ECOSYNTHETIX LTD.Download PDFPatent Trials and Appeals BoardAug 25, 20212021000539 (P.T.A.B. Aug. 25, 2021) Copy Citation 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. 14/360,503 05/23/2014 Steven Bloembergen PAT 92237W-2 1386 42534 7590 08/25/2021 BORDEN LADNER GERVAIS LLP 1300-100 QUEEN ST OTTAWA, ONTARIO K1P 1J9 CANADA EXAMINER BROWE, DAVID ART UNIT PAPER NUMBER 1617 NOTIFICATION DATE DELIVERY MODE 08/25/2021 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): ipinfo@blg.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte STEVEN BLOEMBERGEN, IAN J. MCLENNAN, NATHAN JONES, AREET KRSNA GANESH SHERMON, ABDEL ELSAYED, and JUEWEN LIU ____________ Appeal 2021-000539 Application 14/360,503 Technology Center 1600 ____________ Before DONALD E. ADAMS, ULRIKE W. JENKS, and TIMOTHY G. MAJORS, Administrative Patent Judges. ADAMS, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from Examiner’s decision to reject claims 1, 3, 6–9, and 34–37 (Appeal Br. 1; see also Reply Br.2 2). We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party in interest as “GreenMark Biomedical Inc.” (Appellant’s September 13, 2019, Appeal Brief (Appeal Br.) 3). 2 Appellant’s February 20, 2020, Reply Brief. Appeal 2021-000539 Application 14/360,503 2 STATEMENT OF THE CASE Appellant’s disclosure relates to “relates to a delivery device for drugs or other agents, to methods of making and using the delivery device, and to the treatment of cancer” (Spec. ¶ 2). Appellant’s only independent claim, claim 1, is reproduced below: 1. A delivery system comprising nanoparticles comprising a mass of crosslinked and functionalized starch biopolymers, wherein the starch biopolymers comprise glucose repeating units and carboxyl groups; and, amine modified aptamer targeting molecules directly linked to the carboxyl groups of the nanoparticles, wherein the aptamer targeting molecules are attached to the nanoparticles in an amount sufficient to provide a molar ratio of the glucose repeating units to the targeting molecules within a range from about 100:1 to less than 1000:1. (Appeal Br. 13.) Claims 1, 3, 6–9, and 34–37 stand rejected under 35 U.S.C. § 103(a) as unpatentable over the combination of Giezen,3 Xiao,4 Fishman,5 and Aravind.6 3 Giezen et al., US 6,677,386 B1, issued Jan. 13, 2004. 4 Xiao et al., Preparation of folate-conjugated starch nanoparticles and its application to tumor-targeted drug delivery vector, 51 CHINESE SCIENCE BULLETIN 1693–97 (2006). 5 Marshall L. Fishman et al., Molar Masses and Sizes of Starches by High- Performance Size-Exclusion Chromatography with On-Line Multi-Angle Laser Light Scattering Detection, 44 J. AGRIC. FOOD CHEM. 3182–3188 (1996). 6 Athulya Aravind et al., Aptamer-labeled PLGA nanoparticles for targeting cancer cells, 3 CANCER NANO 1–12 (2012). Appeal 2021-000539 Application 14/360,503 3 ISSUE Does the preponderance of evidence relied upon by Examiner support a conclusion of obviousness? FACTUAL FINDINGS (FF) FF 1. Giezen “relates to a process for producing nanoparticles, i.e. particles essentially consisting of a biopolymer such as starch” and “to nanoparticles obtainable by such a process” (Giezen 1:5–8; see Final Act.7 4; see also Final Act. 6 (Examiner finds that starch “is a polymer of repeating glucose units”)). FF 2. Giezen discloses “that [its] biopolymers such as starch . . . may be previously modified, e.g. with[, inter alia,] carboxy-methyl groups” (Giezen 1:13–19; see Final Act. 4; see also Appeal Br. 7 (Appellant concedes that “a carboxymethyl group could be considered a type of carboxyl group”)). FF 3. Giezen discloses that its nanoparticles can be used as “carriers e.g. in medicines, where they may be complexed or covalently coupled to active substances” (Giezen 3:8–11; see Final Act. 4). FF 4. Examiner finds that Giezen does not disclose that its “starch nanoparticles are conjugated to . . . [an] aptamer at a ratio of glucose units to aptamer of about 100:1 to about 500:1” (Final Act. 5). FF 5. Xiao discloses the conjugation of PEG modified folate (FA-PEG) to the surface of starch nanoparticles (StNP) “to obtain . . . folate-conjugated starch nanoparticles . . . a potentially useful system [for] . . . the targeted delivery of anticancer drug DOX” (Xiao, Abstr.; see also id. at 1693 (Xiao discloses that “[f]olate displays extremely high affinity to its receptor, which 7 Examiner’s August 16, 2018, Final Office Action. Appeal 2021-000539 Application 14/360,503 4 enables them to rapidly bind to the FR and become internalized via an endocytic process”); Final Act. 4). FF 6. Xiao discloses the “[p]reparation of FA-PEG/StNP,” wherein 1 mg of StNP was suspended in 1 mL of distilled water, and 0.1 mg of FA-PEG-NH2 was added to the StNP solution, shaking for 3 h under room temperature. The solution was centrifuged and washed twice with PBS (pH 7.4), and the precipitate was lyophilized. 