Wisconsin Alumni Research Foundation

Patent Trials and Appeals Board

Jan 28, 2022

2021002154 (P.T.A.B. Jan. 28, 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. 14/871,327 09/30/2015 William L. Murphy P150078US01 (3004049-0033 1671 130832 7590 01/28/2022 Stinson LLP (WARF 3004049) 7700 Forsyth Blvd. Suite 1100 St. Louis, MO 63105 EXAMINER DINES, KARLA A ART UNIT PAPER NUMBER 1639 NOTIFICATION DATE DELIVERY MODE 01/28/2022 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): USpatent2@stinson.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte WILLIAM L. MURPHY, ANDREW SALIM KHALIL, XIAOHUA YU, KRISHANU SAHA, JARED MATTHEW CARLSON-STEVERMER, and BENJAMIN GABRIEL STEYER1 Appeal 2021-002154 Application 14/871,327 Technology Center 1600 Before ERIC B. GRIMES, TAWEN CHANG, and JOHN E. SCHNEIDER, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134(a) involving claims related to methods of non-viral cell transfection, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 Appellant identifies the real party in interest as Wisconsin Alumni Research Foundation. Appeal Br. 1. “Appellant” refers to “applicant” as defined in 37 C.F.R. § 1.42. Appeal 2021-002154 Application 14/871,327 2 STATEMENT OF THE CASE “[T]he present disclosure relates to methods of using biodegradable mineral coatings for non-viral cell transfection.” Spec. ¶ 3. “The mineral coatings bind biomaterials (e.g., polynucleotides) and provide a source of calcium and phosphate ions for transfection of cells.” Id. ¶ 6. Claims 1, 2, 4-10, and 12-22 are on appeal. Claim 1, reproduced below, is illustrative: 1. A method of non-viral transfection comprising: preparing a mineral coated microparticle, wherein the mineral coated microparticle comprises a mineral coating formed by incubating a microparticle substrate in a simulated body fluid, wherein the simulated body fluid comprises from about 5 mM to about 12.5 mM calcium ions, from about 2 mM to about 12.5 mM phosphate ions, from about 4 mM to about 100 mM carbonate ions, and a pH of from about 4 to about 7.5 and halogen ions; contacting the mineral coated microparticle with a biomaterial, wherein the biomaterial binds the mineral coating; contacting a cell with the mineral coated microparticle; and culturing the cell. Appeal Br. 29 (Claims Appendix). Appeal 2021-002154 Application 14/871,327 3 The claims stand rejected as follows: Claims 1, 2, 4, and 6-8 under 35 U.S.C. § 103(a) as obvious based on Choi,2 Goldstein,3 Kovtun,4 Lee,5 and Chowdhury6 (Non-Final Action7 5); Claim 5 under 35 U.S.C. § 103(a) as obvious based on Choi, Goldstein, Kovtun, Lee, Chowdhury, and Dobson8 (Non-Final Action 12); Claim 9 under 35 U.S.C. § 103(a) as obvious based on Choi, Goldstein, Kovtun, Lee, Chowdhury, and Hannon9 (Non-Final Action 13); Claims 10, 12, 15, and 21 under 35 U.S.C. § 103(a) as obvious based on Choi, Goldstein, Kovtun, Lee, and Chowdhury (Non-Final Action 14); Claims 13 and 14 under 35 U.S.C. § 103(a) as obvious based on Choi, Goldstein, Kovtun, Lee, Chowdhury, and Dobson (Non-Final Action 18); Claims 16-18 and 22 under 35 U.S.C. § 103(a) as obvious based on Choi, Goldstein, Kovtun, Lee, and Chowdhury (Non-Final Action 19); and Claims 19 and 20 under 35 U.S.C. § 103(a) as obvious based on Choi, Goldstein, Kovtun, Lee, Chowdhury, and Dobson (Non-Final Action 22). 2 Sustained plasmid DNA release from dissolving mineral coatings, NIH-PA Author Manuscript 1-21, published in final edited form as: ACTA BIOMATER. 6(9):3426-3435 (2010). 3 US 6,143,037, issued November 7, 2000. 4 Calcium phosphate nanoparticles for the transfection of cells, BIO- MEDICAL MAT. AND ENGINEERING 19:241-247 (2009). 5 Nano-sized calcium phosphate (CaP) carriers for non-viral gene delivery, MATERIALS SCI. AND ENGINEERING B 177:289-302 (2012). 6 Fluoride enhances transfection activity of carbonate apatite by increasing cytoplasmic stability of plasmid DNA, BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS 409:745-747 (2011). 7 Office Action mailed August 8, 2019. 8 US 2008/0286361 A1, published November 20, 2008. 