Medtrade Products Limited

Patent Trials and Appeals Board

Mar 25, 2022

2021003121 (P.T.A.B. Mar. 25, 2022)

UNITED STATES PATENT AND TRADEMARK OFFICE UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O. Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 14/387,331 09/23/2014 June Gladman WIL-023834 US PCT 6689 26294 7590 03/25/2022 TAROLLI, SUNDHEIM, COVELL & TUMMINO L.L.P. 1300 EAST NINTH STREET, SUITE 1700 CLEVELAND, OH 44114 EXAMINER KRISHNAN, GANAPATHY ART UNIT PAPER NUMBER 1623 NOTIFICATION DATE DELIVERY MODE 03/25/2022 ELECTRONIC Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. Notice of the Office communication was sent electronically on above-indicated "Notification Date" to the following e-mail address(es): docketing@tarolli.com rkline@tarolli.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte JUNE GLADMAN, CRAIG HARDY, and ANDREW HOGGARTH1 Appeal 2021-003121 Application 14/387,331 Technology Center 1600 Before ERIC B. GRIMES, JEFFREY N. FREDMAN, and JOHN G. NEW, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims to a method of making a low endotoxin chitosan, which have been rejected based on obviousness and obviousness-type double patenting. We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE. 1 Appellant identifies the real party in interest as Medtrade Products Limited. Appeal Br. 3. “Appellant” refers to “applicant” as defined in 37 C.F.R. § 1.42. Appeal 2021-003121 Application 14/387,331 2 STATEMENT OF THE CASE “Chitosan is particularly useful in the preparation of haemostatic materials for use in controlling bleeding.” Spec. 1:6-7. “In order to utilise chitosan in the preparation of haemostatic materials . . . , it is necessary to ensure that the chitosan has a sufficiently low concentration of endotoxin.” Id. at 1:18-20. The Specification describes “an effective way of obtaining an alkali chitosan having a low endotoxin concentration.” Id. at 4:15-16. “Since the molecular weight of endotoxins can vary significantly, endotoxin concentration is measured in endotoxin units (EU) per gram of material.” Id. at 4:23-24. Claims 1, 2, 8, 11, 12, 15, 20, 21, 23, 28, 29, 31, 33, and 43-54 are on appeal. Claim 1 is the only independent claim and is reproduced below: 1. A process for producing a low endotoxin alkali chitosan, having an endotoxin concentration of less than 50 EU/g, the process comprising the steps of: (a) contacting chitosan with an alkali solution having a concentration of from 0.01M to 0.2M to form a mixture; and (b) leaving the mixture for at least 12 hours. Appeal Br. 24 (Claims App.). Appeal 2021-003121 Application 14/387,331 3 The claims stand rejected as follows: Claims 1, 2, 8, 11, 12, 15, 20, 21, 23, 28, 29, 31, 33, and 43-54 under 35 U.S.C. § 103(a) as obvious based on Hung,2 Gislason,3 Partain,4 and Baker5 (Final Action6 3); and Claims 1, 2, 8, 11, 12, 15, 20, 21, 23, 28, 29, 31, 33, and 43-54, provisionally, for obviousness-type double patenting based on any of claims 27-30 of application 14/894,478,7 claims 25-27 of application 14/894,475,8 or claims 1-3, 6, 9, 10, 13, 17, 18, 20, 25, 26, 28, 30 and 39-42 of application 14/894,473, each in view of Hung, Gislason, Partain, and Baker (Final Action 11). OPINION Obviousness Claims 1, 2, 8, 11, 12, 15, 20, 21, 23, 28, 29, 31, 33, and 43-54 stand rejected as obvious based on Hung, Gislason, Partain, and Baker. The Examiner finds that Hung “teaches preparation of low endotoxin chitosan” by contacting the chitosan with an “alkali solution [that] can have a concentration ranging from 0.25M to about 1M and the time of contact with the alkali can be greater than 6 hours if so desired.” Final Action 3. 2 WO 2005/034865 A2 (pub. Apr. 21, 2005). 3 WO 2006/134614 A1 (pub. Dec. 21, 2006). 4 US 4,946,870 (iss. Aug. 7, 1990). 5 WO 2008/063503 A2 (pub. May 29, 2008). 6 Office Action mailed January 30, 2020. 7 The ’478 Application has issued as U.S. Patent No. 9,867,900 B2. 