Prosecution Insights
Last updated: April 19, 2026
Application No. 17/922,886

METHYLTHIONINIUM COMPOUNDS FOR USE IN THE TREATMENT OF HYPOXEMIA

Non-Final OA §103§DP
Filed
Nov 02, 2022
Examiner
ELENISTE, PIERRE PAUL
Art Unit
1622
Tech Center
1600 — Biotechnology & Organic Chemistry
Assignee
Wista Laboratories Ltd.
OA Round
1 (Non-Final)
39%
Grant Probability
At Risk
1-2
OA Rounds
3y 6m
To Grant
71%
With Interview

Examiner Intelligence

Grants only 39% of cases
39%
Career Allow Rate
27 granted / 69 resolved
-20.9% vs TC avg
Strong +32% interview lift
Without
With
+31.6%
Interview Lift
resolved cases with interview
Typical timeline
3y 6m
Avg Prosecution
53 currently pending
Career history
122
Total Applications
across all art units

Statute-Specific Performance

§101
2.1%
-37.9% vs TC avg
§103
48.9%
+8.9% vs TC avg
§102
16.5%
-23.5% vs TC avg
§112
20.8%
-19.2% vs TC avg
Black line = Tech Center average estimate • Based on career data from 69 resolved cases

Office Action

§103 §DP
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 . Claim status Claims 1-30 are pending and have been examined on the merits. 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. 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 1-11, 13-15, 17 and 20-30 are rejected under 35 U.S.C. 103 as being unpatentable over Wischik et al. (WO 2020/020751) in view of Roma et al. Transplantation Proceedings, vol. 42, no. 2, Mar. 2010, pp. 601–04. Regarding claims 1 and 24-28, Wischik (abstract; page 1) teaches a therapeutic treatment of a neurodegenerative disorder with methylthioninium (MT)-containing compound. Wischik (page 14) teaches the following methylthioninium-containing compound: PNG media_image1.png 410 744 media_image1.png Greyscale Wischik (page 67, claim 1) teaches “administration provides a total daily dose of between 20.5 and 40, 20.5 and 60, 20.5 and 80 or 20.5 and 99 or 100 mg of MT to the subject per day, optionally split into 2 or more doses.” Wischik, however, does not explicitly teach a method of alleviating hypoxemia. However, Roma (page 601-602) teaches the use of methylene blue to improve hypoxemia in patient with Hepatopulmonary syndrome, leading to oxygen saturation between (85%–92%). While Roma does not explicitly use the phrase “alleviating”, however, the measurable benefits by methylene blue corresponds to alleviating hypoxemia by the increased of oxygen saturation. Given that methylene blue is a methylthioninium analogue, thus, it would have been obvious to a person of ordinary skill in the art (POSITA) to modify the teachings of Wischik in view of Roma to arrive at the claimed invention, because Roma discloses the use of a methylthioninium analogue to treat or improve hypoxemia. Regarding claims 2-9, Wischik (page 11), and as applied to claim 1 above, teaches oral administration of a total daily dose of methylthioninium analogues in the following range: PNG media_image2.png 208 714 media_image2.png Greyscale Regarding claims 10-15 and 17, Wischik does not explicitly teach blood oxygen saturation level (SpO2) or selecting the subject according to their SpO2 value. However, Roma (abstract; page 603, Table 1), and as applied to claim 1 above, teaches treatment for patient with Hepatopulmonary syndrome (HPS), a disease characterizes by low oxygen levels and hypoxemia. Roma (abstract; page 603, Table 1) teaches, before treatment, a patient with a SatO2 (%) of 71, which correlates with a SpO2 value below 95%; thus, both PNG media_image3.png 256 752 media_image3.png Greyscale values are within the same hypoxemic range. Roma (page 603, Table 1) also teaches treatment with methylene blue improves SatO2 (%) by 86 after 40 min. Therefore, it would have been obvious to a POSITA that patients with HPS have an SpO2 value below 95%, and arrive at the claimed invention, because treatment with methylene significantly improves SatO2 (%) by 86 after 40 min. Regarding claim 20, Wischik (page 72, claims 44 and 45), and as applied to claim 1 above, teaches the following: PNG media_image4.png 223 704 media_image4.png Greyscale Wischik (page 73, claim 50), teaches the following mono-protic acids for use with methylthioninium-containing compound: PNG media_image5.png 60 686 media_image5.png Greyscale Given this disclosure, it would have been obvious to a POSITA to select the appropriate protic acid from the provided selection, because Wishick provides motivation and expectation of success of using methylthioninium-containing compound with different mono-protic acids to arrive at the claimed invention. Regarding claim 21, Wischik (page 5), and as applied to claim 1 above, teaches the following compound, wherein p is 2 and HnX is HCl, reading on the instant claim. PNG media_image6.png 136 604 media_image6.png Greyscale Regarding claim 22, Wischik (page 74, claim 56), and as applied to claim 1 above, teaches the following compound, wherein H2A is 1,2-ethanedisulfonic acid, reading on the instant claim. PNG media_image7.png 172 302 media_image7.png Greyscale Regarding claim 23, Wischik (page 74, claim 56), and as applied to claim 1 above, teaches the following compound, wherein 2(HA) is p-toluenesulfonic acid, reading on the instant claim. PNG media_image8.png 154 392 media_image8.png Greyscale