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 .
DETAILED ACTION
Applicant’s arguments, filed 4/14/2026, have been fully considered but they are not deemed to be fully persuasive. Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objects are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
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 1-9, 11-16, and 20-25 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2006/126095 to Hitz (IDS filed 1/26/2021) in view of WO 2017/055536 to Geraths (IDS filed 1/27/2021). Hitz teaches a copolymer containing multiple molecules of an active agent, comprising polymerization of a reaction mixture comprising (1) one or more polymerizable principal monomers, which monomers are characterized as having at least one vinylic group and not containing an amino acid residue, such as 2-phenylethylacrylate, 2-phenylethylmethacrylate and butanedioldiacrylate (example 20), and 2-hydroxyethylmethacrylate, and ethylene glycol diacrylate (example 21)); one or more co-principal monomers of formula I or II in which at least one of Y and Z is H (examples 20 and 21); an initiator system for generating free radical species such as di-(tert-butylcyclohexyl)peroxydicarbonate and azobisisobutyronitrile) (examples 20-21), the polymerization yielding a copolymer, coupling of the active agent to the copolymer after polymerization of the reaction mixture (abstract; page 2, first full paragraph to page 7, first full paragraph; Examples 20-22). This is a copolymer containing multiple molecules of an active agent made by polymerization of a reaction mixture comprising one or more polymerizable principal monomers, which monomers are characterized as having at least one vinylic group and not containing an amino acid residue, one or more co-principal monomers corresponding to applicant’s formulae I or II in which at least one of Y and Z is H, an initiator system for generating free radical species, the polymerization yielding a copolymer; and coupling of the active agent to the copolymer after polymerization of the reaction mixture. The active agents may be hydrophobic steroids, triamcinolone, anecortave acetate, and dexamethasone loaded onto (coupled to) the polymer (dexamethasone is used to treat cancer; an intercalating drug; an anti-inflammatory substance) (Examples 20-22).
Hitz fails to teach an agent for controlling radical polymerization. Hitz further fails to teach covalent bonding of the active agent.
Geraths teaches a copolymer made by polymerization of a reaction mixture (a polymerization mixture), comprising one or more polymerizable principal monomers, which monomers are characterized as having at least one vinylic group and not containing an amino acid residue, one or more co-principal monomers of formulae I or II in which at least one of Y and Z is H (step (b) and (c), an agent for controlling radical polymerization (chain transfer agent), and an initiator system for generating free radical species (free radical initiator), the polymerization yielding a copolymer (abstract; page 1, first paragraph; page 4, bottom paragraph to page 9, second full paragraph; claim 1) and is therefore in the same field of invention as Hitz. Geraths teaches that incorporation of an agent for controlling radical polymerization desirably produces less polydispersity and a narrower size distribution (pages 16-17, bridging paragraph). Geraths teaches a copolymer containing multiple molecules of an active agent made by polymerization of a reaction mixture (a polymerization mixture), comprising one or more polymerizable principal monomers, said monomers are characterized as having at least one vinylic group and not containing an amino acid residue, one or more co-principal monomers of formulae I or II in which at least one of Y and Z is H (steps (b) and (c)), an agent for controlling radical polymerization (chain transfer agent),and an initiator system for generating free radical species (free radical initiator), the polymerization yielding a copolymer (abstract; page 1, first paragraph; page 4, bottom paragraph to page 9, second full paragraph; claim 1). Geraths teaches use of functionalized co-principal monomers of formula I, formula II, or a combination (Example 17), wherein the hydrophobic side chain linked amino acids of formula I or formula II have their alpha-amino and/or carboxyl groups functionalized with alkyl or cholesteryl residues and other hydrophobic monomers (pages 30-31, bridging paragraph). The functionalized alkyl or cholesteryl residues and other hydrophobic monomers are taught to have high capacity for binding water molecules and enhanced surface wettability and lubricity. This is a copolymer containing multiple molecules of an active agent made by polymerization of a reaction mixture comprising one or more polymerizable principal monomers, which monomers are characterized as having at least one vinylic group and not containing an amino acid residue, one or more co-principal monomers corresponding to applicant’s formulae I or II in which at least one of Y and Z is H, an agent for controlling radical polymerization and an initiator system for generating free radical species, the polymerization yielding a copolymer; and coupling of the active agent to the copolymer after polymerization of the reaction mixture. Geraths teaches an average molecular weight of the copolymer of 5,000 to 100, 000 Daltons for at least 80% of the copolymer (pages 8-9, bridging paragraph; claim 3). The agent for controlling radical polymerization (chain transfer agent) is a RAFT agent (pages 16-17, bridging paragraph; Examples 14 and 17; claims 4 and 13). Geraths teaches two success polyermization reactions for the copolymer, wherein the first polymerization reaction is carried out in a first reaction mixture comprising one or more polymerizable principal monomers not containing an amino acid group, a RAFT agent for controlling the copolymerization, and an initiator system for generating free radical species, the polymerization yielding a RAFT pre-polymer (Step A, page 31), and wherein the second polymerization reaction is carried out in a second reaction mixture comprising the RAFT pre-polymer of the first polymerization reaction, one or more co-principle monomers of formulae I and/ or II, and an initiator system for generating free radical species (Step B, page 32), wherein the RAFT agent may be used in Example 17 is 2-(dodecylthiocarbonothioylthio)-2- methylpropionic acid(Example 17) which comprises a monodisperse spacer of 5-25 units, a carboxyl group (comprising a carboxyl group) which may be used for functionalization of the copolymer with a cell type-specific or a tissue type-specific targeting moiety (claims 7-8 and 14-15).
