Henry Smith et al.

Patent Trials and Appeals Board

Feb 11, 2022

2021005440 (P.T.A.B. Feb. 11, 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. 16/115,973 08/29/2018 Henry J. Smith JSMIT-011G 6129 154838 7590 02/11/2022 Camran V Parast 325 Farallon Ave. Pacifica, CA 94044 EXAMINER RONEY, CELESTE A ART UNIT PAPER NUMBER 1612 NOTIFICATION DATE DELIVERY MODE 02/11/2022 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): cparast@gmail.com cparast@icloud.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte HENRY J. SMITH and JAMES R. SMITH Appeal 2021-005440 Application 16/115,973 Technology Center 1600 Before JOHN G. NEW, MICHAEL A. VALEK, and JAMIE T. WISZ, Administrative Patent Judges. WISZ, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims 14-23. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies Henry J. Smith and James R. Smith as the real parties-in-interest. Appeal Br. 3. Appeal 2021-005440 Application 16/115,973 2 CLAIMED SUBJECT MATTER The Specification describes an approach to drug development that focuses on the “proliferative capacity” of the cancer cells making up the tumor rather than on the nature of its cellular differentiation and/or cell lineage. Spec. ¶ 5. The Specification describes the “incorporation of multiple cancer drugs into a single stabilized liposome formulation in order to achieve improved efficacy and safety in treating tumors.” Id. ¶ 8. According to the Specification, “each of the component drugs selected will target a different phase of the cell-cycle of the cancer cell, thus expanding the number of cancer cells that can be killed at one time without compromising the safety of the patient.” Id. Independent claim 14, the only independent claim, is illustrative of the claimed subject matter and is reproduced below: 14. A method for forming a pharmaceutical composition for targeting tumor cells based upon their proliferative capacity and not on the cell type from which they originate, wherein the method comprises the steps of: selecting a first cytotoxic drug based upon that first cytotoxic drug selectively targeting a first phase in the cell- cycle of tumor cells; selecting a second cytotoxic drug based upon that second cytotoxic drug selectively targeting a second phase in the cell- cycle of tumor cells, the second phase in the cell-cycle of tumor cells being different from the first phase in the cell-cycle of tumor cells; and enclosing the first and second cytotoxic drugs within a liposome; wherein the first cytotoxic drug is water soluble and enclosed within an aqueous interior of the liposome; Appeal 2021-005440 Application 16/115,973 3 wherein the second cytotoxic drug is lipid soluble and incorporated into a lipid bilayer of the liposome; and wherein the incorporation of each of the first cytotoxic drug and the second cytotoxic drug within the liposome is limited to a dosage less than the known therapeutic dose of that cytotoxic drug standing alone. Appeal Br. 24 (Claims App.). REJECTION The Examiner rejected claims 14 and 17-19 under 35 U.S.C. § 103 as being unpatentable over Tardi.2 The Examiner rejected claims 15-16 and 20-22 under 35 U.S.C. § 103 as being unpatentable over Tardi in view of Allen.3 The Examiner rejected claim 23 under 35 U.S.C. § 103 as being unpatentable over Tardi, in view of Allen and further in view of Smith.4 ISSUES AND ANALYSIS Rejection of claims 14 and 17-19 under 35 U.S.C. § 103 as being unpatentable over Tardi. The Examiner finds that “Tardi teaches methods of forming pharmaceutical compositions . . . for the treatment of a neoplasm, where combinations of active agents that inhibited more than one mechanism of uncontrolled cell proliferation were chosen.” Final Act. 2 (citing Tardi ¶ 137). The Examiner finds that Tardi discloses selecting combinations of agents that effect specific points within the cell cycle resulting in non- 2 Tardi et al., US 2004/0022817 A1, published Feb. 5, 2004 (“Tardi”). 3 Allen et al., US 2004/0191307 A1, published Sept. 30, 2004 (“Allen”). 