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 Claims
Receipt of Remarks/Amendments filed on 05/26/2026 is acknowledged. Claims 1 and 21 are amended and claims 2-5 are canceled. Claims 22-23 are new. Claims 1 and 6-23 are currently pending and are examined on the merits herein.
Priority
The instant application filed 02/22/2023, claims benefit to Provisional Application No. 63/396,052, filed 08/08/2022, Provisional Application No. 63/312,516, filed 02/22/2022, and Provisional Application No. 63/312,628, filed 02/22/2022.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 03/06/2026, 05/18/2026 (2), 05/26/2026, and 06/30/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
The following grounds of rejection are necessitated by amendment:
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 and 9-23 are rejected under 35 U.S.C. 103 as being unpatentable over Kite, P., et al. (US 8541472 B2, 09/24/2013, on record), hereinafter Kite, in view of Winnicki, W., et al. (2018). Taurolidine-based catheter lock regimen significantly reduces overall costs, infection, and dysfunction rates of tunneled hemodialysis catheters, Kidney International, Volume 93, Issue 3, Pages 753-760, (on record), hereinafter Winnicki.
Kite discloses antiseptic compositions comprising at least one salt of EDTA (abstract). The antiseptic have numerous applications, including applications as lock and lock flush solutions for various types of catheters (col. 6, lines 14-17; col. 7, lines 15-25; claims).
Regarding claims 1 and 21: Kite discloses EDTA solutions in a sterile and non-pyrogenic form (col. 11, lines 36-27, claim 1). The compositions comprise at least 1% of EDTA salt(s) by weight per volume of solution (w/v) and may comprise up to 15% (w/v) EDTA salt(s) (col. 9, lines 1-5), thereby reading on the instantly claimed range of 1-15% (w/v) EDTA. The antiseptic compositions comprise a sodium EDTA salt (or combination of sodium EDTA salts) in solution at a pH higher than physiological, preferably at a pH of >8.0, for example in a range of between 9.5 and 11.5 (col. 9, lines 47-57). For antiseptic compositions comprising sodium EDTA salt(s), and at the desired pH ranges (specified above), the sodium EDTA salts are predominantly present in both the tri-sodium and tetra-sodium salt forms (col. 9, lines 63-67).
Regarding claims 9 and 10: EDTA salt compositions may be formulated in a mixture of water and ethanol. Such solutions are highly efficacious. Ethanol concentrations of from more than about 0.5% and less than about 10%, v/v, provide effective antiseptic compositions (col. 11, lines 4-21). Kite specifically teaches a 2 mg/ml tetra-EDTA in 1% alcohol (ethanol) solution to provide excellent results (Ex. 6; col. 25, lines 45-47). Such amounts of ethanol fall within the instantly claimed range of 0.1-70% (w/v) ethanol.
Regarding claims 13 and 14: Exemplary compositions comprise 3.6-4.4% (w/v) EDTA salt(s) in aqueous solution (col. 9, lines 12-13), which falls within the instantly claimed ranges of 1-10% and 1-5% (w/v) EDTA.
Traditionally, catheters have been locked with normal saline or heparin solutions, which provide anticoagulant activity. While heparin has anticoagulant activity, it does not function as an antimicrobial and does not prevent or ameliorate infections (col. 2, lines 45-53). Catheter locking solutions comprising Taurolidine are also known (col. 2, lines 58-59).
The antiseptic compositions of Kite may contain materials, including active components, in addition to the EDTA salts described above. Other antimicrobial or biocidal components may be incorporated, although the use of traditional antibiotics and biocidal agents is generally discouraged as a consequence of the dire consequences of the development of antibiotic- and biocidal-resistant organisms (col. 10, lines 43-53).
The teachings of Kite differ from that of the instant invention in that Kite does not teach a specific embodiment comprising an additional ingredient selected from the group consisting of heparin, taurolidine, a thrombolytic agent, or a combination thereof as recited in claim 1 and further defined in claims 11-12 and 15-20 nor a thrombolytic agent alone as recited in claim 21.
