Ex Parte Yamamoto et alDownload PDFPatent Trial and Appeal BoardJul 15, 201612751195 (P.T.A.B. Jul. 15, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 121751,195 03/31/2010 65565 7590 07119/2016 SUGHRUE-265550 2100 PENNSYLVANIA AVE. NW WASHINGTON, DC 20037-3213 FIRST NAMED INVENTOR Yuji Yamamoto 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 ATTORNEY DOCKET NO. CONFIRMATION NO. Ql 18336 1207 EXAMINER KEYS,ROSALYNDANN ART UNIT PAPER NUMBER 1671 NOTIFICATION DATE DELIVERY MODE 07/19/2016 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): SUGHRUE265550@SUGHRUE.COM PPROCESSING@SUGHRUE.COM USPTO@sughrue.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte YUJI YAMAMOTO and HIROKI YOSHIOKA Appeal2014-004735 Application 12/751,195 Technology Center 1600 Before DEMETRA J. MILLS, FRANCISCO C. PRATS, and JACQUELINE T. HARLOW, Administrative Patent Judges. MILLS, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134. The Examiner has rejected the claims for obviousness. We have jurisdiction under 35 U.S.C. § 6(b). STATEMENT OF CASE The present invention relates to a purification method of a high-molecular-weight polyethylene glycol compound. More specifically, the invention relates to a purification method of obtaining a high-molecular-weight activated polyethylene glycol compound to be used in pharmaceutical uses mainly including chemical modification of physiologically active proteins such as enzymes and the other drugs and chemical modification of liposomes, polymer micelles, and the like in drug delivery systems Appeal2009-005511 Application 10/739,849 or a highly pure high-molecular-weight polyethylene glycol raw material useful as a starting material of the compound. Spec. 1. The following claim is representative. 1. A purification method of a high-molecular-weight polyethylene glycol compound through removing, from a high-molecular-weight polyethylene glycol compound whose total average number of moles of ethylene oxide units added in the molecule is 220 to 4500, a polyethylene glycol impurity different in molecular weight, which comprises: (A) a mixing step of, in a state that the high-molecular-weight polyethylene glycol compound is dissolved in at least one of water and one or more organic solvents selected from the group consisting of aromatic hydrocarbon solvents having 8 or less carbon atoms in total and ester compound solvents having 5 or less carbon atoms in total, mixing the water and the one or more organic solvents; and (B) a separation step of separating the resulting mixture into an organic layer and an aqueous layer and separating the organic layer from the aqueous layer. Cited References Gurgiolo Boehmke Wolfe et al. Reeve et al. us 3,492,358 us 4,322,312 us 4,962,238 us 5,800,711 Grounds of Rejection Jan.27, 1970 Mar. 30, 1982 Oct. 9, 1990 (Wolfe) Sept. 1, 1998 (Reeve) Claims 1-23 stand rejected under 35 U.S.C. § 103(a) as being unpatentable over Boehmke, in view of Wolfe, Gurgiolo, and Reeve. 2 Appeal2014-004735 Application 12/751,195 FINDINGS OF FACT The Examiner's findings of fact are set forth in the Answer at pages 3-10. PRINCIPLES OF LAW In making our determination, we apply the preponderance of the evidence standard. See, e.g., Ethicon, Inc. v. Quigg, 849 F.2d 1422, 1427 (Fed. Cir. 1988) (explaining the general evidentiary standard for proceedings before the Office). "The combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results." KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007). Under§ 103, "there must be some articulated reasoning with some rational underpinning to support the legal conclusion of obviousness." KSR Int'! Co. v. Teleflex, Inc., 550 U.S. 398, 418 (2007) (citation omitted). "If a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond his or her skill." Id. at 416. Obviousness is determined on the basis of the evidence as a whole and the relative persuasiveness of the arguments. See In re Oetiker, 977 F.2d 1443, 1445 (Fed.Cir.1992). Obviousness The Examiner finds that Boehmke teaches a process for the purification of non- ionic emulsifiers which are of the type comprising addition products of alkylene oxides and compounds containing 3 Appeal2014-004735 Application 12/751,195 hydroxyl groups, carboxyl groups or carboxamide groups from impurities comprising polyglycols, polyols or polyol- polyglycols originating from their preparation (see entire disclosure). The non-ionic emulsifiers to be purified have a chain of over 20 alkylene oxide units (see claim 7). Such compounds are suggestive of the claimed high-molecular weight polyethylene glycol compound. The process is characterized in that an amount of water approximately corresponding to that of the impurities is added to solutions of the reaction mixtures in water-immiscible