Regarding claim 29, Wischik (page 14, claim 56), and as applied to claim 1 above, teaches the following compound, reading on the instant claim. PNG media_image9.png 138 370 media_image9.png Greyscale Regarding claim 30, Wischik (page 15), and as applied to claim 1 above, teaches the following compound, reading on the instant claim. PNG media_image10.png 140 372 media_image10.png Greyscale Claim Objections It is noted that claims 12, 16 and 18-19 are free of the prior art. However, the claims are not allowed because they rely, directly or indirectly, on claim 1 that has been rejected. As a result, until this issue is remedied or resolved; the claims cannot be subject of allowance. Double Patenting The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969). A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b). The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13. The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer. Claims 1, 21 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4-6 and 9 of U.S. Patent No. US 10842796 in view of Roma et al. Transplantation Proceedings, vol. 42, no. 2, Mar. 2010, pp. 601–04. Although the claims at issue are not identical, they are not patentably distinct from each other because compounds claimed in US patent '796 are comparable to those of the instant claims. For example, claim 4 of the US patent ‘796 recites the LMTX compound of the following formula, that is identical to that of the instant claim 1 and 21. PNG media_image11.png 358 284 media_image11.png Greyscale Claims 5-6 and 9 of the US patent ‘796 also recites methylthioninium compound of the following formula, that is identical to that of the instant claim 22-24, 27 and 29. PNG media_image12.png 614 298 media_image12.png Greyscale The US patent ‘796 does teach hypoxemia. However, Roma (page 601-602) teaches the use of methylene blue to improve hypoxemia in patient with Hepatopulmonary syndrome, leading to oxygen saturation between (85%–92%). While Roma does not explicitly use the phrase “alleviating”, however, the measurable benefits by methylene blue corresponds to alleviating hypoxemia by the increased of oxygen saturation. Given that methylene blue is a methylthioninium analogue, thus, it would have been obvious to a person of ordinary skill in the art (POSITA) to modify the teachings of US patent ‘796 in view of Roma to arrive at the claimed invention, because Roma discloses the use of a methylthioninium analogue to treat or improve hypoxemia. Given that the claimed compounds of the instant claim are identical to that of the US patent ‘796 in view of Roma, without meaningful inventive distinction, thus the instant application is not in proper condition to warrant a Notice of Allowance. This is because, allowing both claims to issue as separate patents would unjustly extend the patent rights beyond the statutory term. Claims 1, 4-8, 20, 23-24 and 27-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-8, 11 and 18 of U.S. Patent No. US 11065256 in view of Roma et al. Transplantation Proceedings, vol. 42, no. 2, Mar. 2010, pp. 601–04. Although the claims at issue are not identical, they are not patentably distinct from each other because compounds claimed in US patent ‘256 are comparable to those of the instant claims. For example, claim 1 of the US patent ‘256 recites the LMTX compound of the following formula, that is identical to that of the instant claim 1. PNG media_image13.png 176 278 media_image13.png Greyscale Claim 3 of the US patent ‘256 teaches the following compound, as an example, that is identical to that of the instant claim 20. PNG media_image14.png 112 250 media_image14.png Greyscale Claims 4-7 of the US patent ‘256 teaches the following compound, as an example, that is identical to that of the instant claims 23-24 and 27-28. PNG media_image15.png 292 296 media_image15.png Greyscale Claims 8-9 and 18of the US patent ‘256 teaches the following compound, as an example, that is identical to that of the instant claims 4-7 and 29. PNG media_image16.png 206 296 media_image16.png Greyscale Claims 11 of the US patent ‘256 teaches the following compound, as an example, that is identical to that of the instant claim 30. PNG media_image17.png 300 288 media_image17.png Greyscale The US patent ‘256 does teach hypoxemia. However, Roma (page 601-602) teaches the use of methylene blue to improve hypoxemia in patient with Hepatopulmonary syndrome, leading to oxygen saturation between (85%–92%). While Roma does not explicitly use the phrase “alleviating”, however, the measurable benefits by methylene blue corresponds to alleviating hypoxemia by the increased of oxygen saturation. Given that methylene blue is a methylthioninium analogue, thus, it would have been obvious to a person of ordinary skill in the art (POSITA) to modify the teachings of US patent ‘256 in view of Roma to arrive at the claimed invention, because Roma discloses the use of a methylthioninium analogue to treat or improve hypoxemia. Given that the claimed compounds of the instant claim are identical to that of the US patent ‘256 in view of Roma, without meaningful inventive distinction, thus the instant application is not in proper condition to warrant a Notice of Allowance. This is