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 .
Status of the Claims
Claims 5, 6, and 8-15 have been canceled. Claims 21-30 have been added. Accordingly, claims 1-4, 7, and 16-30 are pending and under current examination.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/29/25 has been considered by the examiner.
Withdrawn Rejections
All rejections of newly canceled claims are withdrawn.
In view of Applicant’s amendments, the following rejections are also withdrawn: the rejection of claims 1, 4, 6, 16, and 17 under 35 U.S.C. 103 as being unpatentable over Harari; the subsequent rejection of claims 2, 3, and 18 further in view of Chang; and the rejection of claims 5, 7, 19, and 20 further in view of Huang.
Response to Arguments
Applicant’s arguments filed 10/29/2025 (hereafter, “Remarks”) have been fully considered and are addressed as follows. The status of the claims and new claims are noted.
Regarding the previously issued rejections of claims 1, 4, 6, 16, and 17 as being unpatentable under 35 U.S.C. 103(a) over Harari, Applicant notes amendments to claim 1. Applicant argues that Chang does not cure Harari’s deficiency with regard to the concentration claimed. In reply, Applicant argues that the function of riboflavin in the prior art is different from the function of riboflavin in the instant claims and concludes that one cannot arrive at claim 1 over Harari and Chang without motivation and hindsight. In reply, Applicant’s argument has been considered but is not persuasive in view of what the combination of cited references reasonably suggests to the ordinary artisan and since the prior art may do what Applicant has done but for a different purpose and render obvious the claim.
Further regarding claims 4, 7, 19, and 20, Applicant notes the intensity range and asserts that Huang uses a light range for a different purpose than claimed and that Huang and the instant invention use different reaction mechanisms and reaction environments. In reply, first of all, the claim limitation pertaining to intensity is addressed below by the new grounds of rejection resulting from a combination of references and not Huang alone. Secondly, Applicant’s argument about different reaction mechanisms and environments is not persuasive since the claimed method steps appear to be taught by the processes in the prior art. Huang in particular teaches biomedical devices including catheters, balloons, and stents with functional layers which may include riboflavin desirably for the function and properties known of riboflavin. It is maintained that both Harari and Huang teach crosslinkers to provide desired functionality in medical devices and that Huang provides rationale for using crosslinkage via photopolymerization using riboflavin in Harari’s method of providing drug coating features including riboflavin. The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Applicant notes new claims and asserts they should be allowable by virtue of their dependencies. In reply, this argument is not persuasive in view of the new grounds of rejection necessitated by amendments as presented below.
New Ground of Rejection Necessitated by Amendments filed 10/29/2025
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.
Claims 1-4, 7, and 16-30 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 1 and 16 in the last two lines of each claim recite “wherein when the first reagent is in the form of a solution, the first reagent has a concentration in a range of 0.2 to 60 mg/mL based on total riboflavin”. The part and the whole referenced by the word “concentration” is unclear. From earlier in the claim it appears when the first reagent is in the form of a solution, riboflavin would be a part and a first reagent would be a whole such that mg/mL would refer to mg riboflavin per mL solution. However, “based on total riboflavin” is indefinite since whatever is “based on” would refer to a total amount. It is unclear whether a “total” riboflavin references a part of riboflavin per first reagent, a total riboflavin references a part of riboflavin per some sort of riboflavin solution referencing dissolved vs. undissolved riboflavin, or another part and whole concentration of riboflavin such as in a first reagent and out of said first reagent. The new hypothetical “wherein when” clause is wholly unclear as to what concentration part and whole is being claimed. Appropriate clarification is required.
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.
Claims 1-3, 16-18, 29, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over US 2018/0056086A1 (“Harari”) in view of US2016/0175408A1 (“Chang”).
The claims are drawn to a method comprising applying a first reagent comprising riboflavin and/or riboflavin salt to a predetermined location in a blood vessel; and applying light to the predetermined location to activate the riboflavin for an intended purpose newly recited in the claims, wherein when the first reagent is in the form of a solution, the first reagent has a concentration in a range of 0.2 to 60 mg/mL based on total riboflavin.
