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 .
Summary
The amendment filed June 29, 2026 has been entered. Claims 1–4, 6–9, 17–19, and 21–29 are pending. Claims 5, 10–16, and 20 have been cancelled. Claims 1, 8, 24, 28 are currently amended.
Election/Restrictions
Applicant elects Group I without traverse, claims 1-4, 6-9, 24, and 27-29 drawn to an implantable medical device. Amendment of claim 24 to depend from claim 1 is appropriately included in Group I. Group II, claims 17-19, 21-23 and 25-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 1-4, 6-9, 24 and 27-29 are pending and under examination in this application. The election is made FINAL.
Priority
The current application filed on 09/09/2022 is a 371 of PCT/US2022/076230 filed 09/09/2022, which is a Continuation in Part of PCT/ US2022/076236 which in turn claims priority to provisional patent application 63/242,468 filed on 09/09/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 04/01/2026, 08/07/2025, 01/15/2025 and 03/07/2024 are in compliance with the provisions of 37 CFR 1.98. Accordingly, the information disclosure statements has been considered by the examiner. Signed copies have been attached to this office action.
Claim Rejections - 35 USC § 102
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 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.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Arditi (US 2003/0077279 A1).
Arditi teaches the treatment of atherosclerosis and other vascular diseases such as thrombosis, restenosis after angioplasty and/or stenting, and vein-graft disease after bypass surgery, by inhibition of the expression or biologic activity of Toll-like receptor-4 (TLR-4). Also included is an intravascular device coated with a compound that inhibits TLR-4; thereby imparting an improved efficacy to the device. TLR-4 cell signal transduction is at least partially responsible for the manifestation, continuation, and/or worsening of atherosclerosis and other forms of vascular disease. Furthermore, Arditi provides several means with which to inhibit this signal transduction pathway (abstract).
Regarding claim 1, Arditi discloses an implantable medical device — specifically an intravascular device selected from the group consisting of a catheter and a stent — comprising a therapeutic composition coated upon the intravascular device, wherein the device is exposed to a biological fluid when implanted in patients (Abstract; ¶ [0067]). Arditi explicitly teaches that the therapeutic composition comprises a TLR-4 inhibitor (¶ [0067]) (“a therapeutic composition coated upon the intravascular device, the therapeutic composition comprising a TLR-4 inhibitor”). Arditi further discloses that the TLR-4 inhibitor is an anti-TLR-4 antibody — specifically a neutralizing antibody specific for TLR-4 (claim 41 “the TLR-4 inhibitor is the anti-TLR-4 antibody”); ¶ [0020] (“an anti-TLR-4 antibody”). This anti-TLR-4 antibody constitutes a neutralizing antibody specific for TLR-4, thereby satisfying the biologically active agent limitation of claim 1 under alternative (i). Moreover, Arditi discloses a method of improving the efficacy of a catheter by coating the catheter surface with a composition comprising a TLR-4 inhibitor, specifically including methods used in stent coatings, by contacting the surface of the catheter with the composition (claims 1–2). With respect to cellular attachment, Arditi’s catheter surface coated with a neutralizing antibody specific for TLR-4 is capable of decreasing cellular attachment to the catheter surface (¶¶ 0050-0054), as a recitation of intended use must result in a structural difference to distinguish the claimed invention, and Arditi’s structure inherently meets this functional limitation. See MPEP § 2114. Accordingly, Arditi discloses each and every limitation of claim 1.
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 1-4, 6-9, 24 and 27-29 are rejected under 35 U.S.C. 103 as being unpatentable over Arditi (US 2003/0077279 A1) in view of Chudzik (US 2002/0032434 A1) and further in view of Serhan (US 2006/0019875 A1) and/or Evans (WO 2020/237325 A1) and further in view of evidentiary reference Neal “Discovery and Validation of a New Class of Small MoleculeToll-LikeReceptor4(TLR4) Inhibitors.
Chudzik teaches a coating composition for use in coating implantable medical devices to improve their ability to release bioactive agents in Vivo. The coating composition is particularly adapted for use with devices that undergo significant flexion and/or expansion in the course of their delivery and/or use, such as stents and catheters. The composition includes the bioactive agent in combination with a mixture of a first polymer component Such as poly(butyl methacrylate) and a second polymer component such as poly(ethylene-co-Vinyl acetate) (abstract).