Winnicki relates to a prospective, multicenter, randomized, controlled trial that compares two lock regimens using three commercial catheter lock solutions. In the taurolidine group, TauroLockTM-Hep500 was used twice per week and TauroLockTM-U25,000 once a week. Results indicated that use of taurolidine-based catheter lock solutions containing heparin and urokinase significantly reduced complications related to tunneled hemodialysis catheters when compared to four percent citrate solution and was overall more cost-efficient (abstract). The commercial catheter lock solutions in the taurolidine group were: TauroLock-Hep500 (1.35% taurolidine, 4% citrate, and 500 IU/ml heparin) and TauroLock-U25,000 (1.35% taurolidine, 4% citrate, and 25,000 IU urokinase) (p. 758, Catheter lock procedure). Taurolidine, a broad-spectrum, antimicrobial, nontoxic agent that reduces the development of biofilm is a nonantibiotic lock alternative that does not cause bacterial resistance and has no adverse effects, even if it leaks into circulation. Taurolidine reads on the additional ingredient of claims 1, 19, and 20. Furthermore, the addition of heparin to taurolidine–citrate has been shown to strengthen its efficiency regarding patency (p. 754, col. 1, para. 2). Heparin reads on the additional ingredient of claims 1, 11, and 12. The prophylactic use of urokinase or alteplase is considered in catheter lock solutions (CLSs) to prevent line occlusion (p. 753, col. 2, para. 3). There also seems to be an effect of fibrinolytics, such as urokinase and alteplase, on the reduction of catheter-related infections (CRIs) (p. 755, col. 1, para. 3). Urokinase and alteplase read on the additional ingredient (i.e., thrombolytic agent) of claims 1, 15-18, and 21.
Regarding taurolidine as the additional ingredient, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to incorporate 1.35% taurolidine into the solution of Kite since 1.35% taurolidine is known and effective in catheter lock solutions as taught by Winnicki. One of ordinary skill in the art could have combined the known taurolidine of Winnicki with the known lock solutions of Kite according to known methods to predictably yield the instant invention, as motivated by taurolidine’s broad-spectrum, antimicrobial, nontoxic properties that reduce the development of biofilm.
Regarding heparin as the additional ingredient, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to incorporate 500 IU/ml of heparin into the solution of Kite since 500 IU/ml of heparin is known and effective in catheter lock solutions as taught by Winnicki. One of ordinary skill in the art could have combined the known heparin of Winnicki with the known lock solutions of Kite according to known methods to predictably yield the instant invention, as motivated by heparin’s anticoagulant activity and ability to improve patency.
Regarding a thrombolytic agent as the additional ingredient, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to incorporate 25,000 IU of urokinase (i.e., a thrombolytic agent) into the solution of Kite since 25,000 IU of urokinase is known and effective in catheter lock solutions as taught by Winnicki. One of ordinary skill in the art could have combined the known thrombolytic agents of Winnicki with the known lock solutions of Kite according to known methods to predictably yield the instant invention, as motivated by urokinase’s ability to prevent line occlusion and help reduce catheter-related infections.
Regarding claims 11 and 12, the combination of Kite and Winnicki teaches wherein the additional ingredient comprises heparin as discussed above. However, the references do not explicitly teach the concentration of heparin in terms of a (w/v) percent. The combined teachings make obvious the inclusion of 500 IU/ml of heparin. Given this teaching, one of ordinary skill in the art could have determined the appropriate amount of heparin to include in the combined catheter lock solution through no more than routine experimentation based on the desired activity of heparin in the final solution. 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). Thus, the claimed concentration of heparin in instant claims 11-12 would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claims 17 and 18, the combination of Kite and Winnicki teaches wherein the additional ingredient comprises urokinase as discussed above. However, the references do not explicitly teach the concentration of urokinase in terms of a (w/v) percent. The combined teachings make obvious the inclusion of 25,000 IU of urokinase. Given this teaching, one of ordinary skill in the art could have determined the appropriate amount of urokinase to include in the combined catheter lock solution through no more than routine experimentation based on the desired activity of urokinase in the final solution. 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). Thus, the claimed concentration of urokinase in instant claims 17-18 would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claims 19 and 20, the combination of Kite and Winnicki teaches wherein the additional ingredient comprises taurolidine as discussed above. The concentration of taurolidine made obvious is 1.35%, which falls within the instantly claimed ranges (i.e., 1-8% and 1-4%).