8 The ’475 Application has issued as U.S. Patent No. 10,933,160 B2. Appeal 2021-003121 Application 14/387,331 4 The Examiner finds that “[t]he lower end of the concentration range, namely 0.25M, taught by Hung et al is closer to the higher end of the concentration range recited in claim 1, namely 0.2M.” Id. at 3-4. The Examiner also finds that Hung’s results would show a skilled artisan “that a longer contact time of the chitosan with alkali solution reduces the endotoxin level further.” Id. at 4. The Examiner concludes that, “[t]herefore, there is suggestion to use lower concentration of the alkali and extend the time of contact with the alkali in order to obtain a low endotoxin chitosan as in instant claim 1.” Id. The Examiner finds that Gislason teaches “a low endotoxin alkali chitosan having an endotoxin level of <30 EU/g. It is obtained by contacting chitosan with alkali. . . . The contact with alkali is for 43 hours (step b in claim 1).” Id. The Examiner concludes “[t]he artisan would adjust the time of contact and adjust the alkali concentration in view of the teachings of Hung and Gislason. Using the lowest possible concentration of the alkali also reduces the cost of the process.” Id. at 5. In addition, as relevant to claim 1, the Examiner finds that Baker teaches that “chitosan is used in medical and biological applications involving open wound, blood and organs and for this purpose chitosan having low level of endotoxin is required. . . . This provides motivation to reduce the endotoxin level as low as possible.” Id. at 5-6.9 9 The Examiner relies on Partain only with respect to certain dependent claims. Final Act. 5. We find it unnecessary to discuss Partain with respect to independent claim 1. Appeal 2021-003121 Application 14/387,331 5 The Examiner concludes that it would have been obvious to make low endotoxin chitosan via contact of chitosan with an alkali solution having a concentration of from 0.01M to 0.2M for at least about 12 hours (as in claim 1) since an analogous method involving contacting chitosan with a base having a concentration close to the instant range . . . for making low endotoxin chitosan are known in the art. Id. at 6. Appellant argues that the Examiner erred in “conclud[ing] that the skilled artisan would have arrived at the recited NaOH range because Appellants have provided evidence of criticality of the claimed NaOH concentration.” Appeal Br. 14. Specifically, Appellant argues, “the test data demonstrates a significant decrease in the haemostatic ability of a chitosan salt haemostat when increasing NaOH concentration from 0.2M to 0.25M in the preparation of the recited low endotoxin alkali chitosan.” Id. at 15. Appellant also argues that “the chitosan salt haemostats produced after contact with an alkali concentration according to the claimed invention showed significant improvement (i.e., shorter time to blood immobilisation).” Id. Appellant argues, therefore, that “[t]he data in the Table in paragraph 5.3 and the images in paragraph 5.2 of Appellant[’]s test data demonstrate the significance of the upper limit of the claimed range.” Id. at 16. We agree with Appellant that the Examiner has not persuasively shown that the claimed process would have been obvious to a person of ordinary skill in the art based on the cited references. Hung discloses “methods for making and using . . . water-soluble chitosan having a low concentration of endotoxin.” Hung 1:16-17. “[T]he method for making Appeal 2021-003121 Application 14/387,331 6 water-soluble chitosan comprises contacting water-insoluble chitosan with a NaOH solution for a first period of time of greater than about one hour,” followed by further processing. Id. at 2:11-13. “Desirably, the basic solution used to contact the water-insoluble chitosan comprises a NaOH solution having a molar concentration ranging from 0.25M NaOH to about 1.0M NaOH, more desirably a 1.0M NaOH solution.” Id. at 6:23-26. “Desirably, the period of time is greater than or equal to about 2 hours, . . . ; however, the period