. The word “or” should be removed, since only the last alternative at the end of the claim requires “or”.
Claim 20 recites “(HEMA diethylacrylamide,” the parentheses have to be a pair.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-5, 7, 12, 14-15, 18-20, 23, and 26 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 “environment-sensitive (co)polymer” in line 7. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “environment” in claim 1 is used by the claim to mean “ the aqueous environment in which the particle are suspended, and not the external-environment of an organism or vessel in which the aqueous solution comprising the polymer is contained.” The term is indefinite because the specification description is confusing and it does not clearly redefine the term. The spec expresses that the environment is meant to be the “aqueous environment, …not the external-environment”, however, the aqueous environment containing the polymer is in the external environment based on the language, and then logically the aqueous environment should be part of the external environment. The term is indefinite because the specification does not clearly redefine the term, plus, there is no aqueous environment mentioned in instant claim 1 scope. Instant specification goes on further to explain the term, but fails to clarify the aqueous environment is not the external environment, rather, it makes it appear the external environment provides significance and influence on the polymer, indicating that external environment can affect the aqueous environment and lead to “changing at least one aspect of the block copolymers”. But, without describing aspects of the (co)polymer in claim, other than its attachment order in the polymer chain, what environmental factors can lead to aspect change of the block copolymer also fails to establish a definite meaning regarding “environment-sensitive (co)polymer”. Therefore, the “environment-sensitive (co)polymer” renders the claim indefinite.
Claims 2-5, 7, 12, 14-15, 18-20, 23, and 26 are rejected accordingly because they are directly or indirectly depending on claim 1 without further clarifying the issue in claim 1 as addressed above.
Claim 7 recites “any of the preceding”. It is unclear what contents are included in “any of the preceding”, now that there are only “crystal violet, a polyamine plant growth promoter” are remained and both do not appear to contain antimicrobial “fragment” based on the names.
Claim Interpretation
Claims 1, 7 and 23 are interpreted as following.
Claim 1 is interpreted as a composition comprising a star, comb, bottlebrush, or dendritic polymer particle having a diameter of 50 nm or less, the particle comprising:
a core moiety; and
pendent block copolymer chains extending from the core moiety, comprising
a first acidic or basic (co)polymer segment attached to and extending from the core, and
a second (co)polymer segment attached to and extending from the first segment,
wherein the first segment, and the second segment each, independently, have a polydispersity index of no more than 2, and the second (co)polymer is environmental sensitive. The term environmental sensitive is interpreted under BRI as responsive to any environmental conditions including but not limited to, temperature, pH, humidity, light, etc.
Claim 7 is interpreted as the composition of claim 3, wherein the cargo is crystal violet, a polyamine plant growth promoter, an antimicrobial fragment, or an antimicrobial synthetic peptide.
Claim 23 phrase of “the second segment oxidizes in the presence of a reactive oxygen species (ROS), becoming more soluble in an aqueous solution” is interpreted as the property of second segment. Regarding the second segment optionally comprises one or more pendant thioether, boronic ester, or selenium-containing groups, or one or more 2-(Methylthio)ethyl acrylate residues, because they are optional, therefore, they do not have to be in the segment structure.
Claim Rejections - 35 USC § 102
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 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 –
(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.
Claims 1-2, 15, 18-20 and 23 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Schilli et al. (Macromolecules, 07/23/2004, 37, 7861-7866, PTO-892).
Schilli throughout the reference teaches a composition of double-responsive block copolymer synthesized via RAFT polymerization: poly(N-isopropylacrylamide)-block-poly(acrylic acid, PNIPAAm-b-PAA (e.g., Title, Abstract).
Regarding instant claim 1, Schilli teaches PNIPAAm-b-PAA block copolymer forms starlike micelles in aqueous solutions in dependence on pH and temperature (Pg. 7866, Conclusion), corresponding to star polymer particle in instant claim. Schilli teaches that PNIPAAm-b-PAA can form starlike particles or other aggregates depending on solvent, temperature, pH, and block lengths (Figure 1, Pg. 7681, right column top), showing that one part the block polymers, e.g., a part of acidic PAA, forming the core moiety, and the pendent block copolymer chains extending from the core moiety, the rest of the polymer segment attached to and extending from the core, and PNIPAAm segment attached to and extending from the first segment, corresponding to the copolymer segment arrangement in instant claim 1.