9 US 2008/0025958 A1, published January 31, 2008. Appeal 2021-002154 Application 14/871,327 4 OPINION Obviousness based on Choi, Goldstein, Kovtun, Lee, and Chowdhury Claims 1, 2, 4, 6-8, 10, 12, 15-18, 21, and 22 stand rejected based on Choi, Goldstein, Kovtun, Lee, and Chowdhury. The Examiner finds that Choi teaches that “calcium phosphate mineral coatings may be a useful platform for plasmid DNA delivery.” Non-Final Action 5. The Examiner finds that Choi’s “mineral coating is formed by incubating a substrate in a simulated body fluid” in which the concentrations of calcium, phosphate, and carbonate ions, as well as the pH, overlap the ranges recited in claim 1. Id. at 5-6. The Examiner also finds that Choi teaches incubating its mineral- coated film with plasmid DNA to allow binding. Id. at 6. The Examiner finds that Choi does not teach a microparticle substrate for its mineral coating, but Goldstein teaches that “polymeric microspheres and/or nanospheres are widely used as a vehicle for delivering drugs” and have the “ability to enter cells and penetrate intracellular junctions.” Id. at 7- 8. The Examiner also finds that Kovtun “teach[es] calcium phosphate coated nanoparticles functionalized with nucleic acids and . . . the use of the nanoparticles in in vitro cell culture.” Id. at 8. The Examiner finds that Kovtun teaches that such nanoparticles “represent an easy, cost-effective, nontoxic and efficient method of transfection.” Id. “In the same vein, Lee et al. teach nano-sized calcium phosphate carriers for non-viral gene delivery.” Id. The Examiner finds that “Chowdhury teaches a dramatic enhancement of transgene expression by inclusion of a halogen, fluoride, in the formation of carbonate apatite.” Id. Appeal 2021-002154 Application 14/871,327 5 The Examiner concludes that it would have been obvious “to have modified the method taught by Choi et al. . . . to use a nanoparticle as the substrate instead of the two-dimensional polymer substrate taught by Choi et al. because Goldstein et al. taught the advantages of using a microsphere or nanoparticle in transfection.” Id. at 8-9. The Examiner also reasons that it would have been obvious “to combine Choi et al. and Goldstein et al. with the method of using microparticles and/or nanoparticles comprising a mineral coating because Kovtun et al. taught the use of calcium phosphate coated nanoparticles for transfection. Likewise, Lee et al. teach nano-sized calcium phosphate carriers for non-viral gene delivery.” Id. at 9. Finally, the Examiner concludes that it would have been obvious to “us[e] a halogen ion because Chowdhury teaches that there was a dramatic enhancement of transgene expression by inclusion of fluoride in the formation of carbonate apatite.” Id. at 10. We agree with the Examiner that the cited references would have made obvious the method of Appellant’s claim 1. Choi teaches that “[c]alcium phosphate (CaP) minerals . . . [have the] well-characterized ability . . . to bind and release plasmid DNA,” which “provides a potential mechanism for controlled release of plasmid DNA from various biomaterials.” Choi 1, abstract.10 Choi states that “investigators have grown 10 Choi was cited in an Information Disclosure Statement filed April 11, 2013 in application 13/769,993 (of which the instant application is a continuation-in-part). The copy of Choi filed with the IDS is an Author Manuscript with pages numbered 1-21, not the final edited version (with pages 3426-3435). Our citations are to the Author Manuscript that is in the record. Appeal 2021-002154 Application 14/871,327 6 ‘bone-like’ CaP mineral coatings on polymers, ceramics, and metals using a simulated body fluid (SBF), which has a pH and ion concentrations similar to human blood plasma.” Id. at 2, first paragraph (citations omitted) Choi teaches that poly(lactide-co-glycolide) (PLG) was dissolved and dried into films, then incubated in various mineral solutions, “resulting [in] mineral-coated PLG films.” Id. at 3, last paragraph. Choi’s Table 1 is reproduced below: Table 1 shows “[i]on concentrations of human blood plasma and SBF solutions.” Id. at 21, Table 1 heading. More specifically, Table 1 shows that Choi’s 2x SBF, 3.5x SBF, and 5x SBF solutions contained 5-12.5 mM calcium ions (Ca2+), 2.0-5.0 mM phosphate ions (HPO42-), and 4.2 mM carbonate ions (HCO3-), all of which are within the ranges for these ions in claim 1. Table 1 