Serhan teaches a hydrocephalus shunt having an anti-inflammatory coating applied to at least the outside surface of the ventricular catheter. Such coatings are also applicable to other medical devices or implants (abstract).
Evans teaches compositions, devices and methods for treating neuroinflammatory conditions in female subjects. In certain embodiments, the present disclosure provides a method of treating a female subject suffering from, or susceptible to, a neuroinflammatory condition, the method comprising intrauterine administration to the subject of an effective amount of an agent that reduces activation of the innate immune system and thereby treating the subject (abstract).
Regarding claim 1, Arditi’s teachings are noted above in the 102 rejection. Accordingly, Arditi discloses each and every limitation of claim 1.
Regarding claims 2 and 3, claim 2 depends from claim 1 and further recites that the medical device releases the biologically active agent in an amount effective to reduce or inhibit astrocyte and/or glia cell deposition associated with the medical device, and wherein the medical device comprises 0.1 μg to 1 mg of biologically active agent per mm² of surface area of the portion of the medical device to which the biologically active agent is applied or incorporated. Arditi, as applied to claim 1, discloses the base device. Arditi does not explicitly recite the 0.1 μg to 1 mg/mm² dosage range limitation or the astrocyte/glia cell deposition reduction limitation in those terms. Chudzik discloses a medical implant that releases a biologically active agent in an amount effective when implanted in vivo, wherein the medical implant comprises 0.1 μg to 1 mg of biologically active agent per mm² of surface area of the portion of the medical implant to which the biologically active agent is applied or incorporated (¶ [0013]; ¶ [0030] (the weight of the coating attributable to the bioactive agent is preferably in the range of about 0.05 mg to about 10 mg of bioactive agent per cm² of the gross surface area; more preferably, between about 1 mg and about 5 mg per cm²). Chudzik is in the field of coating implantable medical devices with bioactive agents in controlled amounts to achieve a therapeutic effect in vivo.
Prima Facie Obviousness and Motivation to Combine: It would have been obvious to a person of ordinary skill in the art at the time of the invention to incorporate the controlled bioactive agent loading taught by Chudzik into the Arditi device. Both references are in the same field of implantable medical device coatings incorporating biologically active agents. A person of ordinary skill would have been motivated to apply Chudzik’s established dosage engineering framework to the Arditi TLR-4 antibody coating because controlling the amount of biologically active agent per unit surface area is a routine and recognized design parameter for achieving consistent therapeutic efficacy from a coated medical device (¶ [0013]; ¶ [0030]). The combination would predictably result in an Arditi-type device with optimized agent loading within Chudzik’s disclosed and clinically informed range. With respect to the astrocyte/glia deposition limitation, as noted above with respect to claim 1, this is a recitation of intended use or a functional property that follows inherently from the anti-TLR-4 antibody coating — a coating that by its nature reduces the TLR-4-mediated inflammatory cascade responsible for astrocyte and glia cell recruitment and deposition. No structural difference is created by the recitation of this functional result. See MPEP § 2114.
The combination of Arditi and Chudzik renders claim 2 prima facie obvious.
Claim 3 depends from claim 2 and further recites that the medical device further comprises one or more of a tube, a chronic indwelling central nervous system (CNS) catheter, a neurological or neurosurgical device, a central nervous shunt, a pump, or a catheter. Arditi discloses that the intravascular device is selected from the group consisting of a catheter and a stent (¶ [0067]; Claim 1). Arditi further discloses that the methods of the invention may be used in a range of implantable and indwelling devices (Abstract). Chudzik further discloses that the coating composition is particularly adapted for use with devices that undergo significant flexion and/or expansion, including catheters (Abstract; ¶ [0030]). Moreover, Serhan specifically demonstrates CNS shunts and ventricular catheters suffering inflammatory obstruction, providing motivation to apply Arditi’s anti-inflammatory coating to these known CNS devices.
Motivation to Combine: A person of ordinary skill would have found it obvious to apply the combined Arditi/Chudzik/Serhan device coating to a CNS catheter or central nervous shunt, given that the explicit motivation of the claimed invention — prevention of astrocyte and glial deposition — is most clinically relevant in CNS indwelling devices such as ventricular shunts and CNS catheters. Selecting from among known implantable device types for application of a known anti-inflammatory coating involves only routine engineering judgment and offers predictable results. See KSR Int’l Co. v. Teleflex Inc., 550 U.S. 398 (2007). The combination renders claim 3 prima facie obvious.