because, allowing both claims to issue as separate patents would unjustly extend the patent rights beyond the statutory term. Claims 29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of U.S. Patent No. US 11759469 in view of Roma et al. Transplantation Proceedings, vol. 42, no. 2, Mar. 2010, pp. 601–04. Although the claims at issue are not identical, they are not patentably distinct from each other because compounds claimed in US patent ‘469 are comparable to those of the instant claims. For example, claims 1 and 5 of the US patent ‘469 recite a LMTM compound that is identical to that of the instant claim 29. PNG media_image18.png 112 272 media_image18.png Greyscale The US patent ‘469 does teach hypoxemia. However, Roma (page 601-602) teaches the use of methylene blue to improve hypoxemia in patient with Hepatopulmonary syndrome, leading to oxygen saturation between (85%–92%). While Roma does not explicitly use the phrase “alleviating”, however, the measurable benefits by methylene blue corresponds to alleviating hypoxemia by the increased of oxygen saturation. Given that methylene blue is a methylthioninium analogue, thus, it would have been obvious to a person of ordinary skill in the art (POSITA) to modify the teachings of US patent ‘469 in view of Roma to arrive at the claimed invention, because Roma discloses the use of a methylthioninium analogue to treat or improve hypoxemia. Given that the claimed compounds of the instant claim are identical to that of the US patent ‘469 in view of Roma, without meaningful inventive distinction, thus the instant application is not in proper condition to warrant a Notice of Allowance. This is because, allowing both claims to issue as separate patents would unjustly extend the patent rights beyond the statutory term. Claims 1, 4-8, 20, 23-24 and 27-30 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3-9 and 11 of U.S. Patent No. US 12128051 in view of Roma et al. Transplantation Proceedings, vol. 42, no. 2, Mar. 2010, pp. 601–04. Although the claims at issue are not identical, they are not patentably distinct from each other because compounds claimed in US patent ‘051 are comparable to those of the instant claims. For example, claim 1 of the US patent ‘051 recites the methylthioninium compound of the following formula, that is identical to that of the instant claim 1. PNG media_image19.png 166 284 media_image19.png Greyscale Claim 3 of the US patent ‘051 teaches the following compound, as an example, that is identical to that of the instant claims 20. PNG media_image20.png 122 254 media_image20.png Greyscale Claims 4-7 of the US patent ‘051 teaches the following compound, as an example, that is identical to that of the instant claims 23-24 and 27-28. PNG media_image21.png 328 292 media_image21.png Greyscale Claims 8-9 of the US patent ‘051 teaches the LMTM compound, as an example, that is identical to that of the instant claims 4-8 and 29. PNG media_image22.png 224 292 media_image22.png Greyscale Claims 11 of the US patent ‘051 teaches the following compound, as an example, that is identical to that of the instant claim 30. PNG media_image23.png 274 288 media_image23.png Greyscale The US patent ‘051 does teach hypoxemia. However, Roma (page 601-602) teaches the use of methylene blue to improve hypoxemia in patient with Hepatopulmonary syndrome, leading to oxygen saturation between (85%–92%). While Roma does not explicitly use the phrase “alleviating”, however, the measurable benefits by methylene blue corresponds to alleviating hypoxemia by the increased of oxygen saturation. Given that methylene blue is a methylthioninium analogue, thus, it would have been obvious to a person of ordinary skill in the art (POSITA) to modify the teachings of US patent ‘051 in view of Roma to arrive at the claimed invention, because Roma discloses the use of a methylthioninium analogue to treat or improve hypoxemia. Given that the claimed compounds of the instant claim are identical to that of the US patent ‘051 in view of Roma, without meaningful inventive distinction, thus the instant application is not in proper condition to warrant a Notice of Allowance. This is because, allowing both claims to issue as separate patents would unjustly extend the patent rights beyond the statutory term. Claims 26-28 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. US 12263175 in view of Roma et al. Transplantation Proceedings, vol. 42, no. 2, Mar. 2010, pp. 601–04. Although the claims at issue are not identical, they are not patentably distinct from each other because compounds claimed in US patent ‘175 are comparable to those of the instant claims. For example, claims 1-5 of the US patent ‘175 recite a LMTM compound that is identical to that of the instant claim 26. Claims 2-5 of the US patent ‘175 teaches the total daily dose is PNG media_image18.png 112 272 media_image18.png Greyscale between 20.5 and 40 mg that falls within the range of the instant claim 27-28. The US patent ‘175 does teach hypoxemia. However, Roma (page 601-602) teaches the use of methylene blue to improve hypoxemia in patient with Hepatopulmonary syndrome, leading to oxygen saturation between (85%–92%). While Roma does not explicitly use the phrase “alleviating”, however, the