DETAILED ACTION
Notice of Pre-AIA or AIA Status
This Office action details a first action on the merits for the above referenced application No. Claims 1-37 are pending in this application. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/04/2024, 07/16/2024 and 07/24/2024 was noted and the submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings were received on 07/25/2023 and 10/09/2023. These drawings are acknowledged.
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) 1-19, 21, 26-29, and 31-37 are rejected under 35 U.S.C. 103 as being unpatentable over Bright (US 2016/0317621) in view of Pathak et al. (US 2022.0118416).
Bright discloses a hydrogel for chemical ablation comprising cross-linked gels, in which two precursor solutions are typically mixed containing functional groups that react with each other to form a crosslinked gel, by varying the ratio of the precursor solutions, the concentration of an accelerator or crosslinking agent. One of the precursor solutions (A) is delivered first to fill the target levels followed by the second precursor solution (B) which crosslinks with precursor A from the distal to proximal target sites. In another embodiment, the precursor solution A is delivered first followed by the 50/50% mix of the two precursor solutions. In one embodiment the ablative agent is a neurolytic agent delivered in a gel. This approach may be utilized to treat other cardiac and pulmonary diseases. (A/B) (reads on infused hydrogel) ( abstract and 0356-0357). The precursors may be a combination of an ester group on one PEG (precursor A) and a trilysine amine (precursor B). In some embodiments, the precursor A is a 20 kDa N-hydroxysuccinimide end capped PEG which is resuspended at the time of delivery in sodium phosphate buffer, the accelerator (reads on activation solution). The precursor B can be, in some cases, a trilysine acetate in a 0.075 M sodium borate decahydrate buffer (pH 10.2) (0364). In one embodiment, the delivery of 15 to 20 ml of a neuroablative agent to one level is as effective at achieving multi-level ablation (0112). In one embodiment, disclosed a systems and methods for neuromodulating sympathetic nerves of a patient that includes delivering a gel, such as a hydrogel to the paravertebral gutter. The hydrogel could include, for example, an insitu polymerizing hydrogel, or an injectable hydrogel slurry and delivery of electromagnetic energy, such as RF, microwave, and/or ultrasound energy to a desired anatomic location (0011). The gel could include a biodegradable or bioerodable polymer, or an injectable hydrogel. . In one embodiment the neurolytic agent (therapeutic agent) is coadministered with the hydrogel in an aqueous/ethanol solution (reads on ablation composition). The ethanol, between, for example, 10 and 50 wt %, more preferably 30%, can be incorporated in a HA- or PEG-based hydrogel (0386). In one embodiment solutions of covalently crosslinked multi-armed PEG hydrogel particles of about 70 μm in diameter are formulated in a PEG (20 kDa) water solution to improve the injectability of the slurry (0466). In one embodiment, a hydrogel such as one from the group of in situ polymerizing poly(ethylene glycol)-based hydrogels is selected for the delivery of drugs. Crosslinked PEG-based polymers are biocompatible, have controlled crosslinking, and relatively high adhesion strength. In particular the use of multi-arm PEGs, such as 4-armed PEG that are functionalized to cross-link with one another can be of interest. The molecular weights of the PEG arms, preferably between about 1 kDa and 8 kDa (0363). The drug delivery systems may be comprised of functionalized linear PEG or multi-arm PEG derivatives. PEG may be functionalized with an amine group (or other acid reactive chemical group) that binds to a carboxylic group (or other amine reactive group). These include 3 arm PEG amine (-NH2), 4 arm PEG amine (-NH2), 4 arm PEG carboxyl (-COOH), 4 arm PEG SCM (4 arm PEG NHS ester), 4 arm PEG succinimidyl glutaramide (-SGA) 4 arm PEG Nitrophenyl carbonate (-NPC) with a carbonate linker between the PEG and NHS ester, 4 arm PEG succinimidyl carbonate (-SC) with a carbonate linker, 4 arm PEG Maleimide (-MAL) which is selective for thiol groups and reacts at pH 5-6.5, 4 arm PEG succinimidyl succinate (-SS) with a cleavable ester linker to make it a biodegradable hydrogel, 4 arm PEG succinimidyl Glutarate (-SG) with a ester linker, 4 arm PEG Isocianate, 4 arm PEG Azide, 4 arm PEG norbornene (0372). A contrast agent (iohexol) can be mixed with neuroablative agent and the spread of the agent can be confirmed intraprocedurally (0120). Additional disclosure includes that chemical ablation may be desirable over thermal ablation approaches in some cases because it may reduce or eliminates pain and unpleasant sensations during the procedure. (0472).