Schilli teaches the radius of particles with the unimer peak being dominant indicating the particle radius at around 20 nm within 20 C to 35 C temperature range (Pg. 7863, right column, 2nd paragraph), falling within the particle diameter range of 50 nm or less as in instant claim 1. MPEP 2131.03.I states that "If the prior art discloses a point within the claimed range, the prior art anticipates the claim." UCB, Inc. v. Actavis Labs. UT, Inc., 65 F.4th 679, 687, 2023 USPQ2d 448 (Fed. Cir. 2023).
Schilli teaches that PNIPAAm, which can be the second segment as shown in Fig. 1, is thermoreponsive and polyarylic acid is pH responsive (Pg. 7863, Left Column, 3rd paragraph), corresponding to second segment, e.g., PNIPAAm, is environment-sensitive segment. PNIPAAm-b-PAA block copolymer with a PAA block length equal to 110 monomer units and NIPAAm block length of n units show very low polydispersity index of both segments independently, mostly lower than 2 (Table 1, Pg. 7862; Results and Discussion, Pg. 7862, right column), corresponding to polydispersity index in instant claim 1.
Regarding instant claim 2, Schilli teaches PNIPAAm-b-PAA is acidic and pH dependent.
Regarding instant claim 15, Schilli teaches PNIPAAm-b-PAA with PAA block length equal to 110 monomer units (Results and Discussion, Pg. 7862, right column), falling within the range and from 25 to 150 monomer residues in instant claim, and the instantly claimed range is therefore anticipated.
Regarding instant claim 18, Schilli teaches (NIPAAm)n-b-(AA)110 with PNIPAA units at 50, 54, 74, etc. and PAA as 110 monomers (Table 1, Pg. 7862; Results and Discussion, Pg. 7862, right column, last 2nd paragraph), resulting in ratio of first segment to second segment monomers at lowest as 50 : 110 (about 1 : 2.2 ), falling within the range from 1 : 1 to 1 : 7 as recited in instant claim 18, and therefore, the instantly claimed range is anticipated.
Regarding instant claim 19, Schilli teaches the segment NIPAAm, which can be the second segment in the star block polymer, is thermoresponsive (Pg. 7863, Left Column, 3rd paragraph).
Regarding instant claim 20, Schilli teaches PNIPAAm, has lower critical solution temperature (LCST) behavior in aqueous solutions, and a sharp phase transition is observed at 32 C in water (Introduction, Pg. 7861, 1st paragraph), falling within the instantly claimed range 25 C to 40 C, therefore, the claim is anticipated.
Regarding instant claim 23, in light of the claim interpretation as presented above, NIPAAm in prior art is the same second segment as evidenced by instant specification, and therefore, the property that NIPAAm oxidizes in the presence of ROS and becomes more soluble in an aqueous solution is inherent property of the segment.
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 1-2, 12, 14-15, 18-20 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Schilli et al. (Macromolecules, 07/23/2004, 37, 7861-7866, PTO-892), as applied to Claims 1-2, 15, 18-20 and 23 above, in view of Pang et al. (Macromolecules 09/02/2011, 44:7176-7183, IDS of 09/11/2023).
Schilli teaches a composition of PNIPAAm-b-PAA block copolymer that can form starlike particles having a diameter about 20 nm, and the particle comprising a core moiety, e.g., part of PAA, the pendent block copolymer chains extending from the core moiety and comprising first acidic segment PAA, and second thermosensitive segment, PNIPAAm, attached to and extending from the first segment, wherein the pendent chains, the first segment, and second segment each independently, have a polydispersity index of no more than 2, as applied to claims 1-2, 15, 18-20 and 23 above in great detail and incorporated herein.
Schilli does not teach the start block copolymer core is a polysaccharide residue as recited in instant claim 12, and the core is cyclodextrin as recited in instant claim 14.
Pang throughout the reference teaches starlike diblock copolymers (e.g., Abstract).
Pang describes starlike block copolymers polyacrylic acid-poly(3-hexylthiophene) (PAA-b-P3HT), based on a β-cyclodextrin (as a polysaccharide, corresponding to instant claims 12 and 14)-containing PAA core (Image, Abstract), forming unimolecular micelles wherein the acidic poly(acrylic acid) is directly attached to cyclodextrin and formed the core (e.g., Abstract). The polydispersity of polymers is about 1.1-1.2 (Table 1) and the hydrodynamic diameter of the unimolecular micelles is about 20 nm (page 7181, left column, 3rd paragraph).