organic solvents, the organic layer and aqueous layer separate and the aqueous layer is separated off (see for example the paragraph bridging columns 2 and 3 and claim 1 ). Ans. 3. The Examiner finds that Boehmke teaches that the preferred water-immiscible organic solvents are aromatic solvents such as benzene, toluene, and xylene (see col. 2, lines 27-35). The purification can be achieved at low or only slightly elevated temperatures (see col. 2, lines 51-60). In an advantageous embodiment of the emulsifier purification consists in stirring in the 40-70% strength organic solvent with 2-25% water at 20-50°C (see the paragraph bridging col. 2 and 3 and claim 5). Ans. 3. Boehmke teaches the use of the claimed additive solvents, toluene and benzene. See Ans. 3; Spec. 12 and Boehmke, col. 2, 11. 27-39. The Examiner finds that Boehmke does not teach the use of an organic or inorganic salt dissolved in the water, or carrying out the mixing and separation at temperatures higher than 50°C. Ans. 3. The Examiner relies on Wolfe, Gurgiolo, and Reeve to make up for these deficiencies. Ans. 3. The Examiner concludes that 4 Appeal2014-004735 Application 12/751,195 One having ordinary skill in the art at the time the invention was made would have found it obvious that the purification process of Boehmke could be modified to include the use of the claimed additive solvents, the use of an organic or inorganic salt dissolved in the water, or carrying out the mixing and separation at temperatures higher than 50°C, since Wolfe et al., Gurgiolo, and Reeve et al. teach that such solvents and salts have been shown to be useful for extraction purification of polyoxyalkylene glycol compounds and Wolfe et al. and Reeve et al. have shown that temperatures higher than 50°C are also suitable temperatures for carrying out purification of polyoxyalkylene glycol compounds. Therefore, all the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art at the time of the invention. Ans. 4--5. Appellants contend that, Boehn:1ke teaches that his process provides the ability to purify adducts with 20-100 mo ls of ethylene oxide units (see column 2, lines 51-54), which is outside the scope of the claimed high- molecular weight polyethylene glycol compound whose total average number of moles of ethylene oxide units added in the molecule is 220 to 4500. App. Br. 6. Appellants further argue that Boehmke specifically teaches that previously known methods are not adequate for purifying emulsifiers with a chain of over 20 alkylene oxide units since they display no turbidity point on heating. Column 2, lines 23-26. Then Boehmke clearly states "the purification process according to the invention extends the known processes by providing them with the ability to also purify adducts with 20-100 mo ls of ethylene oxide units ... " Column 2, lines 51-54. 5 Appeal2014-004735 Application 12/751,195 App. Br. 7. Appellants argue that, "under the conditions taught by Boehmke, high-molecular-weight polyethylene glycols are all distributed in an aqueous layer so that removal of polyethylene glycols as an impurity having a molecular weight different from that of the high-molecular-weight polyethylene glycols which is an object of the present invention, cannot be achieved." App. Br. 9. ANALYSIS We agree with the Examiner's fact finding, statement of the rejection and responses to Appellants' arguments as set forth in the Answer. We find that the Examiner has provided evidence adequate to support a prima facie case of obviousness. We provide the following additional comment to the Examiner's argument set forth in the Final Rejection and Answer. Appellants do not provide separate arguments for dependent claims, therefore we select claim 1 as representative claim. \Vith respect to 1A .. ppellants' argument that Boehmke teaches a process outside the scope of the claimed high-molecular weight polyethylene glycol compound whose total average number of moles of ethylene oxide units added in the molecule is 220 to 4500, the Examiner responds, arguing that, "Boehmke teaches in claim 7 that his process provides the ability to purify adducts with over 20 alkylene oxide units. This is within the scope of the claimed high-molecular weight polyethylene glycol compound whose total average number of moles of ethylene oxide units added in the molecule is 220 to 4500, since 220 to 4500 is over 20." Ans. 5-6. The Examiner further argues that "Boehmke discloses the use of low or slightly elevated temperatures (see col. 2, lines 51-60) and expressly discloses the 6 Appeal2014-004735 Application 12/751,195 temperature range of 20-50QC, which overlaps the claimed temperature range at 50QC. Appellants have not rebutted the Examiner's argument or evidence with a sufficient showing. "If a technique has been used to improve one process, and a person of ordinary skill in the art would recognize that it would improve similar processes in the same way, using the technique is obvious unless its actual application is beyond his or her skill." KSR, 550 U.S. at 416. In the present case, the prior art processes show an improvement in removal of polyethylene glycol impurities from polyethylene glycol-containing emulsifiers with chains over 20 alkylene oxide units, using aromatic hydrocarbon solvents having 8 or less carbon atoms, in the presence of water, as required by claim 1. See, e.g., Boehmke, col. 2, 11. 