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 .
Priority
Provisional application filed 03/30/2022 is acknowledged. Further, it is acknowledged that the present application is a 371 of international PCT/US23/16929 filed 03/30/2023. However, it is noted that the provisional application does not disclose the PEGylated nanogel of instant claims 1-11 and 13, and as such the effective filing date for these claims is 03/30/2023.
Election/Restrictions
Applicant’s election with traverse of Group I (claims 1-11 and 13) in the reply filed 08/04/2026 is acknowledged. Further, the election of species for claims 2-3, 5, and 8-9 in the reply is acknowledged. The traversal is on the ground(s) that the group of claims do not lack a single general inventive concept in view of Malkoch (US 20210299061 A1), stating that the instant claims are directed to biomolecule binding nanogel systems where functionalized telodendrimers provide selective biomolecule capture through size-exclusion. Applicant further states that instant claims describe that the telodendrimers are bonded to the polymer chain by at least one double bond.
This is not found persuasive because group III (claims 14-20) is drawn to a biomolecule-binding hydrogel composition where the core comprises a crosslinked hydrogel system, and telodendrimers comprising a plurality of charged and hydrophobic binding moieties. Independent claim 14 and dependent claims 15-20 do not recite the requirement where functionalized telodendrimers provide selective biomolecule capture based on size exclusion. Claims 14-20 further do not describe that the telodendrimers are bonded to the polymer chain by at least one double bond. While Applicant is correct in that Malkoch does not teach the concept of the functionalized telodendrimer that allows for chemical binding functionality and physical size-exclusion properties, this is also not recited in the claims of group III, so it is not the shared technical feature among groups I, II, and III. Therefore, the shared technical feature between groups I, II, and III is the biomolecule-binding nanogel composition with a crosslinked hydrogel system, which as stated in the restriction requirement, does not make a contribution over Malkoch. The injectable nanogel of Malkoch can be used to encapsulate proteins (i.e. biomolecules, para. [0076]), and comprises dendrimers and hydrophilic and hydrophobic monomers (para. [0010]).
The requirement is still deemed proper and is therefore made FINAL.
Claims 12 and 14-20 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention.
Claims 1-11 and 13 are pending and under current examination.
Claim Interpretation
The limitation of instant claim 1, disclosing that the bond between the telodendrimer and the polyethylene glycol polymer (PEG) chain is polymerized by at least one double bond located between the PEG and the dendritic telodendrimer, is interpreted to be a product-by-process claim. The presence of the double bond between the PEG and the telodendrimer is found during the polymerization process. This process is described in instant specification, which describes that the double bonds were introduced into the telodendrimer through the reaction between an acryloyl chloride and a primary amine (para. [0137]). Therefore, the double bond limitation of instant claim 1 is interpreted to be found in the polymerization process, but is not necessary in the final structure of the nanogel.
Claim Objections
Claims 2-4 are objected to because of the following informalities: they cite their dependency from claim 1, and have the phrase “…wherein nano-sized crosslinked hydrogel system is…”, which appears to be a typographical error. For the purposes of examination, the phrase in claims 2-4 is interpreted to read “…wherein the nano-sized crosslinked hydrogel system is…”. Appropriate correction is required.
Claim 8 is objected to because of the following informalities: it cites its dependency from claim 1, and has the phrase “…wherein hydrophobic group is at least one selected from…”, which appears to be a typographical error. For the purposes of examination, the phrase in claim 8 is interpreted to read “…wherein the hydrophobic group is at least one selected from…”. 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.
Claim(s) 9 and 10 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or joint inventor regards as the invention.
Regarding claim 9, the claim cites its dependency from claim 1, and has the phrase “the charged binding moiety”, which lacks antecedent basis. For the purpose of examination, the phrase is best interpreted to read “the hydrophilic charged binding moiety”.
Regarding claim 10, the claim cites its dependency from claim 1, and states “wherein the hydrophobic binding group is heptadecanoic acid (C17) and the charged binding moiety is arginine (Arg)”, which lacks antecedent basis. For the purpose of examination, the claim is interpreted to read, “wherein the hydrophobic group is heptadecanoic acid (C17) and the hydrophilic charged binding moiety is arginine (Arg)”.
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.
Claim(s) 1 and 6-13 are rejected under 35 U.S.C. 103 as being unpatentable over Luo (US 20210269601 A1) in view of Yang (US 20110189291 A1).
