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 .
Formal Matters
Applicants’ responses in the reply filed on 29 June 2026 are acknowledged and have been fully considered. Claims 1-20 are pending. Claims 1-4, 7, 9-12, and 15 are under consideration in the instant office action. Claims 5-6, 8, 14, and 16-20 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention and/or species, there being no allowable generic or linking claims.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 14 April 2025 is noted and the submissions follow the provisions of 37 CFR 1.97. Accordingly, the examiner has considered the references. A signed copy is attached herein.
Election/Restrictions
Applicant's election without traverse of Group I (claims 1-15) in the reply filed on 29 June 2026 is acknowledged. Additionally, Applicant’s election the species depicted below for examination in the reply filed on 26 May 2026 is also acknowledged.
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Claim Rejections - 35 USC § 102
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-4, 7, and 9-12 is/are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Hassler et al. (ACS Macro Lett. (2022) 11 (4): 460–467, IDS reference)
Applicants claim the below block copolymer:
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Hassler et al. disclose bottlebrush polymers are characterized by an expansive parameter space, including graft length and spacing along the backbone, and these features impact various structural and physical properties such as molecular diffusion and bulk viscosity. In this work, we report a synthetic strategy for making grafted block polymers with poly-(propylene oxide) and poly-(ethylene oxide) side chains, bottlebrush analogues of poloxamers. Combined anionic and sequential ring-opening metathesis polymerization yielded low dispersity polymers, at full conversion of the macromonomers, with control over graft length, graft end-groups, and overall molecular weight. A set of bottlebrush poloxamers (BBPs), with identical graft lengths and composition, was synthesized over a range of molecular weights. Dynamic light scattering and transmission electron microscopy were used to characterize micelle formation in aqueous buffer. The critical micelle concentration scales exponentially with overall molecular weight for both linear and bottlebrush poloxamers; however, the bottlebrush architecture shifts micelle formation to a much higher concentration at a comparable molecular weight. Consequently, BBPs can exist in solution as unimers at significantly higher molecular weights and concentrations than the linear analogues (abstract). Hassler et al. disclose on page 460 that our synthetic route is shown in Scheme 1. Living anionic polymerization followed by chain end modification was used to make norbornene- (NB-) functionalized macromonomers (MMs), which were then polymerized via ring opening metathesis polymerization (ROMP). ROMP has successfully been combined with living polymerization strategies such as anionic, RAFT, and ATRP and is compatible with PEO. This strategy has several advantages. First, anionic polymerization can yield low dispersity PEO and PPO polymers of a targeted molecular weight with well-defined α-chain ends. Second, ROMP of NB macromonomers reaches >99% conversion within minutes. Third, ROMP avoids chain transfer/coupling side reactions that are often observed during radical polymerization, to which PPO macromonomers are vulnerable due to the abstractable proton on the tertiary carbon site of every repeat unit. Together, these advantages enable high-throughput synthesis of high molecular weight, high grafting density, low dispersity BBPs with control over graft length and graft end group. The nomenclature adopted throughout is BB-Eq,p-b-BB-Pn,m where “BB” indicates bottlebrush, “E” and “P” indicate PEO and PPO respectively, and the subscripts are number-average degrees of polymerization in reference to Scheme 1.
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Hassler et al. disclose in Table 1materials and micellization data summary as below:
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Hassler et al. discloses in Figure 4 (a) Excess scattering intensity at 37 °C, as a function of polymer concentration. Linear PEO with an Mn = 20 kDa is a negative control for micellization. (b) Cryo-TEM micrograph of BB E(45,160)-b-BB-P(15,43) at a concentration of 10 mg/mL in aqueous buffer with 40 000× magnification. (c) Trend between CMCa and Mn for linear and bottlebrush poloxamers of similar wt % PEO. Data for linear poloxamers (40 °C) are taken from Alexandridis et al.59 Data are fit to the exponential function shown on the graph. Hassler et al. then disclose in conclusion, we report an efficient, high-throughput synthetic strategy to create bottlebrush poloxamers for the first time. The combination of living anionic and ROMP polymerization affords control over graft length and graft end group and enables quantitative conversion of the macro monomer. A series of hydrophilic bottlebrush poloxamers was synthesized over a range of molecular weights, and the micellization behavior was compared to that of linear poloxamers. Bottlebrush poloxamers exhibit a remarkably reduced driving force for micellization compared to linear poloxamers as evidenced by a 2 orders of magnitude smaller scaling exponent between Mn and CMCa (see page 464).
Claim Rejections - 35 USC § 103
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.
Note: The claims are examined with respect to the elected species wherein dexamethasone as the crystalline drug type and polylactic acid as the shell material.
Claims 1-4, 7, 9-12, and 15 are rejected under 35 U.S.C. 103 as being unpatentable over Hassler et al. (ACS Macro Lett. (2022) 11 (4): 460–467, IDS reference) in view of Johnson et al. (US2022/0370628).
Applicants’ claims
Applicants claim Applicants claim the below block copolymer:
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Claim 15 recites “A composition comprising a polymer of claim 1 and a pharmaceutically acceptable excipient and optionally further comprising a therapeutic agent.”