27-39. This technique is known to be useful, as disclosed in Reeve, for poloxamers ranging up to 16,000 daltons. Col. 4, 11. 53-64. Thus, one of ordinary skill in the art \'l/ould have found it obvious ( \'l1ith a reasonable expectation of success) to use this known purification technique for removing lower molecular weight byproducts from polyethylene glycol- containing emulsifiers compounds encompassed by claim 1, including those having a molecular weight of about 20,000, as the technique was shown to be successful for poloxamers ranging up to 16,000 daltons in Reeve. Appellants argue that "neither of Wolfe nor Gurgiolo teach the removal from a high-molecular weight polyethylene glycol compound whose total average number of moles of ethylene oxide units added in the molecule is 220 to 4500, a polyethylene glycol impurity different in molecular weight." App. Br. 10. For the reasons given above, we are not persuaded that Wolfe fails to suggest the impurity removal step of claim 1. 7 Appeal2014-004735 Application 12/751,195 We agree with the Examiner, moreover, that Gurgiolo, and Reeve teach that the solvents and salts taught in those references have been shown to be useful for extraction purification of polyoxyalkylene glycol compounds, and Wolfe and Reeve have shown that temperatures higher than 50QC are also suitable temperatures for carrying out purification of polyoxyalkylene glycol compounds. See Ans. 4--5 (citing Gurgiolo, cols. 2-3; Reeve, cols. 5---6). Finally, we agree with the Examiner with respect to Appellants' arguments regarding Boehmke' s disclosure about the prior art removal of impurities. As the Examiner argued, the prior art methods mentioned in the background section of Boehmke do not include the use of an organic solvent in combination with water, as taught by Boehmke. Further, the disclosure of Boehmke being applicable to purifying adducts with 20-100 mols of ethylene oxide units, as disclosed in col. 2, lines 51-55, should not be limiting, since Boehmke disclose that the teaching is applicable to emulsifiers having 20 or more alkylene oxide units (see claim 7). Ans. 7. Nor are we persuaded by Appellants' Declaration under 37 C.F.R. § 1.132. Br. 11. The Declaration states that the effective purification of high- molecular-weight polyethylene glycol compounds cannot be achieved with the system of Reeve et al using n-propanol as a solvent. Dec. 2; Br. 11. We are not persuaded. Rather than n-propanol, as solvents, representative claim 1 recites the use of either aromatic hydrocarbon solvents having 8 or less carbon atoms in total or ester compound solvents having 5 or less carbon atoms in total. App. Br. 13. Reeve discloses that it is known to remove lower molecular weight fractions from polymeric glycols by dissolving the 8 Appeal2014-004735 Application 12/751,195 polymeric glycol in cyclohexane and/or toluene. Col. 2, 11. 45. Furthermore, the Examiner also relies on Wolfe and Gurgiolo for the use of the claimed solvents. Appellants are comparing and arguing the references individually instead of in combination. With respect to Appellants argument concerning the distribution of high-molecular-weight polyethylene glycols in an aqueous layer in Boehmke, we note that pending claim 20 also indicates that the high- molecular-weight polyethylene glycol compound is collected from the aqueous layer. Appellants have not shown how the disclosure of Boehmke is distinguished from the method claimed. Furthermore, claim 1 step B) does not appear to indicate whether the polyethylene glycols are present in the organic layer or the aqueous layer. The remaining arguments of Appellants have been addressed fully in the Answer, and we adopt them as our own. We affirm the obviousness rejection for the reasons of record. CONCLUSION OF LAW The cited references support the Examiner's obviousness rejection, which is affirmed for the reasons of record. All pending, rejected claims fall. TIME PERIOD FOR RESPONSE No time period for taking any subsequent action in connection with this appeal may be extended under 37 C.F.R. § 1.136(a). AFFIRMED 9 Copy with citationCopy as parenthetical citation