also shows that these solutions had a pH of 6.0-6.8, within the range recited in claim 1, and contained 157-172 mM chloride ions (Cl-), which are halogen ions. Thus, Choi teaches forming a mineral coating on a PLG substrate by incubating the substrate in a simulated body fluid meeting all of the limitations of claim 1.11 Choi also teaches “[m]ineral-coated PLG films were 11 The Examiner finds that Choi does not teach a simulated body fluid containing halogen ions (Non-Final Action 8), but Choi’s SBF solutions Appeal 2021-002154 Application 14/871,327 7 incubated in 1[ ]ml of preparation buffer . . . containing 20 μg of pDNA [plasmid DNA] for 1 d to allow for binding.” Id. at 4, third paragraph. Choi therefore teaches contacting its mineral-coated substrate with a biomaterial that binds the mineral coating, as recited in claim 1. Finally, Choi states that “[t]hese results indicate that the release rate of pDNA could be tailored by varying the properties of the solution environment. . . . Therefore, these Ca-P mineral coatings may be a useful platform for pDNA delivery applications in future studies.” Id. at 9, first paragraph. See also id. at 3, first partial paragraph (Previous workers observed that “PEI/DNA complexes immobilized on PLG disks transfected cells at significantly lower dosage when compared with transfection using bolus delivery.”). Thus, Choi also makes obvious the steps of contacting a cell with its mineral-coated substrate and culturing the cell, as recited in claim 1. As the Examiner noted, Choi does not teach microparticles. Goldstein, Kovtun, and Lee, however, make up for this deficiency. Goldstein states that it is often desirable to deliver pharmaceutical agents (including DNA) intracellularly, and “[m]icrospheres and/or nanospheres are a widely used vehicle for delivering drugs intracellularly.” Goldstein 2:59-65, 3:1-2. Goldstein states that microspheres generally “comprise a biodegradable polymeric core having a pharmaceutical agent incorporated therein. Microspheres are typically spherical and have an contain chloride ions (Cl-), and chlorine is a halogen. Therefore, Chowdury’s disclosure is not necessary for a finding of obviousness with respect to claim 1. Appeal 2021-002154 Application 14/871,327 8 average diameter of about 1 to 900 μm.” Id. at 3:2-6. Goldstein also states that the advantages of microspheres include “their ability to enter cells and penetrate intracellular junctions.” Id. at 3:9-11. Kovtun discloses that “[s]ingle-shell and multi-shell calcium phosphate nanoparticles were prepared and functionalized with DNA. . . . The transfection efficiency of the nanoparticles was tested in vitro in cell culture.” Kovtun 241, abstract. Kovtun’s single-shell “nanoparticles consist of a calcium phosphate core and an outer shell of nucleic acid.” Id. at 243, § 3.1. “To enhance the DNA protection against attack of nuclease, the single-shell nanoparticles were modified by the addition of additional layers of calcium phosphate (for protection) and nucleic acid (for electrosteric stabilization),” for form triple-shell nanoparticles. Id. Kovtun’s Figure 2 is reproduced below: Figure 2 shows a “schematic representation of . . . single-shell (A) and triple-shell (B) calcium phosphate nanoparticles, functionalized with nucleic acids.” Kovtun 244, Fig. 2 legend. Kovtun’s Figure 3 is reproduced below: Appeal 2021-002154 Application 14/871,327 9 Figure 3 shows “the results of transfection experiments.” Id. at 244. More specifically, Figure 3 shows the transfection efficiency using single- shell or triple-shell nanoparticles, compared to the classical calcium phosphate precipitation method and Polyfect®, a “commercial transfection agent.” Id. at 243. The approximate transfection efficiencies were 2.5% for the classical method, 3.5% for single-shell nanoparticles, and 10% for both triple-shell nanoparticles and Polyfect®. Lee reviews “current research activity in the development of CaP based ceramic and polymer-ceramic hybrid systems for non-viral gene delivery.” Lee 289, abstract. Lee states that “[n]anostructured calcium phosphate materials have been identified as potentially useful bioceramics for . . . gene delivery” and “calcium phosphate is superior to