PHOSPHOREX, INC.

Patent Trials and Appeals Board

Feb 17, 2022

2021003073 (P.T.A.B. Feb. 17, 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. 14/916,439 03/03/2016 Bin Wu 4246.1003 US1 1805 38473 7590 02/17/2022 ELMORE PATENT LAW GROUP, PC 484 Groton Road Westford, MA 01886 EXAMINER GREENE, IVAN A ART UNIT PAPER NUMBER 1619 NOTIFICATION DATE DELIVERY MODE 02/17/2022 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@elmorepatents.com pair_elmore@firsttofile.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE ____________ BEFORE THE PATENT TRIAL AND APPEAL BOARD ____________ Ex parte BIN WU ____________ Appeal 2021-003073 Application 14/916,4391 Technology Center 1600 ____________ Before TAWEN CHANG, RACHEL H. TOWNSEND, and DAVID COTTA, Administrative Patent Judges. COTTA, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a method for preparing PLGA microparticles or nanoparticles having negative surface charges. The Examiner rejected the claims on appeal under 35 U.S.C. § 102 as anticipated, under 35 U.S.C. § 103 as obvious, and on the ground of double patenting. An oral hearing was held on November 15, 2021, a transcript from which has been entered into the record. We affirm-in-part. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. According to Appellant, the real party in interest is Phosphorex, Inc. Appeal Br. 1. Appeal 2021-003073 Application 14/916,439 2 STATEMENT OF THE CASE The Specification discloses that “[c]ertain carboxylated particles, such as carboxylated polystyrene, PLGA, or diamond particles, when administered to subjects, may ameliorate certain conditions, such as pathological inflammatory immune responses.” Spec. 1. However, according to the Specification, “carboxylated PLGA particles produced using conventional means are frequently not biocompatible and thus PLGA particles resulting from such manufacturing processes may not be safe for use on humans and animals.” Id. Further “PLGA particles produced using conventional means may not contain sufficient number of COOH groups for attaching API’s or other chemical entities to microparticles and nanoparticles.” Id. Accordingly, the Specification teaches that there is “a need to prepare negatively charged (e.g., carboxylated PLGA) microparticles and nanoparticles with enhanced therapeutic properties.” Id. The Specification discloses “a method for the preparation of a composition comprising microparticles or nanoparticles having negative surface charges, said method comprising producing said microparticles or nanoparticles with a pharmaceutically acceptable polymer using either an emulsion process or a precipitation process.” Id. at 2. The method disclosed “provides polymer particles (microparticles and nanoparticles) which contain unusually high or at least increased negative charges on the surface of said particles compared to those produced using conventional methods.” Id. at 7. Appeal 2021-003073 Application 14/916,439 3 Claims 44-59, 61-75, and 77-85 are on appeal. Claim 44 is representative and reads as follows: 44. A method for preparing PLGA microparticles or nanoparticles having negative surface charges, said method comprising: (1) dissolving a pharmaceutically acceptable negatively charged agent selected from a water-soluble polymer in a first aqueous solvent to form a first aqueous solution having a pH that promotes ionization of the PLGA and the pharmaceutically acceptable negatively charged agent; (2) dissolving a pharmaceutically acceptable PLGA polymer in an organic solvent to form a polymer solution, wherein the organic solvent is not miscible or is partially miscible in the first aqueous solvent; (3) emulsifying the polymer solution in the first aqueous solution to form an emulsion; and (4) removing the organic solvent to form said PLGA microparticles or nanoparticles having negative surface charges; wherein the microparticles or nanoparticles have a zeta potential of from about -15 mV to about -100 mV. Appeal Br. 46. The claims stand rejected as follows: Claims 44-47, 49-55, 57, 58, 61-65, 67-71, 73-75, 77-81, 83, and 84 were rejected under 35 U.S.C. § 102(b) as anticipated by Vandervoort2 as evidenced by Szente3 and Varges.4 2 Vandervoort et al., Biocompatible stabilizers in the preparation of PLGA nanoparticles: a factorial design study, 238 International Journal of Pharmaceutics 77-92 (2002) (“Vandervoort”). 3 Szente et al., U.S. Patent Publication No. 2005/0163853 A1, published July 28, 2005 (“Szente”). 