Ex Parte Teifel et alDownload PDFPatent Trial and Appeal BoardMay 25, 201710575779 (P.T.A.B. May. 25, 2017) 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. 10/575,779 09/28/2007 Michael Teifel S219-0006US 9429 29150 7590 05/30/2017 LEE & HAYES, PLLC 601 W. RIVERSIDE AVENUE SUITE 1400 SPOKANE, WA 99201 EXAMINER SCHULTZ, JAMES ART UNIT PAPER NUMBER 1633 NOTIFICATION DATE DELIVERY MODE 05/30/2017 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): lhpto@leehayes.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte MICHAEL TEIFEL, UWE MICHAELIS, BIRGITTA SAUER, KERSTIN BARTELHEIM, CHRISTOPH BRUNNER, and KURTNAUJOKS1 Appeal 2016-006546 Application 10/575,779 Technology Center 1600 Before ERIC B. GRIMES, TAWEN CHANG, and TIMOTHY G. MAJORS, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35U.S.C. § 134 involving claims to a method of treatment, which have been rejected as anticipated or obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm. 1 Appellants identify the Real Party in Interest as SynCore Biotechnology Co., Ltd. (Communication filed May 26, 2016.) Appeal 2016-006546 Application 10/575,779 STATEMENT OF THE CASE The Specification states that “administration of a cationic [positively charged] liposomal preparation having a high content of paclitaxel as an active ingredient selectively affects angiogenic endothelial cells in a human patient in need thereof.” (Spec. 5:11—14.) “The present pharmaceutical composition can be administered at a monthly dose of about 0.25 mg up to about 100 mg.” {Id. at 6:16—17.) “The monthly dose is preferably administered in a plurality of single dose units.” {Id. at 7:26—27.) Claims 36, 44—51, 64—69, 72, 73, and 85—90 are on appeal. Claim 36 is illustrative and reads as follows: Claim 36: A method of treating a human patient suffering from a disease or condition, comprising administering to a patient in need thereof a pharmaceutical composition comprising a cationic liposomal preparation comprising at least one cationic lipid from about 30 mole% to about 99.9 mole%, paclitaxel in an amount of at least about 0.1 mole%, and a neutral and/or anionic lipid from about 0 mole% to about 70 mole%, wherein the amount of paclitaxel in a single dose of the pharmaceutical composition is between 0.275 and 1.1 mg/kg body weight of the patient. The claims stand rejected as follows: Claims 36, 44, 45, 49-51, 67, 72, 73, and 85-87 under 35 U.S.C. § 102(b) as anticipated by Rahman2 (Ans. 2) and Claims 36, 44—51, 64—69, 72, 73, and 85—90 under 35 U.S.C. § 103(a) as obvious based on Rahman and McDonald3 (Ans. 5). 2 Rahman, US 6,146,659, issued Nov. 14, 2000. 3 McDonald et al., US 7,112,338 B2, issued Sept. 26, 2006. 2 Appeal 2016-006546 Application 10/575,779 I The Examiner has rejected claims 36, 44, 45, 49-51, 67, 72, 73, and 85—87 as anticipated by Rahman. The Examiner finds that “Rahman teaches administering cationic liposome-encapsulated paclitaxel.” (Ans. 4.) The Examiner also finds that Rahman teaches administering liposomal paclitaxel at a dosage of 0.5—5.0 mg/kg body weight. (Id.) The Examiner finds that Rahman therefore anticipates the claimed method. Appellants argue that the only specific cationic liposomes described by Rahman are made up of phosphatidyl choline, cholesterol, and stearyl amine, which includes a positively charged amine but no cationic lipid, as required by the claims. (Appeal Br. 7.) Appellants also argue that Rahman does not disclose administering a composition comprising paclitaxel in cationic lipids to a human patient. (Id.) We agree with Appellants that Rahman’s disclosure does not meet the standard required by 35 U.S.C. § 102(b). Rahman discloses administering liposomally encapsulated taxanes, such as paclitaxel, to a patient. (Rahman 1:10—12, 2:41—45.) Rahman discloses that “the liposomes may be neutral, negative or positive liposomes. For example, positive liposomes may be formed from a solution containing phosphatidyl choline, cholesterol, and stearyl amine.” (Id. at 3:43—46.) Rahman states that its pharmaceutical composition is administered in the amount of about 50 to 300 mg active compound/m2 of mammalian host surface area. For a human, for example, of about 70 kg body weight, from about 0.5 to 5.0 mg active compound per kg of body weight is administered. Preferably, about 1.0-3.0 mg of active compound per kg of body weight is administered. (Id. at 4:6-12.) 