1 mg of the lyophilized product was suspended in 1 mL of distilled water, and then treated with a-amylase for 2 h in 37°C with shaking to digest starch. The concentration of FA in digested solution was detected by UV spectrophotometer at 363 nm, while there is no absorbance of other materials in solution under this wavelength. Serially distilled water-diluted folate was used to construct a calibration curve. (Xiao § 1.2(iii); see also id. § 2.3 (Xiao discloses that “[t]he FA modified concentration in FA-PEG/StNP was 0.8 μg/mg detected by UV spectrophotometer at 363 nm. This indicated that activated folate was coupled to StNP successfully.”).) FF 7. Examiner relies on Fishman to “disclose that ‘starch’ has an average molecular weight on the order of about 106 g/mol, for example about 2 X 106 g/mol for presolubilized potato starch” (Final Act. 4 (citing Fishman, Table 6)). FF 8. Aravind discloses “[a]ptamer-labeled [poly(lactic-co-glycolic acid (PLGA)] nanoparticles for targeting cancer cells” (Aravind, Title; see also id., Abstr.; id. at 3 (Aravind discloses that “[a]mine-modified AS1411 aptamer was conjugated on the carboxyl group carrying nanoparticles using the common conjugation strategy of carbodiimide chemistry (cross-linking of the carboxylic acid group on the nanoparticle surface and the amine group of the aptamer to form an amide linkage)”); see generally Final Act. 4). Appeal 2021-000539 Application 14/360,503 5 FF 9. Aravind discloses that conjugation of the AS1411, tumor cell targeting, aptamer onto PLGA nanoparticles loaded with the anti-cancer drug paclitaxel (PTX) enhanced the anti-tumor efficacy of the PTX-PLGA nanoparticle compared to non-targeted PTX-PLGA nanoparticles (Aravind 2; see generally Final Act. 4). ANALYSIS The combination of Giezen, Xiao, Fishman, and Aravind establishes that, prior to Appellant’s effective filing date, those of ordinary skill in this art recognized that starch and PLGA were both useful in producing nanoparticle drug delivery vehicles or carriers (see FF 1–9). This prior art further establishes that, prior to Appellant’s effective filing date, those of ordinary skill in this art recognized that the foregoing nanoparticles can comprise targeting molecules, such as folate and aptamer, i.e. AS1411, to effectively target a nanoparticle to a desired location (id.). The prior art relied upon by Examiner also directs those of ordinary skill in this art to functionalize the nanoparticle with, for example, carboxy-methyl groups, which Appellant concedes is a type of “carboxyl group” (see FF 2) and attach the targeting molecule, i.e. amine-modified AS1411 aptamer, to the carboxyl group on the nanoparticle (see, e.g., FF 8). Thus, we find no error in Examiner’s conclusion that the combination of Giezen, Xiao, Fishman, and Aravind, makes obvious a delivery system comprising nanoparticles comprising a mass of crosslinked and functionalized starch biopolymers, wherein the starch biopolymers comprise glucose repeating units and carboxyl groups; and, amine modified aptamer targeting molecules directly linked to the carboxyl groups of the nanoparticles (see FF 1–9; see also Final Act. 8 (“Examiner concludes that Appeal 2021-000539 Application 14/360,503 6 the subject matter defined by the instant claims would have been obvious within the meaning of . . . [35 U.S.C. §] 103(a), especially in the absence of evidence to the contrary”)). Appellant’s independent claim 1, however, further requires that “the aptamer targeting molecules are attached to the nanoparticles in an amount sufficient to provide a molar ratio of the glucose repeating units to the targeting molecules within a range from about 100:1 to less than 1000:1” (Appeal Br. 13). Recognizing this requirement of Appellant’s claimed invention, Examiner reasons that because