4 Varges et al., Rheological characterization of Carbopol® dispersions in water and water/glycerol solutions, 4, 3, Fluids (2019) (“Varges”). Appeal 2021-003073 Application 14/916,439 4 Claims 44-47, 49-55, 57-59, 61-65, 67-71, 73-75, 77-81, 83, and 84 were rejected under 35 U.S.C. § 103 as obvious over the combination of Vandervoort, Labhasetwar,5 Govender,6 and Song,7 as evidence by Szente and Varges. Claims 48, 56, 66, 72, and 82 was rejected under 35 U.S.C. § 103 as obvious over the combination of Vandervoort, Labhasetwar, Govender, Song, and Chen8 as evidence by Szente and Varges. Claims 46, 47, 64, 65, and 78-85 were rejected on the ground of obviousness-type non-statutory double patenting over claims 1-5 of U.S. Patent No. 10,780,053.9 ANTICIPATION AND OBVIOUSNESS REJECTIONS The same issue is dispositive with respect each of the Examiner’s anticipation and obviousness rejections. Accordingly, we address all of the Examiner’s anticipation and obviousness rejections together. 5 Labhasetwar et al., U.S. Patent Publication No. 2009/0136585 A1, published May 28, 2009 (“Labhasetwar”). 6 Govender et al., PLGA nanoparticles prepared by nanoprecipitation: drug loading and release studies of a water soluble drug, 57 Journal of Controlled Release 171-185 (1999) (“Govender”). 7 Song et al., PLGA nanoparticles simultaneously loaded with vincristine sulfate and verapamil hydrochloride: Systemic study of particle size and drug entrapment efficiency, 350 International Journal of Pharmaceutics 320- 329 (2008) (“Song”). 8 Chen et al., WO 2005/015160 A2, published Feb. 17, 2005 (“Chen”). 9 The Examiner withdrew the provisional rejection of claims 44-59, 61-75, and 77-85 on the ground of obviousness-type non-statutory double patenting over claims 1-18 of U.S. Patent Application No. 16/619,320 in view of the terminal disclaimer filed October 13, 2020. Ans. 3. Accordingly, this rejection is no longer part of this appeal. Appeal 2021-003073 Application 14/916,439 5 The pending claims include three independent claims. Independent claim 44 requires “dissolving a pharmaceutically acceptable negatively charged agent selected from a water-soluble polymer in a first aqueous solvent to form an aqueous solution.” Independent claim 62 requires “dissolving a pharmaceutically acceptable negatively charged agent selected from a water-soluble polymer in an outer aqueous solvent to form an outer aqueous solution.” Independent claim 78 requires “dissolving a pharmaceutically acceptable polyacrylic acid and a surfactant in an outer aqueous solvent to form an outer aqueous solution.” Thus, although the language differs between claims, all three independent claims require a dissolving a polymer to form an aqueous solution. To meet this requirement, the Examiner relies Vandervoot’s disclosure of Carbopol 980 NF. Final Act.10 5 (citing Vandervoot, 79, 1:4- 5). According to the Examiner, Szente discloses that Carbopol 980 NF is a water-soluble polymer. Id. at 5-6 (citing Szente ¶¶ 81-90). In addition, the Examiner points to the definition of “solution, colloidal” in Hawley’s Condensed Chemical Dictionary, 15th ed. (2007) (“Hawley’s Dictionary”), which states: “[s]ince colloidal particles are larger than molecules it is strictly incorrect to call such dispersions solutions; however, this term is widely used in the literature.” Ans. at 5-6. Based on this definition, the Examiner argues that Appellant does not distinguish between a “true solution and a colloidal solution,” and thus “a colloidal dispersion of a polymer is a polymer solution” as claimed. Id. at 7-8. We are not persuaded. 10 Office Action mailed September 18, 2020 (“Final Act.”). Appeal 2021-003073 Application 14/916,439 6 We begin by considering the scope of the claims. As discussed above, the Examiner construes the claims such that the requirement for dissolving a polymer to form an aqueous solution can be met by using a polymer to form a colloidal dispersion. However, the Examiner does not identify, and we do not find, anything in the Specification to support such a broad claim interpretation. Moreover, this interpretation is at odds with the plain language of the claims, which requires the step of “dissolving” the claimed polymer (or, in the case of claim 78, polyacrylic acid) in an “aqueous solvent” to form an “aqueous solution.” While the Examiner has presented evidence, in the form of Hawley’s Dictionary, that the term “solution” is