Bright fails to disclose visualization agent and free radical polymerizable groups such as acrylate and methylacrylate functional groups in the hydrogel composition.
Pathak discloses a composition comprising a biodegradable crosslinked polymer unibody implant or microparticle comprising two or more layers wherein one layer comprises a drug and the other layer comprises a visualization agent. The preferred crosslinked material is organic solvent gel or hydrogel and is made using either condensation polymerization or free radical polymerization (0017). The precursor polymerization may be conducted in presence of the drug and/or visualization agent to produce an organogel comprising drug or visualization agent (0141). The preferred compositions in 2D and 2E have a central core extended with biodegradable blocks and terminated with 2 or more functional reactive groups such as electrophilic groups (204). The other precursor shown in FIG. 2E also has a central core (201) extended with (203) biodegradable block and terminated with functional reactive groups such as nucleophilic groups (205). For example, when electrophilic groups are activated esters, the nucleophiles can be either amines or anilines and covalent bonds formed are of carboxamides; when electrophilic groups are acyl nitrile, and nucleophilic groups are aniline or amine, then covalent bonds formed are of carboxamides (0150). In one illustrative embodiment, PEG10Kurethane diacrylate and PEG10Kurethane diacrylate with PLGA based organic solvent gels are prepared (0154). In one embodiment, includes coloring compositions that is suitable for human or animal implantation and are preferably approved by FDA for use in implantable medical devices or in pharmaceutical preparations, especially injectable pharmaceutical preparations. The compounds include but are not limited to: Methylene blue; Indocyanine green, Eosin Y; Ethyl Eosin, Fluorescein sodium; Chromium-cobalt-aluminum oxide; Ferric ammonium citrate and the like (0104).
NOTE: With respect to the ratio of electrophilic functional groups to nucleophilic functional groups (0.8 : 1.0 to 1.0 :0.8) and hydrogel precursor solution and the activator solution (1:1 to about 20:1) would have been obvious to one of ordinary skill in the art at the time the invention was made to modify the teachings of Bright and Pathak by determining the optimum weight ratio of electrophilic to nucleophilic functional groups (0.8 : 1.0 to 1.0 :0.8) and hydrogel precursor solution and the activator solution that will result in a composition that will be suitable to ablate tissue in contact with the hydrogel (claims 7, 35 and 37). Pathak discloses that the effective polymerization and crosslinking of precursors via condensation polymerization and the crosslinking density is controlled by varying the total number of reactive groups in the precursors (total of electrophilic and nucleophilic groups) and may typically contain 5, 6, 7, 8, 9,10, 11,12, 13, 14, 15, 16 or more reactive groups (0378). Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233,235 (CCPA 1955) ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997)
It would have been obvious to one of ordinary skill in the art at the time the invention was made to incorporate visualization agents and as acrylate and methylacrylate functional into Bright’s hydrogel composition. The person of ordinary skill in the art would have been motivated to make those modifications because Pathak teaches that visualization agent helps to visualize the human body/tissue using the naked human eye or using machine assisted viewing (0115) and reasonably would have expected success because visualization agents such as coloring or medical agents when added to the composition assist in the delivery of the composition and to follow its degradation after implantation (0180).