3 Appeal 2016-006546 Application 10/575,779 Claim 36, however, requires administering a composition comprising a liposomal preparation comprising a cationic lipid; Rahman only describes positive liposomes comprising a cationic amine (stearyl amine), not a cationic lipid, let alone a cationic lipid in a mole% of 30-99.9%, as required by claim 36. In addition, Rahman does not disclose administering any composition comprising paclitaxel encapsulated in cationic liposomes to a human patient. We therefore agree with Appellants that Rahman does not disclose all of the limitations of the rejected claims. The rejection under 35 U.S.C. § 102(b) is reversed. II The Examiner has rejected all of the claims on appeal as obvious based on Rahman and McDonald. The Examiner finds that McDonald discloses “the use of liposomally-delivered paclitaxel for the purpose of treating various cancers.” (Ans. 6.) The Examiner also finds that McDonald discloses the combination of the cationic lipid DOTAP, neutral lipid DOPC, and paclitaxel at a ratio of 50:47:3, as recited in dependent claim 48 of the instant application. (Id. at 6—7.) Finally, the Examiner finds that McDonald teaches that an appropriate dose of cationic liposomally encapsulated paclitaxel can be readily determined by a skilled artisan by starting with a small dose and increasing it until the desired results are shown. (Id. at 7.) The Examiner concludes that the claimed method would have been obvious because Rahman discloses a range of dosages that overlaps the claimed 4 Appeal 2016-006546 Application 10/575,779 range and McDonald teaches that cationic liposomes target tumors. (Id. at 7-8.) We agree with the Examiner that the method of claim 36 would have been obvious to a person of ordinary skill in the art based on Rahman and McDonald. McDonald discloses “cationic liposome delivery of taxanes to blood vessels” to inhibit angiogenesis. (McDonald 1:17—18, 6:14—25.) “‘Taxanes’ include paclitaxel.” (Id. at 20:28.) McDonald states that cationic lipids useful in its composition include “l,2-diacyl-3-trimethylammonium-propanes, (including but not limited to, dioleoyl (DOTAP),. . .).” (Id. at 17:66 to 18:3.) McDonald also states that “[njeutral lipid can be incorporated into the cationic liposome formulations, . . . including, but not limited to, a phosphatidyl ethanolamine, including, but not limited to . . . DOPC.” (Id. at 22:25—33.) McDonald discloses that one embodiment of its composition “comprises DOTAP:DOPC:paclitaxel in a 50:47:3 molar ratio.” (Id. at 22:51—52.) Thus, McDonald discloses a specific embodiment of its composition that includes each of the components recited in claim 36, in amounts that are encompassed by the claim. McDonald also discloses that cationic liposomes selectively associate with angiogenic endothelial cells and thus are useful for delivering an active agent to treat such cells. (Id. at 6:14—25.) Similarly, Rahman discloses that liposomally encapsulated paclitaxel is useful for treating patients. (Rahman 4:42-43, 4:49-50.) Therefore, it would have been obvious to use McDonald’s composition comprising a 50:47:3 molar ratio of DOTAP:DOPC:paclitaxel to treat a human patient suffering from a disease or condition, as recited in claim 36. 5 Appeal 2016-006546 Application 10/575,779 McDonald also discloses that “those skilled in the art can, using the present disclosure, readily determine appropriate dosing by first administering extremely small amounts and incrementally increasing the dose until the desired results are obtained.” (McDonald 24:38-42.) In addition, Rahman suggests that, “[f]or a human, for example, of about 70 kg body weight, from about 0.5 to 5.0 mg active compound per kg of body weight is administered. Preferably, about 1.0-3.0 mg of active compound per kg of body weight is administered.” (Rahman 4:8—12.) Based on these disclosures, it would have been obvious to a skilled artisan to select a dosage at the lower end of Rahman’s dosage ranges—such as 0.5 or 1.0 