of time may even be greater than 6 hours if so desired.” Id. at 6:16-18. Gislason “provide[s] methods and compositions of highly purified partially deacetylated chitin for therapeutic applications.” Gislason 2:40-41. Gislason’s Example 1 states: “Chitin powder [] was added [] to 50% NaOH. . . . Subsequently, fine crushed 3-10 mm ice . . . was added to the alkali slurry to dissolve the chitin. After 2 h . . . , temperature . . . was increased and deacetylation reaction carried out at 16°C for 40 h. After deacetylation[,] . . . endotoxins are dramatically reduced (<30 EU/g).” Id. at 11:9-14. Appellant calculates that Gislason’s alkali concentration is “well above Appellants’ claimed range of 0.01M - 0.20M.” Appeal Br. 19. The Examiner does not dispute this assertion. See Ans. 8-10. As noted above, the Examiner cites Partain only with respect to limitations of dependent claims, and cites Baker only as providing “motivation to reduce the endotoxin level as low as possible.” Ans. 5-6. Thus, the closest alkali concentration to the 0.01M to 0.2M range of claim 1 is the lower endpoint of Hung’s 0.25-1.0M NaOH. Appeal 2021-003121 Application 14/387,331 7 The Examiner reasons that using the lower concentration claimed would nonetheless have been obvious because the prior art taught “an analogous method involving contacting chitosan with a base having a concentration close to the instant range.” Final Action 6. In line with this reasoning, the Federal Circuit has stated that “a prima facie case of obviousness exists when the claimed range and the prior art range do not overlap but are close enough such that one skilled in the art would have expected them to have the same properties.” In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003). Here, however, the evidence of record shows that chitosan treated with 0.2M NaOH does not have the same properties as chitosan treated with 0.25M NaOH. Appellant’s Evidence Appendix includes a “[c]opy of test data submitted with Appellants’ Amendment dated December 2, 2019.” Appeal Br. 31. The test data, entitled “Assessment into the effect of the molarity of NaOH on Chitosan,” was signed by inventor Andrew Hoggarth on February 13, 2019, “indicat[ing] approval of this report.” Test Data 1. The Examiner has not disputed the accuracy of Appellant’s data. See Ans. 9-10. The test data “evaluate[d] the effect of washing the chitosan in different molarities of sodium hydroxide for a period of 12hrs on the final performance of the product when converted to the chitosan salt haemostat.” Id. at 2. The data show that, after 12 hours in 1% acetic acid, the loss of viscosity was 12.00% for heparin treated with 0.2M NaOH but was 29.33% for heparin treated with 0.25M NaOH. Id. at 3, §§ 4.1, 5.1. Appeal 2021-003121 Application 14/387,331 8 In addition, after blood was added to test samples, visual observation of the chitosan treated with 0.2M NaOH showed “[a]ll blood was absorbed into the granules. No free blood visible.” Id. at 3, §§ 4.2, 5.2. After the plate was tilted to allow draining, free blood measured 0.05g. Id. Chitosan treated with 0.25M NaOH showed “[v]isible free blood not absorbed into test article,” and free blood after draining totaled 0.42g. Id. Finally, the time required for immobilization after adding blood to test samples was 2.13 minutes for chitosan treated with 0.2M NaOH (a 70.4% increase above the control) and 3.33 minutes for chitosan treated with 0.25M NaOH (a 166.4% increase above the control). Id. at 4, § 5.3. The report concludes that [t]he data indicates that there is minimal effect on the chitosan when washed with sodium hydroxide with a molarity lower than 0.2M. At 0.25M and above the impact on the chitosan in terms of chain length is significant. This is shown by the higher percentage change in viscosity whereby the viscosity is reduced. When converted into the final proposed haemostatic product, viscosity is a key parameter in that the gel viscosity helps aid the gel plug when