Regarding claims 1 and 13, Luo teaches telodendrimers that can be charged and have crosslinking groups, and aggregate to form nanoparticles (see abstract) that are spherical (para. [0131]). The telodendrimers comprise functional hydrophilic and hydrophobic segments (para. [0008]), where the charged and hydrophilic moieties in telodendrimers allow for protein binding (i.e. biomolecule binding, para. [0018]). Luo describes that the telodendrimers can be bonded to polyethylene glycol (PEG) groups that form a PEG layer, which serves as a stealth hydrophilic shell (i.e. PEG extend to surface of nanoparticle, para. [0066]). The size-exclusivity component of the nanogel network of instant claim 1 would be inherent with the composition of Luo, since Luo describes each component of the telodendrimers crosslinked to PEG groups, which make up the surface of a nanoparticle. Luo further teaches that the nanogel formulation can be used for parenteral administration (i.e. injectable, para. [0110, 0117]).
While Luo teaches the claimed invention as above, and teaches that the telodendrimer is bonded to the PEG linear chain, it fails to teach that the telodendrimer is polymerized in the hydrogel system by at least one double bond between the PEG and functionalized telodendrimer. Yang teaches hydrogels that include dendrimers to which polymer chains, such as polyethylene glycol, have been conjugated to (see abstract). The PEG polymer chains bonded to the dendrimers are further crosslinked (para. [0013]). Yang describes that the PEG chains were acrylated first then conjugated to the amine-terminated dendrimers (para. [0094]). The acrylated PEG has an acryloyl moiety, which reacts with the amine of the dendrimer to bond the PEG linear chain to the dendrimer. As described in instant specification, the double bonds of instant claim 1 were introduced into the telodendrimer through the reaction between the acryloyl chloride and primary amine (para. [0137]). Thus, it is inherent that the reaction described in Yang, which also includes a reaction between an acryloyl functional group and an amine, would also include a double bond during polymerization.
Luo and Yang are considered to be analogous to the claimed invention because they are in the same field of hydrogels that can bind to biomolecules. Luo fails to teach the method of polymerization to bond the telodendrimer to the PEG linear chain, however, as above, Yang describes a process to conjugate the dendrimer to a PEG chain in a hydrogel. A person of ordinary skill in the art would be motivated to use the process described in Yang to conjugate the PEG chain and the dendrimer of Luo, as Yang teaches a method that is effective when forming a hydrogel system. MPEP § 2143(I)(g).
Regarding claim 6, Luo teaches that the nanoparticles are in the size range of 5 to 50 nm (para. [0088]). The size range of the nanoparticles described in instant claim 6 overlaps with the range of Luo and as such a prima facie case of obviousness exists. MPEP § 2144.05(I).
Regarding claim 7, Luo teaches that the polyethylene glycol that is bonded to the telodendrimer has a molecular weight of 44 Da to 100,000 Da (see claim 1). The molecular weight range of the polyethylene glycol claimed in instant claim 7 is fully encompassed by that of Luo, and as such is obvious. MPEP § 2144.05(I).
Regarding claims 8-10, Luo teaches that the telodendrimers comprise hydrophobic moieties such as heptadecanoic acid (para. [0126]), and arginine moieties (see claim 6).
Regarding claim 11, Luo teaches that the telodendrimers can bind to proteins (para. [0134]).
Claim(s) 2 and 3 are rejected under 35 U.S.C. 103 as being unpatentable over Luo (US 20210269601 A1) in view of Yang (US 20110189291 A1), in further view of Kannan (US 20130136697 A1), and in further view of Kusch (Journal of Analytical and Applied Pyrolysis, 2015, 113, 412-418), hereinafter Kusch.
While Luo and Yang teach the claimed invention as above, they fail to teach the specific hydrophilic monomer that polymerizes the hydrogel system.
Regarding the elected species of the hydrophilic monomer of claims 2 and 3, Kannan teaches injectable hydrogels that comprise nanoparticles made up of dendrimers (see abstract), where the nanoparticles are involved in the conjunction of drugs. The nanoparticles include crosslinked hydrogels (i.e. nanosized hydrogels, para. [0008]), and polyethylene glycol (PEG) is used as a polymer (see claim 16). Kannan teaches that the PEG can have a methacrylate termination group (para. [0046]), describing a compound with the same general structure as a tetraethylene glycol methyl ether methacrylate.
Luo, Yang, and Kannan are considered to be analogous to the claimed invention because they are in the same field of nanogel formulations for injectable administration. One of ordinary skill in the art would be motivated to incorporate the PEG with a methacrylate termination group of Kannan into the formulation of Luo, to form an injectable hydrogel. One of ordinary skill in the art would be motivated to combine these elements, as Kannan teaches a formulation that is effective for the benefit of delivering the nanoparticles throughout the body for therapeutic treatment (see abstract). MPEP § 2143(I)(a).