4 Smith et al., US 2009/0041837 A1, published Feb. 12, 2009 (“Smith”). Appeal 2021-005440 Application 16/115,973 4 antagonistic (e.g., synergistic) effects of the agents. Id. (citing Tardi ¶ 137). The Examiner also finds that Tardi discloses the use of active agents in combination including DNA damaging agents such as daunorubicin (an anthracycline), and S/G2 or G2/M checkpoint inhibitors, such as paclitaxel (a plant alkaloid). Id. at 3 (citing Tardi ¶ 136). According to the Examiner, Tardi also teaches that the agents are encapsulated within liposomes, whereby the encapsulation of the agent was by association with the bilayer through covalent or non-covalent interaction with the lipid components, or by entrapment within the aqueous interior of the liposome. Id. (citing Tardi ¶¶ 24, 83, 147). The Examiner further finds that Tardi teaches that synergistic interactions between two or more drugs has the benefit of lowering the amount of each drug required to result in a positive effect (i.e., dose- reduction). Id. (citing Tardi ¶¶ 2, 16, 23-28). According to the Examiner, Tardi’s dose reduction index (DRI) is a measure of how much the dose of each drug in a synergistic combination may be reduced at a given level, compared with the doses for each drug alone, which is important in clinical situations where dose-reduction leads to reduced toxicity for the host while maintaining therapeutic efficacy. Id. (citing Tardi ¶ 221). The Examiner acknowledges that Tardi does not specifically state that daunorubicin is enclosed within the aqueous interior, and paclitaxel is incorporated within the lipid bilayer but finds that Tardi teaches that encapsulation of an agent is by association with the bilayer through covalent or non-covalent interaction with the lipid components, or by entrapment within the aqueous interior of the liposome. Id. at 5. According to the Examiner, “[s]ince danorubicin is hydrophilic and paclitaxel is hydrophobic, Appeal 2021-005440 Application 16/115,973 5 one would reasonably expect the former to become incorporated into the aqueous interior of the liposome, and paclitaxel into the bilayer of the liposome.” Id. Appellant argues that Tardi does not render the method of claim 14 obvious because it teaches selecting drugs based on tumor type rather than according to their proliferative capacity. Appeal Br. 12-16. According to Appellant, Tardi teaches that it is essential that every drug disclosed in their invention be tested against a panel of tumor cell lines in vitro and that only those that show activity against at least one cell line can be included in the invention. Id. at 12-13 (citing Tardi ¶¶ 24, 26, 108-109, claims 1, 2). Based on this disclosure, Appellant concludes that Tardi teaches selecting drugs based on tumor type. Id. at 13. Appellant also contends that Tardi does not teach using a combination of drugs wherein each drug targets a different phase in the cell-cycle of the tumor cell. Id. at 17-19. According to Appellant, checkpoint inhibitors are not the same as drugs that target phases in a cell cycle and Tardi does not teach that any of the listed agents are being combined to specifically target different phases in the cell cycle. Id. at 17. Appellant also argues that Tardi does not teach the combination of daunorubicin and paclitaxel because Tardi teaches a list of agents that can be combined in many different possible combinations but does not teach any particular combination of those agents or give a reason why a particular combination would be desirable. Reply 8 (citing Tardi ¶ 136). According to Appellant, Tardi does not limit its teachings to the exemplary agents listed in paragraph 136 and because “Tardi has listed different categories of cancer drugs including ‘cytotoxic agents’ (i.e. all cancer drugs) that can be used in their invention we are sure Appeal 2021-005440 Application 16/115,973 6 that there are at least 100 cancer drugs that can be combined according to Tardi.” Id. at 8-9. Appellant concludes that “[a] simple calculation reveals that 100 cancer drugs would result in 4,950 possible two-drug combinations,” without a teaching of which combination to select. Id. at 9. Appellant further argues that Tardi does not teach that the amount of each drug in the liposomal formulation is less than the therapeutic dose of the predicate free drug. Appeal Br. 20. Appellant contends that “Tardi teaches that to arrive at a drug formulation incorporating reduced amounts of each of the combined drugs it is essential to first test each drug for activity against one or more tumor cell lines in vitro.” Id. (citing Tardi ¶¶ 24, 26, 108-109). Thus, according to Appellant, none of Tardi’s teachings can be applied and the drug combinations used in Tardi will be different than the drug