mg/kg body weight—as the starting point for the dosage optimization suggested by McDonald. The prior art provides a reason to do so, because McDonald suggests beginning the optimization process “by first administering extremely small amounts and incrementally increasing the dose until the desired results are obtained.” (McDonald 24:38-42.) Therefore, it would have been obvious to use the smallest amount suggested in the references, Rahman’s 0.5 mg/kg body weight, as the starting dosage for McDonald’s dosage optimization. Appellants argue that “Rahman only discloses delivery of therapeutic agents using anionic [negatively charged] liposomes” and “[t]he dose of paclitaxel for delivery to a human patient using the anionic liposomes of Rahman is not applicable to the delivery of paclitaxel using cationic liposomes.” (Appeal Br. 9.) Appellants cite the Lander Declaration4 as 4 Declaration under 37 C.F.R. § 1.132 of Thomas Lander, filed July 3, 2013. 6 Appeal 2016-006546 Application 10/575,779 evidence that cationic liposomes are structurally and functionally different from anionic liposomes. {Id. at 9—10.) This argument is unpersuasive, because Rahman states that its method can be practiced with neutral, negatively charged, or positively charged liposomes, and does not make any distinction in its recommended dosages based on the type of liposomes used. (Rahman 3:43—44, 4:6—13.) Thus, regardless of structural or functional differences, a skilled worker would have reasonably expected the dosage ranges disclosed by Rahman to be useful for compositions with neutral, negatively charged, or positively charged liposomes. In addition, McDonald provides reason to use cationic lipids to deliver paclitaxel and suggests optimizing dosages by starting with extremely small amounts and incrementally increasing the dosage. We agree with the Examiner that the claimed method would have been obvious based on the combined disclosures of the references. Appellants cite the Lander Declaration as evidence that “clinicians would not have used cationic liposomal formulations containing low doses of paclitaxel.” (Appeal Br. 10.) Dr. Lander declared that the conventional method of treating patients with paclitaxel was to administer up to the maximum tolerated dose (MTD) of paclitaxel in an attempt to eradicate all tumor cells as quickly and completely as possible. However, the conventional method of administering MTD of paclitaxel caused severe side effects because a large dose of paclitaxel was administered to the patient. (Lander Deck 14(a)(ii).) Dr. Lander does not, however, cite any evidence showing the “conventional” nature of the described treatment, and it is contrary to the express disclosure of McDonald that those skilled in the art determine 7 Appeal 2016-006546 Application 10/575,779 appropriate dosing by starting with small amounts and gradually increasing the dosage. (McDonald 24:38-42.) McDonald also discloses that its method “makes it possible to administer substantially smaller amounts of any substance as compared with delivery systems which target the surrounding tissue.” {Id. at 24:44-47.) Thus, we find that the cited references would not have suggested starting with a high dose that was likely to cause severe side effects. Appellants also argue that the dosages disclosed in Rahman that are in units of mg/m2 (milligrams per square meter of body surface area) do not overlap the range in claim 36. (Appeal Br. 11—12.) Appellants argue that when Rahman’s mg/m2 dosage ranges are converted to mg/kg using the conversion factor described by Freireich,5 they result in dosages that are outside of the claimed range. {Id. at 12—13.) Appellants cite Ex parte Darr, Appeal No. 2011-0011436 (PTAB 2013), as supporting their position that when the units used in a reference are obviously incorrect, a rejection based on use of those units should be reversed. (Appeal Br. 14.) These arguments are unpersuasive. Regarding Appellants’ argument based on converting the dosage ranges in Rahman from mg/kg to mg/m2 and vice versa, we agree with the Examiner (Ans. 17) that no conversion would be necessary for a skilled worker to understand Rahman’s dosages that are expressed in mg/kg, because they are expressly set forth in those units. 