Claim(s) 20, 22-25, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Bright (US 2016/0317621) in view of Pathak et al. (US 2022.0118416) as applied to claims 1-19, 21, 26-29, and 31-37 above, and further in view of Campbell et al. (US 2014/0363382) and King (US 2009/0220578) .
The teachings of Bright (US 2016/0317621) and Pathak et al. (US 2022.0118416) are delineated above. None of these teach solution comprising initiator such as peroxide group, dicumyl peroixde or co-initiator such as Fe2+, Cr2+ or Cu2+ and solid content in the hydrogel composition.
Campbell discloses implantable material comprising filling a site with flowable precursors that set-up to make a hydrogel implant that provides for ready visualization of margins of the implant site. A crosslinked hydrogel can be formed in-situ that supports tissue around a lumpectomy site to stabilize the tissue at the margins of the lumpectomy so the margins can be precisely targeted by subsequent treatments, for instance, radiation or ablation (abstract and 0005). Hydrogels may be made from precursors. The precursors can be polymerizable and include crosslinkers that are often, polymerizable precursors. Campbell discloses that some precursors react by a chain growth mechanism by the reaction of monomers or macromonomers with a reactive center. The reactive center is commonly radical, anionic, or cationic in nature, but can also take other forms. Chain growth systems include free radical polymerization, which involves a process of initiation, propagation and termination. Initiation is the creation of free radicals necessary for propagation, as created from radical initiators, e.g., organic peroxide molecules (0048-0051). Some precursors react using initiators, capable of initiating a free radical polymerization reaction. For instance, it may be present as a pendent group on a precursor. Initiator groups include thermal initiators, photoactivatable initiators, and oxidation-reduction (redox) systems. Examples of thermally reactive initiators include 4,4' azobis(4-cyanopentanoic acid) groups, and analogs of benzoyl peroxide groups. Metal ions (co-initiator) may be used either as an oxidizer or a reductant in redox initiating systems. For example, ferrous ions may be used in combination with a peroxide or hydroperoxide to initiate polymerization, or as parts of a polymerization system. Potentially suitable metal ions for either role are any of the transition metal ions, lanthanides and actinides, which have at least two readily accessible oxidation states. Particularly useful metal ions are ferric/ferrous; cupric/cuprous; ceric/cerous; cobaltic/cobaltous; vanadate V vs. IV; permanganate; and manganic/manganous. Peroxygen containing compounds (initiator), such as peroxides and hydroperoxides, including hydrogen peroxide, t-butyl hydroperoxide, t-butyl peroxide, benzoyl peroxide, cumyl peroxide may be used (0079-0080). Hydrogels may be formed from natural, synthetic, or biosynthetic polymers. Synthetic hydrogels may be biostable or biodegradable or biodegradable. The precursors may thus be small molecules, such as acrylic acid or vinyl caprolactam, larger molecules containing polymerizable groups, such as acrylate capped polyethylene glycol (PEG-diacrylate), or other polymers containing ethylenically-unsaturated groups (0054). In some embodiments, each precursor is multifunctional, meaning that it comprises two or more electrophilic or nucleophilic functional groups, such that a nucleophilic functional group on one precursor may react with an electrophilic functional group on another precursor to form a covalent bond. At least one of the precursors comprises more than two functional groups, so that, as a result of electrophilic-nucleophilic reactions, the precursors combine to form crosslinked polymeric products (0056). A precursor may also be a macromolecule (or macromer), which is a molecule having a molecular weight in the range of a thousand to many millions (0058). Precursors may have, e.g., 2-100 arms, some embodiments are precursors with between 3 and 300 arms (0063). In some embodiments, precursors have a polymerizable group that is activated by photoinitiation or redox systems as used in the polymerization arts, e.g., or electrophilic functional groups that are carbodiimidazole, sulfonyl chloride, chlorocarbonates, n-hydroxysuccinimidyl ester, succinimidyl ester or sulfasuccinimidyl esters, the nucleophilic functional groups may be, for example, amine, hydroxyl, carboxyl, and thiol (0072). The precursors have functional