combinations of the invention. Id. Last, Appellant argues that the invention meets a long-standing unmet medical need to develop improved methods of treating cancer because the “invention teaches an unconventional approach to treating tumors that may result in novel liposomal cancer drugs being developed that are superior to the cancer drugs in use today.” Appeal Br. 23. According to Appellant, “[i]t’s been more than 50 years since liposomes were first discovered and yet to date there are only a few liposomal drugs that have been commercialized and available to the public.” Id. We find that the Examiner’s position is supported by a preponderance of the evidence. Tardi teaches the preparation of compositions for the treatment of cancer by selecting combinations of two or more active agents that inhibit different mechanisms of uncontrolled cell proliferation and together have a synergistic effect, thereby reducing the dose of each drug Appeal 2021-005440 Application 16/115,973 7 required. Tardi ¶¶ 3, 4, 137, 221. Tardi also teaches the encapsulation of these agents within liposomes, wherein the encapsulation of the agent is by association with the bilayer through covalent or non-covalent interaction with the lipid components, or by entrapment within the aqueous interior of the liposome. Tardi ¶¶ 24, 83, 147. Appellant does not contest the Examiner’s finding that it would have been obvious to one of ordinary skill in the art at the time of the invention to incorporate a hydrophilic drug such as daunorubicin in the aqueous interior of the liposome, while a hydrophobic drug such as paclitaxel would become incorporated into the bilayer of the liposome. See Final Act. 5. We agree with the Examiner that the disclosure of in vitro drug screening in Tardi does not mean that it does not also teach the selection of drugs based on the proliferative capacity of the tumor cell. See Ans. 9, 13- 14. Tardi discloses selecting combinations of agents that affect specific points within the cell cycle, resulting in synergistic effects of the agents. Tardi ¶ 137. Tardi states that, “[p]referably, for the treatment of a neoplasm, combinations that inhibit more than one mechanism that leads to uncontrolled cell proliferation are chosen for use in accordance with this invention.” Id. Moreover, Tardi states that “[t]he present invention also includes selecting combinations that block multiple pathways that would otherwise result in cell proliferation.” Id. Further, Tardi discloses determining the therapeutic activity of these agents by measuring the volume, weight inhibition, growth delay, regression, and doubling time of tumors. Id. ¶¶ 182-189. Accordingly, read as a whole, Tardi teaches that agents may be selected based on a number of factors including their effect on the proliferative capacity of the tumor cells. Appeal 2021-005440 Application 16/115,973 8 We are also not persuaded by Appellant’s contention that Tardi does not teach selecting drugs that target different phases in the cell-cycle of the tumor cell. Tardi specifically refers to the use of cell cycle control inhibitors, which are defined as agents that “interfere with the progress of a cell through its normal cell cycle, the life span of a cell, from the mitosis that gives it origin to the events following mitosis that divides it into daughter cells.” Id. ¶¶ 123, 136. Tardi also discloses “selecting combinations that effect specific points within the cell cycle thereby resulting in non- antagonistic effects” and “selecting combinations that block multiple pathways that would otherwise result in cell proliferation.” Id. ¶¶ 137. A person of ordinary skill in the art at the time of the invention would have understood that agents that effect specific points within the cell cycle and that block multiple pathways would include those that target different phases of the tumor cell-cycle. Also, as referenced by the Examiner, Tardi discloses the use of daunorubicin and paclitaxel, which are specifically referenced in the Specification as agents that target different phases of the cell-cycle of tumor cells. See id. ¶ 136; Spec. ¶¶ 16, 17. We are also not persuaded by Appellant’s argument that Tardi does not teach the combination of daunorubicin and paclitaxel. First, for the reasons discussed above, we find that Tardi renders the claimed invention obvious regardless of whether it discloses the specific