DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after 16 March 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Claims
Amendments to the Claims and Arguments/Remarks filed 20 April 2026, in response to the Office Correspondence dated 20 January 2026, are acknowledged.
The listing of Claims filed 20 April 2026, have been examined. Claims 1, 4-6, and 8-11 are pending. Claims 1 and 4 are amended, claims 2, 3, and 7 are canceled, and new claims 9-11 have been added.
Information Disclosure Statement
The Information Disclosure Statement, filed 4 February 2026, is acknowledged and has been considered.
Response to Amendment
The amendments have been entered and considered. The applicant amended independent claims 1 and 4 to incorporate Formula (I) and Formula (II), respectively, and canceled claims 2, 3, and 7. Regarding the prior rejections under 35 U.S.C. §112(b), the applicant removed the previously challenged phrase "crosslinking block portion positioned between the hydrophilic block and the cationic hydrophobic block" from claim 1. Accordingly, that ground of rejection is withdrawn as moot. Former claim 7 has been canceled. Accordingly, the prior §112(b) rejection directed to claim 7 is withdrawn as moot.
The applicant additionally amended claims 1 and 4 to recite a "cationic hydrophobic block that is more hydrophobic than the hydrophilic block portion." The prior rejection questioned whether simultaneous recitation of "cationic" and "hydrophobic" created an internal inconsistency. Upon reconsideration, the amendment clarifies that hydrophobicity is being defined comparatively relative to the hydrophilic block rather than as an absolute property. Amphiphilic and cationic polymer systems are known in the art. Accordingly, the prior rejection directed to the phrase "cationic hydrophobic block portion" is withdrawn. However, although the amendments overcome the prior grounds, new issues arise under 35 U.S.C. §112(b), as outlined below.
Regarding the prior rejections under 35 U.S.C. § 103, the applicant argues that amended claims 1 and 4 now include structural limitations not addressed in the prior rejection, particularly the recited Formula (I)/(II), L1, L2, and the amended architecture. Because the independent claims have materially changed, wherein claims 1 and 4 have been narrowed to specific Formula (I)/(II) structures and fixed substituent definitions (L¹ = divalent hydrocarbon; L² = single bond; m/n = 1-2, etc.), the prior 35 U.S.C. § 103 rejections are withdrawn and are superseded by new grounds of rejection under 35 U.S.C. § 103, as detailed below. Accordingly, the applicant’s Remarks are moot, in view of the filed amendments to the claims.
The prior art collectively teaches use of comparable conventional polymer linker structures and hydrazone-containing polymer architectures, as detailed below. Accordingly, the claimed subject matter as a whole would have been obvious to one of ordinary skill in the art at the time of invention.
New Rejections
The following new rejections are made from the previous Office Correspondence, dated 20 January 2026, as the applicant's amendment necessitated the new grounds of rejection presented below based on the amendments and newly cited limitations.
Claim Rejections - 35 USC § 112(b)
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 Applicant regards as his invention.
Claims 1, 4-6, and 8-11 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, regards as the invention.
Claims 1 and 4 recite "more hydrophobic than the hydrophilic block portion". The phrase "more hydrophobic" constitutes a term of degree. When a term of degree is used in a claim, the specification must provide some standard for measuring the scope of the term (see MPEP §2173.05(b)). Neither the claims or the specification establishes an objective standard for determining hydrophobicity or comparative hydrophobicity (e.g., the claims do not specify partition coefficient (logP/logD), contact angle, Hansen solubility parameters, water solubility, hydrophilic-lipophilic balance, or any other quantitative metric).
The specification likewise fails to identify a controlling methodology for determining whether one polymer block is "more hydrophobic" than another. Without objective boundaries, a person of ordinary skill in the art cannot determine with reasonable certainty whether a given polymer composition falls within or outside the scope of the claims (see Nautilus, Inc. v. Biosig Instruments, Inc., 572 U.S. 898, 910 (2014)). Dependent claims 5, 6, and 8-11 are included because they do not cure this defect. Appropriate correction is required.
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-AlA 35 U.S.C. § 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AlA) 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, 4-6, and 8-11 are rejected under 35 U.S.C. § 103 as being unpatentable over Breitenkamp et al. (WO2006107903A2; published 12 October 2006, hereinafter referred to as “Breitenkamp”) in view of Kataoka et al. (Block copolymer micelles for drug delivery: design, characterization and biological significance. Adv Drug Deliv Rev. 2001 Mar 23;47(1):113-31; hereinafter referred to as “Kataoka”), and in further in view of Xu et al. (Acid-labile poly(ethylene glycol) shell of hydrazone-containing biodegradable polymeric micelles, J Bioact Compat Polym 2018;33(2):119-33; hereinafter referred to as “Xu”), Ponta and Bae (PEG-poly(amino acid) block copolymer micelles for tunable drug release, Pharm Res. 2010;27(11):2330-42; hereinafter referred to as “Ponta”), and Lee et al. (pH-Dependent morphology and optical properties of lysine-derived molecular biodynamers, Mater. Chem. Front., 2020, 4, 905-909; published 27 Dec 2019; hereinafter referred to as “Lee”).