It would have been obvious to one of ordinary skill in the art at the time the invention was made to use an agent for controlling radical polymerization in the method of making of Hitz. The motivation for this would be to control radical polymerization in the preparation of the polymer to provide a narrow size distribution and smaller polydispersity. A smaller polydispersity in the polymer network would aid in providing a uniform distribution of the active agent, as desired by Hitz (pages 18-19, bridging paragraph). Regarding claim 24, which recites the copolymer of claim 1, “wherein the tracer molecule is a fluorophore,” and claim 25, which recites the copolymer of claim 11, “wherein the tracer molecule is a fluorophore,” these claims limit the member of the Markush group in the base claims wherein the active agent is a tracer molecule, but do not positively recite that the tracer molecule is a fluorophore. As the art currently applied reads on that embodiment of the Markush group in the independent claims wherein the active agent is cytotoxic agent or an anti-inflammatory substance, it is deemed to also read on claims 24-25, which limit the tracer molecule in the Markush group of claims 1 and 11, but do not positively recite that the tracer molecule is present. It would have been further obvious to try covalent bonding as the means of connecting the active agent to the carrier. The motivation for this would be to ensure the active agent stayed attached to the carrier until it was administered. It would be well within the purview of the artisan to decide between the limited choices of covalent and non-covalent bonding.
Applicant’s arguments have been fully considered but are not found persuasive. Regarding applicant’s arguments regarding covalent bonding, the examiner’s response is that the active agent is coupled to the copolymer as set forth above, and the artisan would understand in chemically coupling of one agent to another, there are only a few choices, and owing to the few choices, the artisan would arrive at covalent coupling through routine experimentation.
Regarding applicant’s argument that there is no chemical coupling taught in the first place, and therefore no choice of covalent vs. non-covalent coupling, the examiner’s response is that Hitz teaches a copolymer containing multiple molecules of an active agent, comprising polymerization of a reaction mixture which yields a copolymer and coupling of the active agent to the copolymer after polymerization of the reaction mixture (abstract; page 2, first full paragraph to page 7, first full paragraph; Examples 20-22). This is a teaching of chemical coupling. Regarding applicant’s that the polymers of Hitz comprise a non-functionalized amino acid moiety which are excluded from the invention, the examiner’s response is that the present claims use the term “comprising” to describe the components of the reaction mixture, and the reaction mixture is therefore open to monomers not enumerated in the claim, including monomers comprising non-functionalized amino acids. Regarding applicant’s argument that the art does not teach that the copolymer is functionalized with a cell type-specific or tissue type-specific targeting moiety, the examiner’s response is that Geraths teaches wherein the RAFT agent may be used in Example 17 is 2-(dodecylthiocarbonothioylthio)-2- methylpropionic acid(Example 17) which comprises a monodisperse spacer of 5-25 units, a carboxyl group (comprising a carboxyl group) which may be used for functionalization of the copolymer with a cell type-specific or a tissue type-specific targeting moiety (claims 7-8 and 14-15). Regarding applicant’s reiteration that the examiner has not established that it would have been obvious to try covalent bonding, the examiner’s response is that it would have been obvious to try covalent bonding as the means of connecting the active agent to the carrier. The motivation for this would be to ensure the active agent stayed attached to the carrier until it was administered. It would be well within the purview of the artisan to decide between the limited choices of covalent and non-covalent bonding. As there are only two choices, it would have been obvious to try either, including covalent bonding.
Claims 1-17 and 20-25 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2017/055536 to Hitz in view of Geraths in further view of Willcock (Polym. Chem., 2010). The relevant portions of Geraths are given above.
Hitz and Geraths fail to teach wherein the RAFT group of the RAFT agent is eliminated subsequent to polymerization or functionalization of the polymer.
Willcock teaches that failure to remove the RAFT group functionality of RAFT agents subsequent to polymerization or functionalization of polymers prepared by RAFT polymerization leaves residual RAFT agent functionality within the polymer which poses a problem due to the agent’s inherent reactivity and decomposition into sulfur-containing materials) (page 150, right column, first full paragraph). Accordingly, the RAFT group is conventionally removed (eliminated) to avoid such complications by several methods known in the art (page 150, right column, second full paragraph to page 151, left column, second full paragraph).
It would have been obvious to one of ordinary skill in the art at the time the invention was filed to eliminate the RAFT group of the RAFT agent subsequent to polymerization or functionalization of the polymer. The motivation for this is to avoid residual activity of the RAFT group within the polymer which poses problems due to the agent’s inherent reactivity and decomposition into sulfur-containing materials.
Applicant’s arguments have been fully considered but are not found persuasive. Regarding applicant’s arguments in relation to Hitz and Geraths, these were addressed above. Willocck was relied on for its teaching that failure to remove the RAFT group functionality of RAFT agents subsequent to polymerization or functionalization of polymers prepared by RAFT polymerization leaves residual RAFT agent functionality within the polymer which poses a problem due to the agent’s inherent reactivity and decomposition into sulfur-containing materials) (page 150, right column, first full paragraph). Accordingly, the RAFT group is conventionally removed (eliminated) to avoid such complications by several methods known in the art (page 150, right column, second full paragraph to page 151, left column, second full paragraph). It would have been obvious to eliminate the RAFT group of the RAFT agent subsequent to polymerization or functionalization of the polymer. The motivation for this is to avoid residual activity of the RAFT group within the polymer which poses problems due to the agent’s inherent reactivity and decomposition into sulfur-containing materials.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to PAUL W DICKINSON whose telephone number is (571)270-3499. The examiner can normally be reached on M-F 9 AM to 7:30 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached on 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL W DICKINSON/Primary Examiner, Art Unit 1618
June 3, 2026
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