creating haemostasis. Id. at 5, § 6. The report also states that [t]he other factor is blood absorbency, immobilization. The preferred use is to apply the final product and create haemostasis in conjunction with 3 minutes compression. If the final device requires over 3 minutes to absorb and fully immobilize the blood, then the bleed with continue. The data shows that the absorbency potential of the final product and time to blood immobilization is beyond the target for chitosan washed with 0.25M NaOH and above. Id. Appeal 2021-003121 Application 14/387,331 9 The test data therefore provide evidence that the 0.2M upper limit of the NaOH concentration recited in the claims is critical to using the resulting product as a hemostatic agent: the properties of chitosan treated with 0.2M NaOH make it more suitable for use in hemostasis than chitosan treated with 0.25M NaOH. The Examiner responds that [t]he results shown in Table 3 in paragraph 5.3 and the images in paragraph 5.2 of Appellant’s test data show the effect of the alkali concentration and the extent of degradation of chitosan from which an alkali concentration range that is effective for reducing the endotoxin level without extensive degradation of chitosan has been determined. This is suggested by the teachings of Hung and Baker as set forth above. Ans. 9-10. The Examiner, however, has not pointed to any specific teachings in Hung or Baker that would have led a skilled artisan to use 0.2M NaOH in Hung’s process in order to avoid the degradation of chitosan that is evidenced in Appellant’s test data. To the contrary, Hung suggests using a minimum of 0.25M NaOH in its process (Hung 6:23-26), which is shown by Appellant’s data to result in chitosan that is less useful as a hemostat. In summary, we conclude that the Examiner has not persuasively shown that the process of claim 1 would have been obvious based on the cited references. We reverse the rejection of claims 1, 2, 8, 11, 12, 15, 20, 21, 23, 28, 29, 31, 33, and 43-54 under 35 U.S.C. § 103(a) based on Hung, Gislason, Partain, and Baker. Appeal 2021-003121 Application 14/387,331 10 Obviousness-type Double Patenting Claims 1, 2, 8, 11, 12, 15, 20, 21, 23, 28, 29, 31, 33, and 43-54 stand provisionally rejected for obviousness-type double patenting based on the claims of the ’478 application, the ’475 application, or the ’473 application, in view of Hung, Gislason, Partain, and Baker. The Examiner finds that the “claims of ’478, 475 and ’473 are also drawn to process/method for making chitosan,” but “differ from the instant claims in that . . . the copending claims also include chitin.” Final Action 12. The Examiner concludes that “[i]t would have been obvious . . . that the instant chitosan and its salts could be made using the instant process in view of the secondary references, the teachings of which are set forth above.” Id. Thus, the obviousness-type double patenting rejections depend on the same findings and reasoning as the obviousness rejection discussed above, and we reverse them for the same reason. Appeal 2021-003121 Application 14/387,331 11 DECISION SUMMARY In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 2, 8, 11, 12, 15, 20, 21, 23, 28, 29, 31, 33, 43-54 103(a) Hung, Gislason, Partain, Baker 1, 2, 8, 11, 12, 15, 20, 21, 23, 28, 29, 31, 33, 43-54 1, 2, 8, 11, 12, 15, 20, 21, 23, 28, 29, 31, 33, 43-54 Provisional Nonstatutory Double Patenting 14/894,478, Hung, Gislason, Partain, Baker 1, 2, 8, 11, 12, 15, 20, 21, 23, 28, 29, 31, 33, 43-54 1, 2, 8, 11, 12, 15, 20, 21, 23, 28, 29, 31, 33, 43-54 Provisional Nonstatutory Double Patenting 14/894,475, Hung, Gislason, Partain, Baker 1, 2, 8, 11, 12, 15, 20, 21, 23, 28, 29, 31, 33, 43-54 1, 2, 8, 11, 12, 15, 20, 21, 23, 28, 29, 31, 33, 43-54 Provisional Nonstatutory Double Patenting 14/894,473, Hung, Gislason, Partain, Baker 1, 2, 8, 11, 12, 15, 20, 21, 23, 28, 29, 31, 33, 43-54 Overall Outcome 1, 2, 8, 11, 12, 15, 20, 21, 23, 28, 29, 31, 33, 43-54 REVERSED