Breitenkamp teaches polymeric micelles comprising hydrophilic polymer blocks, poly(amino acid) blocks, and drug-loaded micellar cores (¶[0033]). Breitenkamp further teaches "Polymer micelles with cationically charged core-forming blocks are used to encapsulate biomolecules such as plasmid DNA and siRNA" (¶[0023]) and reversible hydrazone crosslink chemistry as, "...crosslinked to form pH-reversible hydrazone crosslinks" (¶[0296]). Breitenkamp also teaches micelle particle sizes of about 20–200 nm (¶[0022]).
Kataoka teaches poly-ion complex (PIC) micelles comprising PEG-poly(amino acid) block copolymers wherein polylysine functions as a cationic segment for complexation of nucleic acids (page 120, Section 5). Kataoka additionally teaches "cross-linking by reversible bonds is a promising method" for controlled release and micelle destabilization (pages 126-127, section 9), micelle diameters of approximately 80-149 nm, and polydispersity values as low as 0.03-0.19 (page 123-126, section 7 and 8).
However, Breitenkamp and Kataoka do not expressly disclose the precise Formula (I) or Formula (II) structures recited in claims 1 and 4. Specifically, the references do not expressly teach the precise hydrazone-containing structural arrangement of Formula (I)/(II), the exact claimed L¹ and L² definitions, and explicit incorporation of hydrazone-containing repeating structures within the claimed block copolymer architecture.
Xu teaches hydrazone-containing block copolymers wherein hydrazone linkages are incorporated into polymer architecture between PEG and hydrophobic polymer segments for pH-responsive release (page 119, Abstract, and page 125, Figure 1). Xu further teaches pH-responsive destabilization and drug release resulting from hydrazone incorporation, as an approach for drugs not limited to doxorubicin (page 119, Abstract, and page 131, Conclusion).
Ponta teaches PEG-poly(amino acid) block copolymer systems suitable for micelle drug delivery and teaches amino-acid-derived polymer blocks suitable for controlling drug release characteristics and polymer functionality (page 2330, Abstract).
Lee further evidences incorporation of hydrazone-containing repeating units into lysine-derived polymer systems. Lee teaches lysine-derived dynamic polymer chains containing repeating acylhydrazone units integrated into polymer backbones. Lee demonstrates that hydrazone-containing repeating structures can be incorporated into lysine-derived polymer systems (page 905, Abstract and left column, and page 906, Fig.1).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date to modify the poly-ion complex micelles of Breitenkamp and Kataoka by incorporating hydrazone-containing polymer linkages as taught by Xu in order to impart environmentally responsive destabilization and controlled release characteristics. Kataoka expressly teaches that controlled destabilization and reversible crosslinking are desirable characteristics for polymeric micelle delivery systems (pages 126-127). Xu provides an identified solution for accomplishing the same objective through incorporation of hydrazone-containing polymer architecture. The substitution of one known element for another to obtain predictable results is ordinarily obvious (see KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007)).
Further, obviousness may be established by considering the combined teachings of references rather than bodily incorporation of one reference into another (see In re Keller, 642 F.2d 413, 425 (CCPA 1981)). One skilled in the art would further have been motivated to employ amino-acid-derived cationic blocks such as polylysine as taught by Kataoka because Breitenkamp expressly teaches encapsulation of anionic nucleic-acid therapeutics. Substituting one known core-forming polymer block with another known polymer block for the same intended purpose represents predictable use of prior-art elements according to their established functions (see KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398, 417 (2007)).
A reasonable expectation of success would have existed because all cited references concern polymeric drug-delivery systems, all involve self-assembling block copolymer systems, hydrazone chemistry was known as a pH-responsive design feature, and amino-acid-derived block modification represented a recognized design variable. Obviousness requires a reasonable expectation of success rather than absolute predictability (see In re O'Farrell, 853 F.2d 894, 903-04 (Fed. Cir. 1988)).
Regarding the instant dependent claims 5 and 9, Kataoka teaches polylysine-containing cationic polymer blocks suitable for complexation with nucleic acids (page 120). Regarding the instant dependent claims 6 and 10, Breitenkamp teaches micelles between 20-200 nm (¶[0022]). Kataoka teaches approximately 80-149 nm with PDI values as low as approximately 0.03-0.19. The claimed ranges overlap those disclosed in the art. A prima facie case of obviousness exists where claimed ranges overlap ranges disclosed in the prior art (see In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003)). Optimization of result-effective variables ordinarily involves routine skill (see In re Aller, 220 F.2d 454, 456 (CCPA 1955)). Regarding the instant dependent claims 8 and 11, Breitenkamp expressly teaches plasmid DNA and siRNA therapeutics (¶[0023]; claim 36). Selection of a known species from a disclosed class would have been obvious (see MPEP 2144.08).
Conclusion
No claims are allowed.
The applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). The applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (87 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to REBECCA L. SCOTLAND whose telephone number is (571) 272-2979. The examiner can normally be reached M-F 9:00 am to 5:00 pm EST.
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:/Awww.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’ s supervisor, Robert A. Wax can be reached at (571) 272-0623. 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:/Awww.uspto.gov/patents/apply/patent- center for more information about Patent Center and https:/Awww.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.
/RL Scotland/
Examiner, Art Unit 1615
/Jeffrey T. Palenik/Primary Examiner, Art Unit 1615
Prosecution Insights