5 Freireich et al., “Quantitative Comparison of Toxicity of Anticancer Agents in Mouse, Rat, Hamster, Dog, Monkey, and Man,” 50 Cancer Chemother. Rep. 219—244 (1966). 8 Appeal 2016-006546 Application 10/575,779 Appellants’ argument regarding Ex parte Darr is also unpersuasive. That decision dealt with an appeal in which the evidence showed that “one of ordinary skill in the art would immediately recognize 0.827 as inches rather than millimeters as the unit of length for distance ‘e.’” Darr, slip opinion at 4. Here, by contrast, the evidence does not show that a person of ordinary skill in the art would immediately recognize Rahman’s disclosure of certain dosage ranges in units of mg/kg to be typographical errors, or indeed to have anything other than their plain meaning. Finally, Appellants argue that the Examiner has not adequately responded to the Lander Declaration. (Appeal Br. 15.) Appellants then address the references cited by the Examiner in responding to the Lander Declaration {id. at 15—17) and conclude that “[t]he Examiner has improperly dismissed the declaration of Dr. Lander as providing mere opinion” {id. at 17). This argument is also unpersuasive. We have thoroughly considered the Lander Declaration but find that it does not provide evidence that outweighs the evidence of obviousness provided by Rahman and McDonald. Dr. Lander cites three references as describing clinical trials using liposome- encapsulated paclitaxel at doses higher than those recited in claim 36. (Lander Deck 14(a)(iii).) Dr. Lander declares that “low dosages of paclitaxel, such as those recited in the claims of U.S. Application ’779, were not used clinically for treatment purposes.” {Id. 14(a)(iv).) This evidence is not persuasive of nonobviousness, because McDonald suggests using extremely small dosages as the starting point for dosage optimization (McDonald 24:38-42); states that cationic liposomes 9 Appeal 2016-006546 Application 10/575,779 selectively associate with angiogenic endothelial cells (id. at 6:14—25.); and discloses that using cationic liposomes to deliver paclitaxel allows substantially smaller amounts to be used (id. at 24:44-45.) Dr. Lander does not describe any of the cited clinical trials as using paclitaxel encapsulated in cationic liposomes. Dr. Lander also states that “[cjationic liposomes are structurally and functionally different from neutral and anionic liposomes for delivery of agents.” (Lander Decl. 14(b).) This point has been addressed above. To reiterate, Rahman would have led a skilled artisan to expect that the same range of dosages of liposomally encapsulated paclitaxel would be effective regardless of the type of liposome, and McDonald suggests using small amounts of paclitaxel in cationic liposomes for dose optimization, and suggests that they preferentially target angiogenic epithelial cells, enabling effective dosages with smaller amounts of paclitaxel. Finally, Dr. Lander discusses the teachings of McDonald and Rahman individually. (Lander Decl. 14(c), (d).) Dr. Lander concludes that “[a] clinician would not have combined the teachings of McDonald and Rahman and would not have applied the teachings of one reference to the other as they are directed to delivery of active agents using structurally and functionally different liposomes.” (Id. 14(e).) For the reasons thoroughly discussed above, however, we conclude that a preponderance of the evidence of record supports the Examiner’s conclusion that the method of claim 36 would have been obvious to a person of ordinary skill in the art based on Rahman and McDonald. 10 Appeal 2016-006546 Application 10/575,779 Claims 44—51, 64—69, 72, 73, and 85—90 have not been argued separately and therefore fall with claim 36. 37 C.F.R. § 41.37(c)(l)(iv). SUMMARY We reverse the rejection of claims 36, 44, 45, 49-51, 67, 72, 73, and 85—87 under 35 U.S.C. § 102(b) as anticipated by Rahman. We affirm the rejection of claims 36, 44—51, 64—69, 72, 73, and 85—90 under 35 U.S.C. § 103(a) based on Rahman and McDonald. 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 11 Copy with citationCopy as parenthetical citation