Fishman disclose[s] that the average molecular weight of presolubilized starch is on the order of about 2 X 106 g/mol, and . . . [because] one of ordinary skill in the art would know that the molecular weight of a single glucose unit is about 180 g/mol, it follows that there are on average about 2 X 106/180, or about 11,000, glucose repeating units per starch molecule. (Final Act. 6.) Examiner further reasons that Xiao disclose[s] targeting molecule conjugated crosslinked starch nanoparticles in which 1 mg of starch is combined with 0.1 mg of targeting molecule, e.g. FA-PEG-NH2, and that the PEG-bis (amino) they employ has a molecular weight of 3350 g/mol . . ., making the molecular weight of FAPEG-NH2 about 3800 g/mol from the sum of the molecular weight of folate, which one of ordinary skill in the art would know is about 442 g/mol, and the molecular weight of PEG-bis (amino). (Id. (citing Xiao § 1.1).) Examiner then explains that when formulating a starch nanoparticle to comprise a targeting molecule, e.g., folate, those of ordinary skill in this art would understand “that there are about 6.022 X 1023 (Avogadro’s number) starch molecules per mole and likewise about 6.022 X Appeal 2021-000539 Application 14/360,503 7 1023 FA-PEG-NH2 molecules per mole” (id. at 6–7). Thus, Examiner concludes that factoring in the 11,000 glucose repeating units per starch molecule . . ., one of ordinary skill in the art would reasonably expect that Xiao’s folate conjugated starch nanoparticles will have a ratio of glucose repeating units to the targeting ligand of about 212 glucose repeating units per targeting ligand; i.e. a ratio of 212:1, well within [Appellant’s] claimed range of about 100:1 to about 500:1. (Id. at 7.) Although the forgoing analysis based on Xiao relates to a folate targeting molecule rather than an aptamer, as is required by Appellant’s claimed invention, Examiner appears to take the position that there is no reason to expect that a different targeting molecule would require a different molar ratio of glucose repeating units to targeting molecules, or that such an effective molar ratio could not be obtained through routine optimization using Xiao’s ratio as a starting point (see generally Ans.8 8–9). We are not persuaded. As Appellant explains, “the folate to glucose ratio calculated in the Office Action is improperly based on a combination of 1 mg of starch and 0.1 mg of FA-PEG-NH2,” which are the “amounts introduced at the start of the reaction” to produce nanoparticles, rather than the amounts present in the final nanoparticle produced in the reacted reagents (see Appeal Br. 9–10; Reply Br. 8 (“Applicant submits that the Examiner’s calculation is based on amounts of folate and starch added to a reactor but with no evidence that they reacted in those same amounts.”); see also FF 6). As Xiao makes clear, the FA concentration in its final nanoparticle preparation was 0.8 μg/mg 8 Examiner’s December 20, 2019, Answer. Appeal 2021-000539 Application 14/360,503 8 (FF 6). Thus, using the amount of folate conjugated to the final nanoparticle, “the molar ratio of glucose repeating units to folate attached to the nanoparticles in [Xiao’s final nanoparticle preparation] is about 3000:1,” which “is . . . numerically far outside of the claimed range of about 100:1 to less than 1000:1” (Appeal Br. 9–10; see generally id. at 10–11). In view of the foregoing, we are not persuaded by Examiner’s assertion that Xiao’s starting amounts of folate and starch should be used to calculate the molar ratio required by Appellant’s claimed invention rather than the amounts present in the final product (see Ans. 9–11). To the contrary, we find that Examiner failed to establish an evidentiary basis on this record to support a conclusion that the combination of Giezen, Xiao, Fishman, and Aravind makes obvious the subject matter of Appellant’s claimed invention. CONCLUSION The preponderance of evidence relied upon by Examiner does not support a conclusion of obviousness. The rejection of claims 1, 3, 6–9, and 34–37 under 35 U.S.C. § 103(a) as unpatentable over the combination of Giezen, Xiao, Fishman, and Aravind is reversed. DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 3, 6–9, 34–37 103(a) Giezen, Xiao, Fishman, Aravind 1, 3, 6–9, 34–37 REVERSED Copy with citationCopy as parenthetical citation