It would have been prima facie obvious for a person with ordinary skills in the art prior to filing date to integrate the cyclodextrin into the star block polymer taught by Schilli to arrive at current invention. Because Schilli teaches that the PNIPAAm-b-PAA with temperature- or pH-sensitive micelles could eventually be used to confer bioadhesive properties, and pH sensitive micelles might be applied in drug delivery to endosomal compartments, it would be advantageous to keep the double responsive segment pendant chains for the star polymer, while Pang demonstrates that the star polymer with cyclodextrin core shares similar features, e.g., particle diameter and polydispersity index, moreover, using cyclodextrin as core initiation site facilitates the starlike polymer formation, as Pang specifies that cyclodextrin is a cyclic oligosaccharide consisting of seven glucose units linked by α-1,4-glucosidic bonds and the 21 substitutable hydroxyl groups on the outer surface of cyclodextrin offer the capability of generating a core with 21 initiation sites to form 21-arm, starlike block copolymers (Pg. 7177, left column, 2nd paragraph). This would have provided scientists in the field motivation to implement cyclodextrin core into the star polymer taught by Schilli for facilitated star formation. This renders obviousness as “use of known technique to improve similar devices (methods, or products) in the same way” or as “applying a known technique to a known device (method, or product) ready for improvement to yield predictable results”. See MPEP §2143. (I)(C) and (I)(D). Moreover, It is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (MPEP §2144.07). See Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
Claims 1-5, 15, 18-20, 23 and 26 are rejected under 35 U.S.C. 103 as being unpatentable over Schilli et al. (Macromolecules, 07/23/2004, 37, 7861-7866, PTO-892), as applied to Claims 1-2, 15, 18-20 and 23 above, in view of Niu et al. (C. R. Chimie 6, 2003, 1049-1059, PTO-892).
Schilli teaches a composition of PNIPAAm-b-PAA block copolymer that can form starlike particles having a diameter about 20 nm, and the particle comprising a core moiety, e.g., part of PAA, the pendent block copolymer chains extending from the core moiety and comprising first acidic segment PAA, and second thermosensitive segment, PNIPAAm, attached to and extending from the first segment, wherein the pendent chains, the first segment, and second segment each independently, have a polydispersity index of no more than 2, as applied to claims 1-2, 15, 18-20 and 23 above in great detail and incorporated herein.
Schilli does not teach the composition of star polymer PNIPAAm-b-PAA further comprising a cargo retained within the particle as recited in instant claim 3, the cargo is monoatomic, a non-peptidyl compound, or an antimicrobial peptide as recited in instant claim 4, the cargo comprises comprises i) Mg2+, Fe2+/Fe3+, and Zn2+, or ii) Ca2+, K+, Cu2+, Mn2+/or Mn4+, and Mo2+/ Mo6+, or iii) Ni2+ as recited in instant claim 5, or the composition further comprising a surfactant as recited in instant claim 26.
Niu throughout the reference teaches dendrimer-encapsulated metal nanoparticles (DEMNs) (e.g., Abstract).
Niu teaches that dendrimer/metal-ion composite materials, which are the precursors for DEMNs, are prepared by mixing solutions containing dendrimers and metal ions, such as Pt2+, Pd2+, Au3+, Ag+, Cu2+, Ni2+, Ru3+, Mn2+, and Fe3+ (Pg. 1050, right column, bottom), the metal ions are sorbed into the interior of dendrimers (corresponding to cargo retained within polymer particle in instant claim 3, cargo as monoatomic or non-peptidyl compound as in instant claim 4, and ions in instant claim 5). Niu teaches that after DEMNs being extracted from water into toluene as monodisperse inverse micelles by a surfactant, Pd nanoparticles encapsulated within fourth generation, amine-terminated PAMAM dendrimers exhibited better hydrogenation activity for allyl alcohol than water, which suggesting relatively hydrophilic interior of the PAMAM dendrimer molecule may facilitate partitioning of the substrate into the vicinity of the encapsulated nanoparticle (Pg. 1054, left column, bottom), corresponding to surfactant in instant claim 26.
