DETAILED ACTION
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 .
Receipt is acknowledged of Applicant’s Amendments and Arguments filed on 07/28/2026.
Claims 1, 10, and 17 have been amended.
Claims 11, 16 and 20-26 have been cancelled.
Claims 38-49 have been newly added. Accordingly, claims 1-10, 12-15, 17-19 and 27-49 are pending and presented for examination.
Any previous rejections and/or objections not reiterated herein have been withdrawn in view of amendments filed on 07/28/2026. The following rejections and/or objections constitute the complete set presently being applied to the instant application. However, upon further consideration new grounds of rejection is prepared as follow.
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) 1-10, 12-15, 17-19, and 27-49 are rejected under 35 U.S.C. 103 as being unpatentable over Bright (US 2016/0317621) in view of Pathak et al. (US 20060147409).
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). In another embodiment, the PEG precursor is a higher molecular weight 31.5 kDa N-hydroxysuccinimide end capped PEG, with the same buffer and trilysine acetate buffer, which together form a gel in about 10 seconds (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, disclose 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). In one embodiment the neurolytic agent (therapeutic agent) is co-administered 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). The gel could include a biodegradable or bioerodable polymer such as polylactic acid (D-, L-, D/L, PLA), polyglycolic acid (PGA), polylactic-co-glycolic acid (PLGA), polyaminoacids, poly(ethylene oxide), polyethylene glycol (PEG), poly(2-hydroxyethyl methacrylate) (PHEMA), and polyN-(2-hydroxypropyl)-methacrylamide (PHPMA), poly(methylmethacrylate) (PMMA) thereof. These polymers can be further modified to create hydrogels with cholesterol methacrylate or 2-ethoxyethyl methacrylate (EOEMA) (0399). 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 eliminate pain and unpleasant sensations during the procedure. (0472).
Bright fails to disclose protonated amine functional groups, hydrogel precursor solution has pH 4.0 to 6.2, visualization agent and polymerizable groups such as acrylate and methyacrylate functional groups in the hydrogel composition.
Pathak teaches hydrogel composition for delivery of drugs, prevention of post-operative adhesions, coating medical devices/vascular grafts, wound dressing and surgical sealants and the composition comprises precursors having electrophilic and nucleophilic functional groups. Visualization agents may be included with the crosslinked polymers (abstract). Preferred electrophilic functional groups are NHS, SNHS and ENHS (FIG. 9). In one embodiment, a colored visualization agent is added to the hydrogel precursors before crosslinking. The visualization agent is preferably an agent that provides a color that is visible to the human eye, e.g., a color that is detected visually by the user or detected by a video camera and relayed to a video screen observed by the user (0038). Preferred nucleophilic functional groups are primary amines. The advantage of the NHS-amine reaction is that the reaction kinetics lead to quick gelation usually within 10 about minutes, more usually within about 1 minute and most usually within about 10 seconds. This fast gelation is preferred for in situ reactions on live tissue. (0115). A four arm PEG with succinimidyl glutarate (SG) end groups was dissolved in 0.01M pH 4.0 phosphate buffer (reads on hydrogel precursor solution has a pH 4.0 to 6.2) and tri-lysine or tetra-lysine (reads on amine functional groups protonated) (0178). Aqueous solutions of NHS based crosslinkers and functional polymers preferably are made just before the crosslinking reaction due to reaction of NHS groups with water. Longer "pot life" may be obtained by keeping these solutions at lower pH (pH 4-5) (0118). The NHS-amine crosslinking reaction may be carried out in aqueous solutions and in the presence of buffers. The preferred buffers are phosphate buffer (pH 5.0-7.5). triethanolamine buffer (pH 7.5-9.0) and borate buffer (pH 9.0-12) (reads on activator solution) and sodium bicarbonate buffer (pH 9.0-10.0) (0117). Pathak discloses that the crosslinking density may be controlled by the overall percent solids of the crosslinker and functional polymer solutions. In one embodiment discloses four arm PEG with SG end groups (Shearwater Polymers, approx. 9,100 g/mol, 0.704 grams, 6.5 times10-5 moles) was dissolved in 2.96 g 0.01M pH 4.0 phosphate buffer (19.2% solids). Di-lysine (Sigma, 347.3 g/mol, 0.03 grams, 8.7 times10-5 moles) was dissolved in 3.64 grams of 0.1M pH 9.5 borate buffer (0.8% solids). On combination of the two solutions, the percent solids was 10%. The data from various formulations shows that the higher percent solids solutions also are the most stable with respect to retention of speed of reaction (01777 and 0183). Additional disclosure includes water soluble, branched or graft crosslinker or functional polymers with terminal amines, carboxylic acids or thiols functional groups include random copolymer of PEG-monoacrylate and some other acrylate or combination of acrylates, such that the final polyacrylate is water soluble. In the final step the acrylate is reacted with lysine using an appropriate quantity to achieve the desired degree of amination.
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 a hydrogel for use on a patient’s tissue has water, a biocompatible visualization agent, and crosslinked hydrophilic polymers and reactive precursor species with two to ten nucleophilic functional groups each and reactive precursor species with two to ten electrophilic functional groups each (0046). 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 PEG with succinimidyl glutarate (SG) end groups was dissolved in 0.01M pH 4.0 phosphate buffer and tri-lysine or tetra-lysine (reads on amine functional groups protonated in presence of buffer and hydrogel precursor solution has a pH 4.0 to 6.2), visualization agent and acrylate functional groups into Bright’s composition. The person of ordinary skill in the art would have been motivated to make those modifications because Pathak teaches that a visualization agent in the hydrogel makes the hydrogel change in its appearance until the user determines that the thickness of the hydrogel is sufficient. For example, a blue dye in the hydrogel makes the hydrogel increasingly opaque as the thickness of the hydrogel increases and thus, the visualization agent allows the user to ascertain the presence of the hydrogel on the surface and also gain feedback on the appropriate thickness, preferably in combination with instructions provided as part of a kit (0041 and 0048) and reasonably would have expected success because visualization agents improve their visibility during surgical procedures , especially useful when used in MIS procedures, due among other reasons to their improved visibility on a color monitor.
Conclusion
No claims are allowed at this time.
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). 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 (37 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 JAGADISHWAR RAO SAMALA whose telephone number is (571)272-9525. 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