measurable benefits by methylene blue corresponds to alleviating hypoxemia by the increased of oxygen saturation. Given that methylene blue is a methylthioninium analogue, thus, it would have been obvious to a person of ordinary skill in the art (POSITA) to modify the teachings of US patent ‘175 in view of Roma to arrive at the claimed invention, because Roma discloses the use of a methylthioninium analogue to treat or improve hypoxemia. Given that the claimed compounds of the instant claim are identical to that of the US patent ‘175 in view of Roma, without meaningful inventive distinction, thus the instant application is not in proper condition to warrant a Notice of Allowance. This is because, allowing both claims to issue as separate patents would unjustly extend the patent rights beyond the statutory term. Claims 29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 of U.S. Patent No. US 12280061 in view of Roma et al. Transplantation Proceedings, vol. 42, no. 2, Mar. 2010, pp. 601–04. Although the claims at issue are not identical, they are not patentably distinct from each other because compounds claimed in US patent ‘175 are comparable to those of the instant claims. For example, claims 1 of the US patent ‘175 recites a LMTM compound that is identical to that of the instant claim 29. PNG media_image18.png 112 272 media_image18.png Greyscale The US patent ‘061 does teach hypoxemia. However, Roma (page 601-602) teaches the use of methylene blue to improve hypoxemia in patient with Hepatopulmonary syndrome, leading to oxygen saturation between (85%–92%). While Roma does not explicitly use the phrase “alleviating”, however, the measurable benefits by methylene blue corresponds to alleviating hypoxemia by the increased of oxygen saturation. Given that methylene blue is a methylthioninium analogue, thus, it would have been obvious to a person of ordinary skill in the art (POSITA) to modify the teachings of US patent ‘061 in view of Roma to arrive at the claimed invention, because Roma discloses the use of a methylthioninium analogue to treat or improve hypoxemia. Given that the claimed compounds of the instant claim are identical to that of the US patent ‘061 in view of Roma, without meaningful inventive distinction, thus the instant application is not in proper condition to warrant a Notice of Allowance. This is because, allowing both claims to issue as separate patents would unjustly extend the patent rights beyond the statutory term. Provisional nonstatutory double patenting Claim 1, 17-20, 26 and 29 provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claim 1, 20-23 and 29-30 of copending Application No. 17/922,837. Although the claims at issue are not identical, they are not patentably distinct from each other because Claim 1 of co-pending application is drawn to a methylthioninium compound of the following formula, that is identical to that of the instant claim 1. PNG media_image24.png 246 664 media_image24.png Greyscale Claim 17 of co-pending application is drawn to the following formula, that is identical to that of the instant claim 20. PNG media_image25.png 154 292 media_image25.png Greyscale Claim 18 of co-pending application is drawn to the following formula, that is identical to that of the instant claim 21. PNG media_image26.png 138 300 media_image26.png Greyscale Claim 19 of co-pending application is drawn to the following formula, that is identical to that of the instant claim 22. PNG media_image27.png 152 294 media_image27.png Greyscale Claim 20 of co-pending application is drawn to the following formula, that is identical to that of the instant claim 23. PNG media_image28.png 132 300 media_image28.png Greyscale Claim 26 of co-pending application is drawn to the following compound, that is identical to that of the instant claim 29. PNG media_image29.png 148 328 media_image29.png Greyscale Claim 29 of co-pending application is drawn to the following compound, that is identical to that of the instant claim 30. PNG media_image30.png 354 368 media_image30.png Greyscale This suggests the overlap conflicting claims are not patentably distinct between the instant and co-pending application. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented. Conclusion Therefore, no claims are allowed. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PIERRE PAUL ELENISTE whose telephone number is (571)270-0589. The examiner can normally be reached Monday - Friday 8:00 am - 5:00 pm (EST). 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, JAMES H ALSTRUM-ACEVEDO can be reached at (571) 272-5548. 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. /P.P.E./Examiner, Art Unit 1622 /JAMES H ALSTRUM-ACEVEDO/Supervisory Patent Examiner, Art Unit 1622
Read full office action

Prosecution Timeline

Nov 02, 2022
Application Filed
Apr 07, 2023
Response after Non-Final Action
Sep 18, 2025
Non-Final Rejection — §103, §DP (current)

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Prosecution Projections

1-2
Expected OA Rounds
39%
Grant Probability
71%
With Interview (+31.6%)
3y 6m
Median Time to Grant
Low
PTA Risk
Based on 69 resolved cases by this examiner. Grant probability derived from career allow rate.

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