Regarding claims 1 and 16, pertaining to methods of generating a stent, using a catheter in claim 16, Harari teaches expansion of a balloon device (see [0045]) having a proximal end, a distal end, and a working length therebetween; an active agent; and a photoactivating light source. Harari also describes tubes (see [0065])(limitation of claim 29). The expandable member may be at least partially formed of a porous material, and a catheter allows an optical fiber capable of transmitting a laser radiation to pass through. The cross-linking agent comprises a riboflavin-containing photoactive substance, and the crosslinking agent is released into a vascular wall in a lumen for instance (“applying a first reagent comprising riboflavin to a predetermined location in a blood vessel” as in claim 1) thereby achieving at least some degree of the effect and/or intended use described in claim 30. Further regarding claim 16, Harari specifies that the device may include a catheter type device which includes at least one tube-shaped or hollow elongate body (see [0065]) which appears to function to have the balloon body fixed to a distal end and in communication with the tube body and functioning as a light-guiding element as further recited in the preamble of claim 16. Irradiation for photoactivation occurs immediately while releasing the crosslinking agent at an intervention site (“applying light to the predetermined location to activate… the first reagent,…” as in claim 1) wherein the light may be placed on an outer surface of the inflatable balloon and functioning such that the light source may activate the active agent in situ (see [0041]-[0047] and [0047] in particular)(limitations of claims 1, 16, and 17). Harari teaches methods for treating restenosis by changing a property of an extracellular matrix within a tissue surrounding a vascular stent for instance (see [0038]). This method takes place in a blood vessel (see [0040])(“to act on the predetermined location to generate the in-situ vascular stent” as in the last two lines of claim 1). As to claim 2, Harari describes a catheter may be used for supplying the cross-linking agent vascularly (see Harari claim 6), or it may be delivered via a layered coating (see Harari claim 3), a process which appears the same or substantially the same as a process producing the effects described in claim 30. Harari teaches light application as well as a light-guiding element and its stepwise method of use at least at [0067] and [0068] (limitation fo claim 16).
Because this rejection relies on combining various elements from Harari’s general disclosure into a single embodiment, this rejection is made using obviousness rationale. It is the examiner’s position that it would have been prima facie obvious to one of ordinary skill in the art to combine a method particularly for generating an in-situ vascular stent as claimed based on Harari’s teaching of riboflavin application into a similar type device (catheter/stent/tube), for in situ deployment to a stent using light application to cause generation of the device itself. Specifically, Harari teaches the treatment of a particular condition by changing a property of an extracellular matrix within a tissue surrounding a vascular stent and that crosslinking a collagen fibril of the extracellular matrix as induced by a photosensitizer provides this functionality (see [0038] and [0047] in particular). It would have been obvious to employ riboflavin as generally taught by Harari in a particular method of delivery as in Harari’s claim 31’s method, with a reasonable expectation of success. One would have been motivated to do so since Harari teaches riboflavin as a crosslinking agent which is photoactive and may be employed to facilitate stent generation (see Harari claims 10, 12, 13, and 16 in particular).
Regarding the new claim language wherein the intended function of performing the applying light step is now recited to be “for promoting binding of the riboflavin with collagen or other proteins on the blood vessel wall to generate the in-situ vascular stent on the predetermined location [in a blood vessel]”, since Harari teaches the structural features claimed including active steps of applying a first reagent and applying light as claimed, it appears Harari teaches a process inseparable from the intended results or effects instantly claimed. Moreover, Harari specifically teaches that riboflavin may be employed to facilitate stent generation (see Harari claims 10 and 13 in particular). Moreover and specifically regarding the new claim language naming riboflavin as an active ingredient and its intended function of promoting binding as further specified in the claims, where Harari teaches the same components and processes claimed, Harari is considered to teach the claimed properties and effects since a product and its properties are inseparable.
The teachings of Harari have been delineated above. Harari does not teach riboflavin concentration as in claims 1 and 16 as amended.
Chang teaches a method for delivery of certain formulations wherein a photoactive substance comprising riboflavin is included and may be treated with a photoactivating light having wavelength of about 300 to about 500 nm (see [0015], [0018], [0021]). The invention encompasses interventional operations for instance (see [0536]). Vitamins and minerals are among therapeutic agents which may be administered as supplements for instance (see [0285]-[0286]) with riboflavin in particular being named as important to cell metabolism and at times being administered by IV (see [0287]-[0288]). Chang specifies that where a container comprises a composition formulated for injection, the aqueous solution may comprise about 3.6 mg riboflavin salt in a volume of for instance about 3.6 mL (see [0039], [0040]), an example amount within the instantly claimed ranges recited in claims 1, 3, and 18. Chang teaches release upon inflation of the expandable member for a time for instance between 1 and 20 seconds (see [0073] and [0076] and that the light source is operated to photoactivate the crosslinking agent (i.e., riboflavin) (see [0074])(limitation of claim 4). Multiple pulses having a duration of 4 to 60 seconds may optionally be used to provide photoactivation by the light source wherein single pulses may have a duration also of 4 to 60 seconds (see Harari [0076]), a range overlapping the instantly claimed range of applying light in a range of 3 to 10 minutes as in claim 7; one would have been motivated to optimize the number of pulses and the duration of each in order to achieve the desired photoactivation results in accordance with Harari and Chang’s suggestion.