Regarding claims 4 and 27, claim 4 depends from claim 1 and recites that the medical device comprises GIT 27 or another TLR-4 inhibitor as the biologically active agent. Arditi discloses a neutralizing antibody specific for TLR-4 as a TLR-4 inhibitor. See Arditi, at (claim 41; ¶ [0020]) further discloses a broad class of TLR-4 inhibitors as candidate biologically active agents for the device coating and teaches that various small molecule inhibitors of TLR-4 signaling may be used (¶¶ [0019]–[0021]). GIT 27 (also known as 4,5-dihydro-3-phenyl-5-isoxazoleacetic acid) is a known TLR-4 inhibitor known in the art as of the priority date as evident by Neal “Discovery and Validation of a New Class of Small MoleculeToll-LikeReceptor4(TLR4) Inhibitors”.
Motivation to Combine / Prima Facie Obviousness: To the extent GIT 27 is not explicitly named in Arditi, it represents a specific, well-known member of the class of TLR-4 inhibitors expressly taught by Arditi. Selection of GIT 27 from among the known TLR-4 inhibitors taught by Arditi would have been an obvious design choice to a person of ordinary skill, representing nothing more than the routine substitution of one known TLR-4 inhibitor for another within a recognized class. See KSR, 550 U.S. at 416 (“obvious to try” where there is a finite number of identified, predictable solutions).
Claim 27 depends from claim 1 and recites that the medical device is a ventricular shunt. Arditi discloses implantable medical devices including catheters and stents adapted for indwelling use (Abstract; ¶ [0067]). It would have been obvious to apply the known anti-inflammatory coating in a ventricular shunt because ventricular shunts are a recognized class of implantable CNS catheters subject to inflammatory obstruction, and Serhan teaches using anti-inflammatory coatings on such devices to address that know problem.
Regarding claims 6, the claim depends from claim 1 and recites that the inhibitor of production or activity of TNF-α comprises one or more of: a neutralizing antibody specific for TNF-α, etanercept, infliximab, adalimumab, certolizumab pegol, or golimumab. Arditi provides the base device with a TLR-4 inhibitor coating. Arditi further broadly teaches that inhibitors of pro-inflammatory cytokines including TNF-α may be used (¶¶ [0019]–[0021]). Serhan discloses a hydrocephalus shunt system with an anti-inflammatory coating and teaches use of anti-inflammatory compositions including compounds that reduce TNF-α activity (¶ [0047]) (adiponectin suppresses TNF-α). Etanercept, infliximab, adalimumab, certolizumab pegol, and golimumab are all established anti-TNF-α biologics well known in the pharmaceutical arts as of the priority date. Motivation to Combine: A person of ordinary skill would have been motivated to select any of the named TNF-α inhibitors for the Arditi device because each is a known anti-TNF-α agent whose mechanism of action — specifically inhibiting TNF-α production or activity — is squarely taught by both Arditi and Serhan as desirable for anti-inflammatory device coatings. The selection involves only routine substitution within a well-characterized class of agents with predictable results.
Regarding claim 7, the claim depends from claim 1 and recites that the inhibitor of production or activity of IL-1α or IL-1β comprises one or more of: a neutralizing antibody for IL-1, a neutralizing antibody specific for IL-1α, a neutralizing antibody specific for IL-1β, anakinra, Rilonacept, or canakinumab. Arditi teaches a device coating comprising an inhibitor of IL-1β production or activity ([0021]). Anakinra (recombinant IL-1Ra), Rilonacept (IL-1 trap), and canakinumab (anti-IL-1β monoclonal antibody) are all well-established agents as known IL-1 pathway inhibitors prior to the effective filing date.
Motivation to Combine: A person of ordinary skill would have been motivated to apply any of these known IL-1 pathway inhibitors in the Arditi device context, as each is a validated agent acting on the IL-1 signaling pathway that Arditi explicitly identifies as a target. Selection among established IL-1 inhibitors for coating a medical device is a routine exercise involving no more than ordinary skill and predictable outcomes.