Kusch teaches that copolymers based on polyethylene glycol methyl ether methacrylate are useful due to their unique properties, and are ideal candidates specifically in morphology of micelles (pg. 413, col. 1, line 17). Kusch describes copolymers that are synthesized by copolymerization of macromonomers, which are produced by a reaction of polyethylene glycol and a methacrylate backbone (pg. 412, col. 2, line 17). The corresponding di methacrylate are crosslinkers for the production of hydrogels (pg. 413, col. 1, line 2). Kusch further teaches tetraethylene glycol methyl ether methacrylate specifically (see Table 1).
Luo, Yang, Kannan, and Kusch are considered to be analogous to the claimed invention because they are in the same field of biocompatible polymers that comprise PEG. One of ordinary skill in the art would be motivated to substitute the methacrylate terminated PEG of Kannan, with a tetraethylene glycol methyl ether methacrylate as described in Kusch, because the methacrylate terminated PEG polymer has the same general structure as tetraethylene glycol methyl ether methacrylate, and as such will have similar properties to yield predictable results. MPEP § 2143(I)(b).
Claim(s) 4 is rejected under 35 U.S.C. 103 as being unpatentable over Luo (US 20210269601 A1) in view of Yang (US 20110189291 A1), in further view of Kannan (US 20130136697 A1), and in further view of Koide (Nature Communications, 2021, 12, 1-14), hereinafter Koide.
While Luo, Yang, and Kannan, teach the claimed invention as above, they fail to teach the crosslinker monomer and crosslinker molar ratio of the composition.
Regarding claim 4, Kannan describes that in the formation of the hydrogels, the crosslinking agent was used in an excess of molar ratio relative to the PEG polymer, but as a result the obtained gels were not pourable (para. [0128]). Kannan further does not disclose what amount of the crosslinker monomers was then most effective to allow formation of an injectable hydrogel. Koide teaches a nano-sized hydrogel that can bind to biomolecules, and is injected (see abstract). Koide teaches evaluating nanoparticles that have a high affinity to proteins, that are lightly (2%) crosslinked (pg. 2, col. 2, line 28). The crosslinker ratio described in instant claim 4 overlaps with the concentration disclosed in Koide, and as such is obvious.
Luo, Yang, Kannan, and Koide are considered to be analogous to the claimed invention because they are in the same field of hydrogels that are composed of crosslinked polymers. As above, Kannan describes that when the molar ratio of the crosslinking agent was in excess, the hydrogels were not pourable, teaching that the molar ratio of the crosslinking agent is an optimizable parameter, inviting one skilled in the art to experiment. It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to substitute the concentration of crosslinkers in Koide, into the composition of Luo to yield predictable results, since Koide teaches that this concentration of crosslinkers is effective to develop an injectable, nano-sized hydrogel that can has a high affinity to proteins. MPEP § 2143(I)(b).
Claim(s) 5 is rejected under 35 U.S.C. 103 as being unpatentable over Luo (US 20210269601 A1) in view of Yang (US 20110189291 A1), in further view of Kannan (US 20130136697 A1), and in further view of Chen (Polymer, 2018, 146, 378-385), hereinafter Chen.
While Luo, Yang, and Kannan teach the claimed invention as above, they fail to teach the specific biodegradable crosslinker elected for claim 5.
Regarding the elected species of the crosslinker of claim 5, Chen teaches the synthesis of spherical polymers comprising polymeric arms that extend from a crosslinked core (see abstract). The linear polymers of Chen include poly(ethylene glycol) methyl ether methacrylate, which were polymerized with N,N'-bis(acryloyl)cystamine (BAC) as a crosslinker (see abstract). Chen describes that N,N'-bis(acryloyl)cystamine (BAC) is commonly applied to prepare bioreducible biomaterials such as core crosslinked micelles and nanogels (pg. 379, col. 1, line 16).
Luo, Yang, Kannan, and Chen are considered to be analogous to the claimed invention because they are in the same field of methods for crosslinking biocompatible polymers. One of ordinary skill in the art would be motivated to use BAC as a crosslinker for polymers such as the polyethylene glycol methyl ether methacrylate described in both Kannan (see claim 18) and Chen. Chen teaches that the polyethylene glycol methyl ether methacrylate polymers could successfully be crosslinked with the BAC, and as such one of ordinary skill in the art would have a reasonable expectation of success in incorporating the BAC of Chen as a crosslinker for the polyethylene glycol methyl ether methacrylate of Kannan. MPEP § 2143(I)(a).
Conclusion
Claim(s) 1-11 and 13 are rejected.
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/BETHANY P BARHAM/Supervisory Patent Examiner, Art Unit 1611
/M.R.M./Examiner, Art Unit 1611
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