Determination of the Scope and Content of the Prior Art
(MPEP 2141.01)
The teachings of Hassler et al. are set forth above and are incorporated herein by reference.
Ascertainment of the Difference Between Scope of the Prior Art and the Claims
(MPEP 2141.02)
Hassler et al. do not specifically teach the inclusion of a pharmaceutically acceptable excipient and optionally further comprising a therapeutic agent with the polymer. These deficiencies are cured by the teachings of Johnson et al.
Johnson et al. teach macromonomers of Formula (I), and salts thereof; methods of preparing the macromonomers, and salts thereof; Brush prodrugs (polymers); methods of preparing the Brush prodrugs; compounds of Formula (II); conjugates of Formula (III), and salts thereof; pharmaceutical compositions comprising a Brush prodrug, or a conjugate or a salt thereof; kits comprising: a macromonomer or a salt thereof, a Brush prodrug, a compound, a conjugate or a salt thereof, or a pharmaceutical composition; methods of using the Brush prodrugs, or conjugates or salts thereof; and uses of the Brush prodrugs, and conjugates or salts thereof. These chemical entities may be useful in delivering pharmaceutical agents to a subject or cell (see abstract). compositions (e.g., pharmaceutical compositions) comprising a polymer described herein, and optionally an excipient (e.g, pharmaceutically acceptable excipient). The present disclosure also provides compositions (e.g., pharmaceutical compositions) comprising a conjugate described herein, and optionally an excipient (e.g., pharmaceutically acceptable excipient). In certain embodiments, the pharmaceutical composition described herein comprises a polymer described herein and a pharmaceutically acceptable excipient. In certain embodiments, the pharmaceutical composition described herein comprises a conjugate described herein and a pharmaceutically acceptable excipient (paragraph 0325). The ability of the brush polymers to form a micelle is described in claim 3). Pharmaceutical compositions described herein can be prepared by any method known in the art of pharmacology. In general, such preparatory methods include bringing the polymer or conjugate described herein (which may includes a therapeutic agent (the “active ingredient”)) into association with a carrier or excipient, and/or one or more other accessory ingredients, and then, if necessary and/or desirable, shaping, and/or packaging the product into a desired single- or multi-dose unit (paragraph 0329).
Finding of Prima Facie Obviousness Rational and Motivation
(MPEP 2142-2143)
It would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the instant invention to modify the teachings of Hassler et al. by including a pharmaceutically acceptable excipient and optionally further comprising a therapeutic agent with the brush polymer because Johnson et al. teach macromonomers of Formula (I), and salts thereof; methods of preparing the macromonomers, and salts thereof; Brush prodrugs (polymers); methods of preparing the Brush prodrugs; compounds of Formula (II); conjugates of Formula (III), and salts thereof; pharmaceutical compositions comprising a Brush prodrug, or a conjugate or a salt thereof; kits comprising: a macromonomer or a salt thereof, a Brush prodrug, a compound, a conjugate or a salt thereof, or a pharmaceutical composition; methods of using the Brush prodrugs, or conjugates or salts thereof; and uses of the Brush prodrugs, and conjugates or salts thereof. These chemical entities may be useful in delivering pharmaceutical agents to a subject or cell (see abstract). One of ordinary skill in the art would have been motivated to do so because Johnson et al. demonstrates the use of brush polymers for the delivery of active agents by stating that compositions (e.g., pharmaceutical compositions) comprising a polymer described herein, and optionally an excipient (e.g, pharmaceutically acceptable excipient). The present disclosure also provides compositions (e.g., pharmaceutical compositions) comprising a conjugate described herein, and optionally an excipient (e.g., pharmaceutically acceptable excipient). In certain embodiments, the pharmaceutical composition described herein comprises a polymer described herein and a pharmaceutically acceptable excipient. In certain embodiments, the pharmaceutical composition described herein comprises a conjugate described herein and a pharmaceutically acceptable excipient (paragraph 0325). The ability of the brush polymers to form a micelle is described in claim 3). Pharmaceutical compositions described herein can be prepared by any method known in the art of pharmacology. In general, such preparatory methods include bringing the polymer or conjugate described herein (which may includes a therapeutic agent (the “active ingredient”)) into association with a carrier or excipient, and/or one or more other accessory ingredients, and then, if necessary and/or desirable, shaping, and/or packaging the product into a desired single- or multi-dose unit (paragraph 0329). One of ordinary skill in the art would have had a reasonable chance of success in combining Hassler et al. and Johnson et al. because both references are drawn to bottle brush polymers.
In light of the forgoing discussion, the Examiner concludes that the subject matter defined by the instant claims would have been obvious within the meaning of 35 USC 103. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art before the effective filing date of the instant invention, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to TIGABU KASSA whose telephone number is (571)270-5867. The examiner can normally be reached on 8 AM-5 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, David Blanchard can be reached on 571-272-0827. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/TIGABU KASSA/Primary Examiner, Art Unit 1619
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