other gene delivery methods in terms of safety ( e.g. immunogenicity, toxicity, etc.).” Id. at 300, left col. Based on these teachings, it would have been obvious to modify Choi’s method by binding DNA to mineral-coated PLG microparticles, rather than mineral-coated PLG films. Motivation to do so is provided by Goldstein, Kovtun, and Lee. Specifically, Goldstein teaches that it is desirable to deliver drugs, including DNA, intracellularly, and microspheres Appeal 2021-002154 Application 14/871,327 10 are widely used for doing so. Goldstein 2:59 to 3:6. Kovtun teaches that both single-shell and triple-shell CaP nanoparticles, functionalized with DNA, provided higher transfection efficiency than the classical calcium phosphate (CaP) precipitation method. Kovtun, Fig. 3. And Lee teaches that calcium phosphate is safer than other gene delivery methods. Thus, it would have been obvious to use PLG microparticles in Choi’s method of gene delivery in order to achieve intracellular delivery of DNA safely and with a higher transfection efficiency than that provided by the classical CaP precipitation method. Appellant argues that “one skilled in the art would not modify Choi . . . to apply its mineral coatings onto microparticles.” Appeal Br. 9. Specifically, Appellant argues that “to coat the microspheres/nanospheres of Goldstein with the mineral coating of Choi . . . would require doing the opposite of the teachings in Goldstein, which is to incorporate the active agent in the core of the microspheres/nanospheres.” Id. at 10. Appellant also argues that “Lee describes the co-precipitation of Ca-P and DNA particles, resulting in nanoparticles with internalized DNA. Kovtun describes nanoparticles comprising Ca-P coated with either (a) a single layer of DNA or (b) multiple layers of DNA/Ca-P. . . . Thus, these . . . references also teach incorporating DNA within their nanoparticles.” Id. at 11. Similarly, Appellant argues that “that one skilled in the art would not have a reasonable expectation of success that the references could be modified to arrive at mineral coated microparticles with a biomaterial bound to the mineral coating for the purpose of cell transfection” based on the cited references. Id. at 13. Appellant argues that “Kovtun . . . found that particles containing encapsulated DNA were far superior to nanoparticles with Appeal 2021-002154 Application 14/871,327 11 exposed DNA” and “Goldstein discloses that microparticles contained in a polymer matrix were incorporated by cells better than freely applied microparticles.” Id. at 14.12 These arguments are unpersuasive. The Examiner’s rejection is not premised on combining Choi’s teachings with Goldstein’s method of making microspheres with encapsulated DNA. The Examiner notes that Goldstein “is silent concerning mineral coated microspheres.” Non-Final Action 8. The Examiner cites Goldstein as evidence that “polymeric microspheres and/or nanospheres are widely used as a vehicle for delivering drugs.” Id. at 7. In addition, the evidence of record does not support Appellant’s assertion that Kovtun and Lee “teach incorporating DNA within their nanoparticles.” Appeal Br. 11. Kovtun’s Figure 3 is reproduced above, and shows that both its single-shell and triple-shell nanoparticles have an outer layer of DNA. It is true that the triple-shell nanoparticles work best, but even the single-shell nanoparticles provide a level of transfection efficiency that is higher than that of the classical calcium phosphate precipitation method. See Kovtun’s Figure 3, reproduced above. Lee states that “[c]alcium phosphates have been used as gene carriers for more than 30 years by way of DNA- calcium phosphate co-precipitation as an efficient method to introduce pDNA into cells.” Lee 294, right col. Thus, Kovtun’s single-shell 12 Appellant also presents an argument based on “(Choi, p. 1, first paragraph)” and “(id. at second paragraph).” Appeal Br. 13-14. However, page 1 of Choi includes only a single paragraph (“Abstract”), and the first two paragraphs on Choi’s page 2 are part of its background discussion (“Introduction”), and in any case do not support Appellant’s assertions regarding its disclosure. Appeal 2021-002154 Application 14/871,327 12 