Both Harari and Chang are directed to riboflavin-containing formulations including those which may be administered for instance intravenously and/or by injection. It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to utilize a riboflavin concentration of approximately 1.0 mg/mL as suggested among the various examples calculated from Chang’s teachings, for the delivery of riboflavin in a formulation as generically taught by Harari, with a reasonable expectation of success. One would have been motivated to do so since Chang teaches a dosage amount formulated for injection in a particular packaged volume (see [0039] and [0040]).
Further regarding claim 17, Harari teaches drug eluting devices also including a balloon structure (see abstract, in particular). As to claim 18, Harari discloses the balloon surface may be functionally treated on the outer surface for instance (see [0043]).
Claims 4, 7, 19, and 20 are rejected under 35 U.S.C. 103 as being unpatentable over US 2018/0056086A1 (“Harari”) in view of US2016/0175408A1 (“Chang”) as applied to claims 1-3, 16-18, 29, and 30 above, and further in view of US20070082019A1 (“Huang”).
The teachings of Harari and Chang have been delineated above. Regarding claims 4 and 7, Harari teaches the photoactivating light to have a wavelength within the range of 300-500 nm (see Harari claim 17), a range entirely included by the range of 300 to 700 nm and further, Harari teaches a light source to be pulsed for instance for a duration of 4 to 60 seconds (see [0076]), a range within the recited 0.1 to 30 minutes.
Neither Harari nor Chang specifies light intensity or duration as in claims 4 and 7 and these limitations as repeated in claims 19 and 20. Huang cures this deficiency. Huang teaches a hydrogel layer applied to a substrate advantageously when the layer is formed in situ incorporating a photocrosslinkable moiety (see abstract, in particular). Huang encompasses the inclusion of riboflavin as a photoinitiator as an alternate embodiment (see [0115]) but more generally speaks to hydrogels which may be used as coatings and may employ a photoinitiator as is the state of the art (see [0004]). Huang teaches the state of the art to hydrogel materials for instance for use as coatings in catheters, catheter ballons, and stents (see [0002]). For instance, irradiation of substrate coatings may be done by a methodology for instance for 5 minutes with a near UV exposure such as 20 mW/cm2 at 365 nm for forming a hydrogel coating (see [0115]); these parameters overlap with the parameters recited in claims 5, 7, 19, and 20.
Harari and Huang are both directed to medical device type products comprising functional coatings for the purpose of providing particular medical application benefits such as drug delivery as in Harari or selective protein binding benefits as in Huang; both references employ crosslinkers in order to provide the desired functionality. It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to utilize Huang’s photocrosslinking stepwise method of light exposure parameters including wavelength range, intensity, and duration features in order to facilitate similar crosslinkage in the functional coatings taught by Harari, with a reasonable expectation of success. One would have been motivated to do so to ensure crosslinkage via photopholymerization using riboflavin as a photoinitiator, as suggested by Huang (see [0115]). Moreover, from Huang’s starting point, one would have been motivated to perform routine optimization procedures in order to achieve the desired drug coating deposition including riboflavin as in Harari, as is customary in the art.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over US 2018/0056086A1 (“Harari”) in view of US2016/0175408A1 (“Chang”) as applied to claims 1-3, 16-18, 29, and 30 above, and further in view of WO2014/022867A1 (Noddin et al.; hereafter “Noddin”).
The teachings of Harari and Chang have been delineated above. Neither of these specifies two balloon bodies as in claim 21. Noddin cures this deficiency.
Noddin teaches multi-balloon catheters with an optical diffuser element for treating vascular stenosis (see title and abstract, I nparitcular). There is a cathtershaft and a pair of occlusion balloons as well as adilation balloon with luman features spaced throughout the multi-balloon cather system as further dspecified and encompassing the tube body communication and blood flow capability further specified in the instant claim.