sometimes misused to refer to a dispersion, there is no indication that Appellant used the term “solution” in this manner in the pending claims. Indeed, given Appellant’s use of the term “dissolving,” it appears Appellant intended to exclude dispersions. Nor is there any indication in the Specification that Appellant’s use of the term “solution” encompasses dispersions. Accordingly, we construe the claims to require the claimed polymer and aqueous solvent form “[a] uniformly dispersed mixture at the molecular or ionic level, of one or more substances (the solute) in one or more other substances (the solvent).” Ans. 7 (Hawley’s Dictionary definition of “solution, true”); see also, Tr. 6 (Appellant’s counsel defining the term “water-soluble” as meaning “[t]hat the polymer forms a solution . . . [a] single phase solution”). We next consider whether the disclosure of Carbopol 980 NF in Vandervoot meets the requirements of the claims. We recognize that Szente identifies Carbopol 980 NF as a “common water-soluble ionic polymer” Szente ¶¶ 81-90. However, Appellant directs us to a wealth of evidence Appeal 2021-003073 Application 14/916,439 7 that, on its face, contradicts Szente’s teaching that Carbopol 980 NF is water-soluble. For example, Vandervoot teaches that “HPMC, poloxamer and carbopol were dispersed in distilled water at room temperature.” Vandervoot 80 (emphasis added). Thomsen11 identifies Carbopol 980 NF as a “gelling agent.” Thomsen, 6:7-16. Varges studies “[t]he influence of the solvent type on the rheological properties of Carbopol® NF 980 dispersions in water” and teaches that it was “well known that this polymer forms a colloidal dispersion when hydrated in water at controlled pH and temperature.” Varges, Abstract, 2 (emphasis added). Finally, the product specification for Carbopol 980 NF states that it forms a dispersion at a concentration of 0.5% in water. Lubrizol Product Specification.12 Considering all of the evidence together, the preponderance of the evidence supports that Carbopol 980 NF is not water-soluble. Given the bulk of the evidence supporting Carbopol 980 NF’s insolubility, we surmise that Szente missuses the term “solution” as suggested in Hawley’s Dictionary to refer to a colloidal dispersion. Because the Examiner’s anticipation and obviousness rejections rely on Carbopol 980 NF as meeting the claim requirement for a polymer that dissolves to form an aqueous solution, and because Carbopol 980 NF does not meet that requirement in light of our construction of the phrase “aqueous solution,” we reverse the Examiner’s rejections. 11 Thomsen et al., U.S. Patent No. 5,981,605, issued Nov. 9, 1999 (“Thomsen”). Thomsen was cited by Appellant as evidence that Carbopol 980 NF is not water-soluble. Appeal Br. 8. 12 The Lubrizol Product Specification is provided as Exhibit H to Appellant’s Appeal Brief. Appeal 2021-003073 Application 14/916,439 8 DOUBLE PATENTING The Examiner rejected claims 46, 47, 64, 65, and 78-85 on the ground of obviousness-type non-statutory double patenting over claims 1-5 of U.S. Patent No. 10,780,053. Appellant argues that this rejection is improper in view of the terminal disclaimer filed and approved on October 13, 2020. Reply Br. 3. The issue of whether the terminal disclaimer is proper is not a matter for the Board to decide. See MPEP § 1201 (“The line of demarcation between appealable matters for the Board and petitionable matters for the Director of the U.S. Patent and Trademark Office (Director) should be carefully observed.”). See also 35 U.S.C. § 134(a) (limiting appeal before the Board to rejected claims of a patent application). As Appellant does not challenge this rejection on the merits, we summarily affirm the Examiner’s double patenting rejection. Appeal 2021-003073 Application 14/916,439 9 CONCLUSION In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 44-47, 49-55, 57, 58, 61-65, 67-71, 73-75, 77-81, 83, 84 102 Vandervoot 44-47, 49-55, 57, 58, 61-65, 67-71, 73-75, 77-81, 83, 84 44-47, 49-55, 57-59, 61-65, 67-71, 73-75, 77-81, 83, 84 103 Vandervoot, Labhasetwar, Govender, Song 44-47, 49-55, 57-59, 61-65, 67-71, 73-75, 77-81, 83, 84 48, 56, 66, 72, 82 103 Vandervoort, Labhasetwar, Govender, Song, and Chen 48, 56, 66, 72, 82 46, 47, 64, 65, 78-85 Nonstatutory Double Patenting 46, 47, 64, 65, 78-85 Overall Outcome 46, 47, 64, 65, 78-85 44, 45, 48-59, 61-63, 66-75, 77 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-IN-PART