One of ordinary skill in the art would have had a reasonable expectation of success in making the above modifications since Kite welcomes additional actives so long as they don’t include traditional antibiotics and biocidal agents that result in undesired resistance. Taurolidine, the only antimicrobial discussed above, is a nonantibiotic lock alternative that does not cause bacterial resistance as taught by Winnicki. Furthermore both Kite and Winnicki teach compositions and active useful for catheter lock solutions.
Regarding claims 22 and 23, because the compositions made obvious by the prior art above are identical to the composition of claims 1 and 21, the compositions must necessarily have the characteristics claimed as an inherent property. It is noted that In re Best (195 USPQ 430) and In re Fitzgerald (205 USPQ 594) discuss the support of rejections wherein the prior art discloses subject matter, which there is reason to believe inherently includes functions that are newly cited, or is identical to a product instantly claimed. In such a situation the burden is shifted to the applicants to “prove that subject matter to be shown in the prior art does not possess the characteristic relied on” (205 USPQ 594). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of invention, but only that the subject matter is in fact inherent in the prior art reference.
Claims 1 and 6-23 are rejected under 35 U.S.C. 103 as being unpatentable over Kite and Winnicki as applied to claims 1 and 9-23 above, and further in view of Hoang, M. Q. S., et al. (US 2007/0202177 A1, 08/30/2007, IDS dated 02/20/2024), hereinafter Hoang, as evidenced by Prosl, F., et al. (US 6350251 B1, 02/26/2002, IDS dated 01/26/2026), hereinafter Prosl.
The combined teachings of Kite and Winnicki are discussed above.
The combined teachings of Kite and Winnicki differ from that of the instantly claimed invention in that neither explicitly teach wherein the composition further comprises chlorhexidine or a pharmaceutically acceptable salt thereof as recited in claim 6, nor the specific concentrations of chlorhexidine as defined in claims 7 and 8.
Hoang teaches antimicrobial compositions for use in locking catheters and other devices. The composition includes at least one alcohol and at least one biocidal agent which is not an alcohol (abstract). Especially preferred biocides include chlorhexidine gluconate, chlorhexidine acetate, and chlorhexidine diacetate ([0036]; claims 7-8), which read on the chlorhexidine of claim 6. The one or more biocidal agents are present in an amount of about 0.01-10 wt. % or about 0.01-5 wt. %, based on the total weight of the antimicrobial composition ([0036]; claim 9). Specific examples of the invention are shown in table 3. Formulations 4-7 and 10 comprise ethanol, EDTA, and chlorhexidine gluconate ranging from 0.25 to 2.5 wt. % (Table 3). Chlorhexidine is an example of non-antibiotic biocide as evidenced by Prosl (col. 18, lines 15-36; col. 5, lines 25-29). Non-antibiotic biocides are defined by Prosl to minimize the probability of producing microorganisms that are genetically immune thereto (col. 17, lines 46-55).