It would have been prima facie obvious for a person with ordinary skills in the art prior to filing date to implement the cargo and surfactant taught by Niu into the star polymer particles in Schilli to arrive at current invention. Because Schilli specifies that star polymer particles can be used for drug delivery to endosomal compartments, sharing intended use for loading cargo in dendrimers as nanoparticles, since dendrimers and star polymers both have extending chains from the core, it would have motivated scientists to implement the same cargo taught by Niu, especially because Niu specifies that loading these metal ions subsequently chemically reduced to yield nearly size-monodisperse, zero-valent metal particles and that these composites serve not only as a template for preparing the nanoparticle replica, but they also stabilize the nanoparticle, make it possible to tune solubility, and enhance catalytic selectivity, and these materials have been used for a broad range of catalytic reactions, including hydrogenations, Heck coupling, and Suzuki reactions, in water, organic solvents, biphasic fluorous/ organic solvents, and supercritical CO2 (e.g., Abstract). Similarly, using surfactant in the composition appears to facilitate metal encapsulation, which would have motivated scientists to explore the substance for achieving the benefit. This renders obviousness as “use of known technique to improve similar devices (methods, or products) in the same way” or as “applying a known technique to a known device (method, or product) ready for improvement to yield predictable results”. See MPEP §2143. (I)(C) and (I)(D). Moreover, It is prima facie obvious to select a known material for incorporation into a composition, based on its recognized suitability for its intended use (MPEP §2144.07). See Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945).
Claims 1-5, 7, 15, 18-20 and 23 are rejected under 35 U.S.C. 103 as being unpatentable over Schilli et al. (Macromolecules, 07/23/2004, 37, 7861-7866, PTO-892) and Niu et al. (C. R. Chimie 6, 2003, 1049-1059, PTO-892) as applied to Claims 1-5, 15, 18-20, 23 and 26 above, further in view of Dimitrov (Prog. Polym. Sci. 32 (2007) 1275-1343, PTO-892).
Schilli teaches composition of PNIPAAm-b-PAA block copolymer that can form starlike particles having a diameter about 20 nm, and the particle comprising a core moiety, e.g., part of PAA, the pendent block copolymer chains extending from the core moiety and comprising first acidic segment PAA, and second thermosensitive segment, PNIPAAm, attached to and extending from the first segment, wherein the pendent chains, the first segment, and second segment each independently, have a polydispersity index of no more than 2, as applied to claims 1-2, 15, 18-20 and 23 above in great detail and incorporated herein. Niu teaches that dendrimer particles can retain metal ions as cargo within the particles.
Schilli and Niu do not teach the cargo is crystal violet, a polyamine plant growth promoter, an antimicrobial fragment, or an antimicrobial synthetic peptide as recited in instant claim 7.
Dimitrove teaches thermosensitive water-soluble copolymers with doubly responsive reversibly interacting entities having remarkable phase behavior capable of self-assembly into micelles and vesicles in aqueous solutions (e.g., Abstract). Dimitrov teaches telechelic polyoxazolines with antimicrobial dodecylammonium group (corresponding to antimicrobial fragment in instant claim 7), making stable star-shaped polyoxazolines with a polyhedral oligomeric silsesquioxane POSS core (Pg. 1289, left columm, 3rd-4th paragraph).
It would have been prima facie obvious for a person with ordinary skills in the art prior to filing date to implement the antimicrobial cargo taught by Dimitrove into the polymer particles in Schilli and Niu to arrive at current invention. Since all prior art teach that star polymer or dendrimers can be used as cargo carriers for drug delivery, while antimicrobial drug is one of the most commonly used drugs, choosing antimicrobial drug as a cargo flows naturally based on the teachings of Schilli and Niu, while Dimitrove teaches that the antimicrobial fragment, e.g., dodeclammonium group, can be the cargo in the core in the copolymerization that is terminated with acrylic acid (Pg. 1289, right column, top paragraphs), it would motivate scientists in the field to explore the antimicrobial fragment to be incorporated into the PAA-containing polymer as a cargo for antimicrobial benefits. This renders obviousness as combining prior art elements according to known methods to yield predictable results, see In Supreme Court KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 415-421, 82 USPQ2d 1385, 1395-97 (2007).
Response to Arguments
Applicant’s arguments/remarks filed on 11/13/2025 have been fully considered.
35 USC 112 b
Applicants assert that the rejection under 35 USC 112 b should be traversed by stating a definition for the term “environment sensitive” is provided.
The argument is not persuasive, because the definition of “environment sensitive” in specification is very confusing, as presented in the office action and explained in detail.
35 USC 102
Applicant’s arguments are moot because of new grounds of rejections as presented in this office action. Please refer to the entire office action as a complete response to remarks/arguments.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DONGXIU ZHANG SPIERING whose telephone number is (703)756-4796. The examiner can normally be reached 7:30am-5:00pm (Except for Fridays).
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/DX.Z./ Examiner, Art Unit 1616
/SUE X LIU/ Supervisory Patent Examiner, Art Unit 1616