Harrari, Chang, and Noddin are all directed to balloon type functional medical devices. It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to employ the functionally coated medical devices as in Harari and Chang in a multi-balooon structure with optical eleements as taught by Noddin, with a reasonable expectation of success. One would have been motivated to do so to provide good balloon body positioning and communication and therefore controlled usage as taught by Noddin. One would have been motivated to do so to supply inflation fluid precisely as desired by Noddin for optimally controlled release in a vascular treatment method for instance.See also Noddin [0015] which further shows the overlapping steate of the art among all references relied upon.
Claim 22 is rejected under 35 U.S.C. 103 as being unpatentable over US 2018/0056086A1 (“Harari”) in view of US2016/0175408A1 (“Chang”) and US20070082019A1 (“Huang”) as applied to claims 1-4, 7, 16-20, 29, and 30 above, and further in view of JP2016154869A (translation enclosed, Lixiao Wang, hereafter “Wang”).
The aforementioned references do not teach the concentration of coating amount per unit surface area as in claim 22.
Wang cures this deficiency. Wang teaches a drug release coating for a medical device such as a balloon catheter wherein the balloon catheter includes a coating layer on the exterior surface of said balloon with a therapeutic agent,surfactant, and additional formulation components included in the coating (see abstract, in particular). Wang’s products encompass local drug delivery catheters, delivery balloon catheters, and polymeric drug coated stents (page 2 of translation, second paragraph). Wang recommends the concentration of a therapeutic agent to be added at about 1-20 micrograms per mm^2 and a weight ratio of therapeutic agent to additive to be about 0.5-100 so that the release of the drug is controlled.
Harari and Wang are both directed to drug-eluting devices which may comprise expnaable member or balloons coated with functional agents and capable of treating or preventing restenosis. It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to use Wang’s recommended amount of therapeutic agent as a starting point from which to perform routine optimization procedrues with regard to the functional agent amount to be included in a product of Harari, Chang, and Huang, with a reasonable expectation of success due to the very similar fields of endeavors and problem to solve. One would have been motivated to do so as routine inquiry in the art for achieving functional efficacy and stable formulation for use in a restenosis method of using a coated balloon product for instance.
Claims 23-28 are rejected under 35 U.S.C. 103 as being unpatentable over US 2018/0056086A1 (“Harari”) in view of US2016/0175408A1 (“Chang”) as applied to claims 1-3, 16-18, 29, and 20 above, and further in view of JP2016154869A (translation enclosed, Lixiao Wang, hereafter “Wang”).
The aforementioned references do not teach the carrier component as in claim 23; it is noted that claim 24 depends from claim 23.
Wang cures this deficiency. Wang teaches a drug release coating for a medical device such as a balloon catheter wherein the balloon catheter includes a coating layer on the exterior surface of said balloon with a therapeutic agent, surfactant, and additional formulation components included in the coating (see abstract, in particular). Wang’s products encompass local drug delivery catheters, delivery balloon catheters, and polymeric drug coated stents (page 2 of translation, second paragraph). Wang among additives that may be included discloses polyethylene glycol for instance (see last paragraph page 8/68 of translation)(limitation of claim 23) and the formulation may be an aqueous dilution or dispersion (see page 19/68)(water, limitation of claim 24) indicating a solvent comprising at least water. Wang teaches that the coating technique may be a spray technique for instance onto a balloon catheter (see paragraph starting “Various techniques for applying…” on page 24/68 of translation). Wang further teaches that the medical device may be sprayed with coating and then the solvent evaporates wherein an oven drying technique for instance may be employed (see page 25/68 of translation, paragraph 3) and that the order of steps may be varied as desired (see page 26/68, fifth full paragraph). Wang also teaches porous and perforated balloons for instance (see page 25/68, paragraph 6)(limitations of claims 25-27).
Harari and Wang are both directed to drug-eluting devices which may comprise expandable member or balloons coated with functional agents and capable of treating or preventing restenosis. It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed to use Wang’s recommended carrier and/or solvent components in a method of making a coating such as spray coating and subsequent solvent removal for a functional on a coated balloon medical device. One would have been motivated to do so based on Wang’s teaching of the state of the art with regard to functional catheters, balloons, and stent type products.
Conclusion
No claim is allowed.
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 AUDREA B CONIGLIO whose telephone number is (571)270-1336. The examiner can normally be reached Monday - Thursday 7:00 a.m. - 5:30 p.m..
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached at 5712720616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/AUDREA B CONIGLIO/ Primary Examiner, Art Unit 1617
Prosecution Insights