Thus, it would have been prima facie obvious to one of ordinary skill in the art, prior to the effective filing date of the claimed invention, to incorporate chlorhexidine into the solution of Kite and Winnicki since chlorhexidine is known and effective in catheter lock solutions as taught by Hoang. One of ordinary skill in the art would have been motivated to add the chlorhexidine of Hoang into the combined solution in order to increase its antimicrobial activity. Moreover, it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose (i.e., as a catheter lock solution), in order to form a third composition to be used for the very same purpose…[T]he idea of combining them flows logically from their having been individually taught in the prior art. In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Regarding claims 7-8, Hoang does not explicitly teach the concentration of chlorhexidine as a w/v % or in μg/ml. Hoang generally teaches that the biocidal agent may be present in an amount of about 0.01-10 wt. % or about 0.01-5 wt. %, specifically 0.25-2.5 wt. % in the case of chlorhexidine gluconate. Given these teachings, one of ordinary skill in the art could have determined the appropriate amount of chlorhexidine to include in the combined catheter lock solution through no more than routine experimentation based on the desired antimicrobial activity of chlorhexidine in the final solution. 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). Thus, the claimed concentrations of chlorhexidine in instant claims 7-8 would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention.
One of ordinary skill in the art would have had a reasonable expectation of success in incorporating chlorhexidine into the combined composition since chlorhexidine may be used in antimicrobial solutions comprising EDTA and ethanol similar to the combined composition of Kite and Winnicki. Additionally, Kite welcomes other actives so long as they don’t include traditional antibiotics and biocidal agents that result in undesired resistance. Chlorhexidine is a non-antibiotic biocide with minimized risk of resistance as evidenced by Prosl above.
Response to Arguments
Applicant's arguments filed 05/26/2026 have been fully considered but they are not persuasive:
(1) Applicant argues that nothing in Winnicki teaches or suggests a composition comprising heparin, taurolidine, a thrombolytic agent or a combination thereof having a pH from 9.5-11.5 and that the compositions of Winnicki are at or near a physiological pH.
In response to this argument, Winnicki is not relied on for teaching the instantly claimed pH. A pH of 9.5 to 11.5 is explicitly taught by the primary reference of Kite. Winnicki is relied on for teaching additional active ingredients that one of ordinary skill would be motivated to include for the various reasons stated above. One of ordinary skill in the art would have understood how to incorporate these additional ingredients while maintaining the desired high pH taught by Kite.
(2) Applicant argues that the proposed combination of the compositions of Kite and Winnicki amounts to no more than an assertion that the compositions could be combined, but there is no teaching or suggestion in the cited art that such a combination would result in an active or stable composition. Applicant argues that combining the compositions of Kite would lower the pH of the EDTA and affect the stability of the tetrasodium salt of EDTA and that there is no teaching or suggestion to modify the pH of the compositions of Winnicki to have a pH of 9.5-11.5 nor a reasonable expectation of success.
In response to this argument, Kite and Winnicki both teach known and effective catheter lock solutions. While there is not an explicit teaching that combining their active agents would provide an active or stable composition, there is also no explicit teaching that they would not form an active or stable composition (i.e., neither reference teaches against the other). The fact that Kite welcomes the addition of other active components and Winnicki teaches other known and routine catheter lock actives is enough to give one of ordinary skill in the art a reasonable expectation of success in combining them. An absolute expectation of success is not required. Furthermore, one of ordinary skill in the art would have recognized how to add in the active ingredients of Winnicki while maintaining the high pH taught by Kite, since such a pH is desirable in the composition of Kite. There is no reason to modify the compositions of Winnicki have a pH of 9.5-11.5, rather one of ordinary skill in the art could have adjusted the pH of the final composition, following the addition of any active ingredients taught by Winnicki, through known and routine methods to maintain the desirable pH taught by Kite.
Conclusion
No claims 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 SUSANNAH S ARMSTRONG whose telephone number is (571)272-0112. The examiner can normally be reached Mon-Fri 7:30-5 (Flex).
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, Sue X Liu can be reached at (571)272-5539. 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.
/SUSANNAH S ARMSTRONG/Examiner, Art Unit 1616
/SUE X LIU/Supervisory Patent Examiner, Art Unit 1616
Prosecution Insights