groups that react with each other to form the material, the functional groups may be, e.g., a strong electrophilic functional group, meaning an electrophilic functional group that effectively forms a covalent bond with a primary amine in aqueous solution at pH 9.0 at room temperature and pressure and/or an electrophilic group that reacts by a of Michael-type reaction. The strong electrophile may be of a type that does not participate in a Michaels-type reaction or of a type that participates in a Michaels-type reaction. Examples of strong electrophiles that do not participate in a Michaels-type reaction are: succinimides, succinimidyl esters, or NHS-esters. Examples of Michael-type electrophiles are acrylates, methacrylates, methylmethacrylates, and other unsaturated polymerizable groups (0076-0078). In one embodiment, a visualization agent is used with the hydrogel to reflect or emits light at a wavelength detectable to a human eye so that a user applying the hydrogel could observe the gel. Biocompatible visualization agents are FD&C BLUE #1, FD&C BLUE #2, and methylene blue and present in the final electrophilic-nucleophilic reactive precursor species mix at a concentration of more than 0.05 mg/ml and preferably in a concentration range of at least 0.1 to about 12 mg/ml. These concentration ranges can give a color to the hydrogel without interfering with crosslinking times (as measured by the time for the reactive precursor species to gel) (0106-0108). One embodiment involves using branched precursors that have a covalently attached RO agent, so that the hydrogel will have the radioopaque (RO) agent covalently attached upon its formation from mixtures of, or including, the RO-labeled precursor. For example, an 8-armed PEG precursor of about 10 k Daltons, with 5 of the 8 arms terminating in SG and 3 of the 8 arms bound to triiodobenzoate (TIB) at a concentration of 2% gel solids will have about 0.18% iodine in the gel and 93 HU, compared to a 20% gel solids gel with 1.8% iodine in the gel and about 700 HU. 4-arm (Example 3).
King is made of record to illustrate that it is well known in the art to include initiator such as dicumyl peroxide capable of initiating a free radical polymerization reaction. Further discloses a hydrogel composition comprising water, a first crosslinked polymer, and a second crosslinked polymer, wherein the first crosslinked polymer comprises poly(ethylene oxide) and the second crosslinked polymer comprises a hydrophilic polymer other than poly(ethylene oxide), wherein the first crosslinked polymer and the second crosslinked polymer form an interpenetrating network (IPN). The hydrogel of the present invention has an attractive combination of water absorption and compressive strength. The hydrogel composition finds use as a drug delivery device. The invention also provides a method of preparing such hydrogel composition (abstract). The hydrogel composition has a water content less than about 70% or more by weight, for example, about 20% to about 60% by weight, about 25% to about 55% by weight, about 30% to about 50% by weight of the composition (0009). In one embodiment, a method for producing a hydrogel composition, the consolidated body further includes a free radical initiator, a peroxide initiator such as benzoyl peroxide or dicumyl peroxide (0031).
It would have been obvious to one of ordinary skill in the art at the time the invention made to incorporate initiators and co-initiators into Bright and Pathak’s hydrogel composition. The person of ordinary skill in the art would have been motivated to make those modifications because Campbell teaches that a initiator group is a chemical group capable of initiating a free radical polymerization reaction and used to initiate free radical crosslinking reactions at body temperatures to form hydrogel (0079) and reasonably would have expected success because reaction kinetics are generally controlled in light of the particular functional group, their concentrations, and the local pH unless an external initiator agent is required, in which triggering the initiator can be a controlling step (0087).
Conclusion
No claims are allowed at this time.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JAGADISHWAR RAO SAMALA whose telephone number is (571)272-9927. The examiner can normally be reached Monday-Friday 9am-6pm.
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/J.R.S/ Examiner, Art Unit 1618
/Michael G. Hartley/ Supervisory Patent Examiner, Art Unit 1618
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