nanoparticles appear to provide an acceptable level of transfection efficiency. For its part, Lee states that “the formation of pDNA-CaP complexes via the coprecipitation method” proceeds via calcium ions binding to the anionic pDNAs to form Ca-pDNA complexes, which then react with phosphate (PO43-) anions to “form CaP-pDNA complexes by precipitation as the pDNAs are condensed into and around the calcium phosphate particulates.” Lee 296, Fig. 7 legend (emphasis added). Thus, Lee also does not support Appellant’s position that it describes DNA incorporated within its particles. With respect to a reasonable expectation of success, Kovtun discloses that its single-shell nanoparticles, with DNA as the outer layer, provide better transfection efficiency than the classical calcium phosphate precipitation method, and Lee discloses that calcium phosphate co- precipitation has been used for over 30 years as an efficient method of transfection. Based on these teachings, a skilled artisan would have had a reasonable expectation of success in modifying Choi’s method to use mineral-coated PLG microparticles, having an outer layer of DNA, for cell transfection. With respect to claim 21, Appellant argues that it “specifically requires that the microparticle substrate have a particle size orders of magnitude higher than that recommended by Lee.” Appeal Br. 19. This argument is unpersuasive because, as the Examiner has found “Goldstein et al. teach a microsphere has an average diameter of about 1 to 900 μm; e.g. col. 3, lines 5-6.” Non-Final Action 18. Goldstein also teaches that “[m]icrospheres . . . are a widely used vehicle for delivering drugs Appeal 2021-002154 Application 14/871,327 13 intracellularly.” Goldstein 3:1-2. Thus, Goldstein (not Lee) provides a reason to use microparticles in the size range recited in claim 21 in Choi’s method, in place of Choi’s PLG film. In summary, we affirm the rejection of claims 1 and 21 under 35 U.S.C. § 103(a) based on Choi, Goldstein, Kovtun, Lee, and Chowdhury. Appellant presents no additional substantive argument with respect to claims 2, 4, 6-8, 10, 12, 15-18, and 22. Appeal Br. 16, 19-20, 23-24. Therefore, those claims fall with claims 1 and 21. 37 C.F.R. § 41.37(c)(1)(iv). Obviousness based on Choi, Goldstein, Kovtun, Lee, Chowdhury, and Dobson Claims 5, 13, 14, 19, and 20 stand rejected based on Choi, Goldstein, Kovtun, Lee, Chowdhury, and Dobson. Claims 5, 13, and 19 require the microparticle to comprise a magnetic material, and claims 14 and 20 list specific types of magnetic materials. The Examiner relies on Choi, Goldstein, Kovtun, Lee, and Chowdhury for the same disclosures discussed above, and finds that Dobson teaches “nanoparticles comprising magnetite used for transfection of cells.” Non-Final Action 12. The Examiner concludes that it would have been obvious to modify the method made obvious by Choi, Goldstein, Kovtun, Lee, and Chowdhury “with the inclusion of a particle comprising a magnetic material . . . because Dobson et al. teach an improved uptake of the particle by the transfected particle.” Id. See also id. at 19, 23. We agree with, and adopt, the Examiner’s findings and conclusion. Appeal 2021-002154 Application 14/871,327 14 Appellant argues that claims 5, 13, 14, 19, and 20 are patentable for the same reasons that claim 1 is patentable. Appeal Br. 17, 21-22, 25. This argument is unpersuasive for the reasons discussed above. With regard to claim 5, Appellant also argues that the Examiner has again identified an element recited in the claimed invention and merely identified a reference disclosing that element. In particular, claim 5 recites incorporating a magnetic material into a mineral coated microparticle. The Examiner has simply identified Dobson for disclosing magnetic particles and concluded that it would be obvious to one skilled in the art to combine Dobson with Choi, Goldstein, Lee, Kovtun, and Chowdhury. Id. at 17. Similarly, with regard to claims 19 and 20, Appellant argues that the combination of Choi, Goldstein, Lee, Kovtun, Chowdhury and Dobson fails to disclose or suggest a fluoride-doped mineral coated microparticle comprising at least one mineral coating surrounding a surface of a microparticle substrate, the