Regarding claim 8, the claim depends from claim 1 and recites that the inhibitor of production or activity of TLR-4 comprises one or more of: a neutralizing antibody of TLR-4, GIT 27, Eritoran, ibudilast, NI-0101, 1A6, or 15C1. Arditi discloses anti-TLR-4 antibody as a TLR-4 inhibitor (claim 41; ¶ [0020]). Eritoran (E5564), ibudilast, NI-0101, 1A6, and 15C1 are all recognized TLR-4 inhibitors in the art as of the priority date.
Motivation to Combine: Selection of any named TLR-4 inhibitor from among established members of the class would have been obvious to one of ordinary skill, as all are known agents acting on the same TLR-4 pathway that Arditi identifies as the therapeutic target. No unexpected results distinguish these specific agents from the class taught by Arditi.
Regarding claim 9, the claim depends from claim 1 and recites that the inhibitor of production of IL-6 comprises one or more of: Tocilizumab, Sarilumab, Clazakizumab, Olokizumab, ALX-006, or 116-25. Arditi teaches use of an inhibitor of IL-6 production or activity as a biologically active agent for the device coating (¶ [0021]). Tocilizumab (anti-IL-6R mAb), Sarilumab, Clazakizumab, and Olokizumab are all anti-IL-6 pathway agents recognized in the art prior to the priority date. Motivation to Combine / Prima Facie Obviousness: Selection of established IL-6 pathway inhibitors for a device coating targeting IL-6, as taught by Arditi, would have been obvious to one of ordinary skill. Each named agent is a known anti-IL-6 or anti-IL-6R biologic; substituting any of them into the Arditi device context is routine and produces predictable results.
Regarding claim 18, Arditi discloses a method of coating the catheter with a TLR-4 inhibitor composition before implantation (Abstract; Claims 1–2 (coating applied before the device is implanted in the patient). Pre-installation coating is the standard delivery method taught by Arditi.
Regarding claim 19, Serhan discloses contacting the shunt with an anti-inflammatory composition before or after installation of the shunt in the patient (claims 36–37 (“the coating is sprayed upon the implant before implantation… the coating is sprayed upon the implant after implantation”); ¶ [0100]). The timing variation (before vs. during/after installation) is expressly disclosed by Serhan.
Regarding claim 24, Serhan discloses that obstruction results from inflammatory cells including astrocytes, and teaches contacting the shunt with an anti-inflammatory composition to inhibit such obstruction (¶ [0020] - ¶ [0030]). Evans more specifically teaches use of a neutralizing antibody specific for TLR-4 to inhibit astrocyte and/or glia cell activation (claims 1-15, 24-23, 31–38; ¶ [00197] - ¶ [00198]). The combination of Arditi’s anti-TLR-4 antibody method with Serhan and Evans’s teaching that such inhibition decreases astrocyte activation renders this limitation obvious.
Regarding claim 28, Arditi broadly teaches multi-cytokine targeting and the use of neutralizing antibodies against TNF-α and IL-6 as biologically active coating agents (¶ [0060] - (¶ [0071]). Including a second neutralizing antibody against IL-6 or TNF-α alongside a TLR-4 antibody is an obvious combination of known elements with predictable results.
Regarding claim 29, the claim depends from claim 3 and recites that the coating is applied to one or more of the tube, CNS catheter, neurological or neurosurgical device, central nervous shunt, pump, or catheter. This limitation is already subsumed by the device type analysis in claim 3. The coating of any of the recited device types is obvious for the reasons set forth above with respect to claim 3.
Response to Arguments/Amendments
The amendment filed June 29, 2026 has been entered and considered. The amendment to claim 24 to depend from elected claim 1 has been accepted and claim 24 has been examined as part of the elected invention. The election of Group I without traverse is acknowledged and made final. Applicant’s request for rejoinder of the nonelected process claims has been considered. In accordance with MPEP § 821.04(a), rejoinder will be considered if the elected product claims are subsequently found allowable. At present, because the elected product claims remain unallowable for the reasons set forth in this Office Action, rejoinder of the withdrawn process claims is not appropriate.
Applicant did not present substantive arguments directed to patentability. The amendments have been fully considered but do not overcome the rejections set forth in this Office Action.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ANDRE MACH whose telephone number is (571)272-2755. The examiner can normally be reached 0800 - 1700 M-F.
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/ANDRE MACH/Examiner, Art Unit 1615
/Robert A Wax/Supervisory Patent Examiner, Art Unit 1615
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