combination of these two drugs. Second, we find that Tardi does teach the combination of daunorubicin and paclitaxel. Paragraph 136 of Tardi lists preferred agents that may be used in combination, naming less than 30 specific drugs. Tardi ¶ 136. We do not find this list to be so long such that it would not render the combination obvious to one of ordinary skill in the art. Simply because the Appeal 2021-005440 Application 16/115,973 9 prior art “discloses a multitude of effective combinations does not render any particular [option] less obvious.” Merck & Co. v. Biocraft Labs., Inc., 874 F.2d 804, 807 (Fed. Cir. 1989). We also are not persuaded by Appellant’s contention that Tardi does not teach that the amount of each drug in the liposomal formulation is less than the therapeutic dose of the predicate free drug. Appellant appears to base this argument on the fact that Tardi discloses in vitro screening of drug candidates. See Appeal Br. 20. For the reasons discussed above, such teachings do not prevent Tardi from rendering obvious the claimed invention. Furthermore, Tardi teaches the use of a combination of drugs that have a synergistic effect for treating cancer. Tardi ¶ 4. Tardi explains that a “synergistic interaction between two or more drugs has the benefit that it can lower the amount of each drug required in order to result in a positive effect, otherwise known as ‘dose-reduction.’” Id. ¶ 221. Tardi further discloses that such does reduction leads to reduced toxicity for the host while maintaining therapeutic efficacy. Id. Finally, with regard to Appellant’s contention that the claimed invention addresses a long-felt, unmet need, Appellant’s argument consists of the conclusory statements that the “invention teaches an unconventional approach to treating tumors that may result in novel liposomal cancer drugs being developed that are superior to the cancer drugs in use today” and that “[i]t’s been more than 50 years since liposomes were first discovered and yet to date there are only a few liposomal drugs that have been commercialized and available to the public,” without any citations or evidence. Appeal Br. 23. To constitute persuasive evidence of non-obviousness, Appellant must, however, submit “actual evidence of long-felt need, as opposed to [simply] Appeal 2021-005440 Application 16/115,973 10 argument.” In re Kahn, 441 F.3d 977, 990 (Fed. Cir. 2006). We find that Appellant has not provided sufficient evidence persuasive of the existence of a long-felt, unmet need that is allegedly satisfied by the claimed invention. Based on the above, we affirm the Examiner’s rejection of claim 14 as being unpatentable over Tardi. Claims 17-19 are not argued separately apart from the independent claim, and, therefore, fall with claim 14. See 37 C.F.R. § 41.37(c)(1)(iv). Rejection of claims 15-16 and 20-22 under 35 U.S.C. § 103 as being unpatentable over Tardi in view of Allen. The Examiner’s findings with regard to Tardi are discussed above. The Examiner also finds that Allen teaches the remaining limitations of claims 15-16 and 20-22, and that it would have been obvious to combine the teachings of Tardi and Allen. See Final Act. 8-10. Appellant only makes arguments with respect to claim 14 in its briefing. See Appeal Br.; Reply 1. Thus, for the reasons discussed above, we affirm the Examiner’s rejection of these claims. Rejection of claim 23 under 35 U.S.C. § 103 as being unpatentable over Tardi, in view of Allen and further in view of Smith. The Examiner’s findings with regard to Tardi are discussed above. The Examiner also finds that Allen and Smith teach the remaining Appeal 2021-005440 Application 16/115,973 11 limitations of claim 23, and that it would have been obvious to combine the teachings of Tardi, Allen, and Smith. See Final Act. 10-11. Appellant only makes arguments with respect to claim 14 in its briefing. See Appeal Br.; Reply 1. Thus, for the reasons discussed above, we affirm the Examiner’s rejection of these claims. CONCLUSION For the reasons described herein and those already of record, we affirm the Examiner’s rejection of claims 14-23. DECISION SUMMARY In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 14, 17-19 103(a) Tardi 14, 17-19 15-16, 20-22 103(a) Tardi, Allen 15-16, 20-22 23 103(a) Tardi, Allen, Smith 23 Overall Outcome 14-23 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) (2020). AFFIRMED