at least one mineral coating comprising calcium, phosphate, and fluoride ions, and further comprising a magnetic material comprising at least one of magnetite, magnetite-doped plastics, and neodymium, as recited in claims 19 and 20. Id. at 25-26. These assertions do not constitute separate arguments with respect to claims 5, 19, and 20. With respect to claim 5, Appellant asserts that the Examiner found the claim’s additional limitation in the prior art and concluded that it would have been obvious to combine it with the teachings of the other references, but Appellant does not assert any error in the Examiner’s finding or conclusion. Appellant therefore has not identified any error in the rejection of claim 5. Appeal 2021-002154 Application 14/871,327 15 With respect to claims 19 and 20, Appellant’s position amounts to stating that the references do not disclose or suggest the claimed invention, without any supporting reasoning. Appellant therefore has not identified any error in the rejection of claims 19 and 20. See In re Huai-Hung Kao, 639 F.3d 1057, 1065 (Fed. Cir. 2011) (Statements in a brief that “merely mention [a] claim . . . and lack any type of separate, substantive argument concerning the claim” do not constitute separate argument regarding that claim). Obviousness based on Choi, Goldstein, Kovtun, Lee, Chowdhury, and Hannon Claim 9 stands rejected as obvious based on Choi, Goldstein, Kovtun, Lee, Chowdhury, and Hannon. Claim 9 requires that the cell is selected from one of three cell types. The Examiner relies on Choi, Goldstein, Kovtun, Lee, and Chowdhury for the same disclosures discussed above, and finds that Hannon teaches “introducing nucleic acids into cells,” including mesenchymal stem cells, and teaches “the advantages of mesenchymal stem cells.” Non-Final Action 13. The Examiner concludes that it would have been obvious to modify the method made obvious by Choi, Goldstein, Kovtun, Lee, and Chowdhury with the inclusion of using mesenchymal stem cells . . . because Hannon et al. teaches that mesenchymal stem cells (MSCs), which are readily isolated, have a broader differentiation potential than previously recognized; . . . and mesenchymal stem cells were known to be transfectable by means of calcium phosphate at the time of the invention. Id. at 14. We agree with, and adopt, the Examiner’s findings and conclusion. Appeal 2021-002154 Application 14/871,327 16 Appellant argues that “[c]laim 9 . . . is patentable over the combination of Choi, Goldstein, Lee, Kovtun, Chowdhury and Hannon for at least the same reasons provided for claim 1.” Appeal Br. 18. This argument is unpersuasive for the reasons discussed above. Appellant also argues that the Examiner has again identified an element recited in the claimed invention and merely identified a reference disclosing that element. In particular, claim 9 recites cell types that can be used in the method of claim 1. The Examiner has simply identified Hannon for disclosing cell types recited in claim 9 and concluded that it would be obvious to one skilled in the art to combine Hannon with Choi, Goldstein, Lee, Kovtun, and Chowdhury. Id. Again, Appellant asserts that the Examiner found the claim 9’s additional limitation in the prior art and concluded that it would have been obvious to combine it with the teachings of the other references, but Appellant does not assert any error in the Examiner’s finding or conclusion. Appellant therefore has not identified any error in the rejection of claim 9. Appeal 2021-002154 Application 14/871,327 17 DECISION SUMMARY In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 2, 4, 6-8 103(a) Choi, Goldstein, Kovtun, Lee, Chowdhury 1, 2, 4, 6-8 5 103(a) Choi, Goldstein, Kovtun, Lee, Chowdhury, Dobson 5 9 103(a) Choi, Goldstein, Kovtun, Lee, Chowdhury, Hannon 9 10, 12, 15, 21 103(a) Choi, Goldstein, Kovtun, Lee, Chowdhury 10, 12, 15, 21 13, 14 103(a) Choi, Goldstein, Kovtun, Lee, Chowdhury, Dobson 13, 14 16-18, 22 103(a) Choi, Goldstein, Kovtun, Lee, Chowdhury 16-18, 22 19, 20 103(a) Choi, Goldstein, Kovtun, Lee, Chowdhury, Dobson 19, 20 Overall Outcome 1, 2, 4-10, 12-22 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). See 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED