Ex Parte Chen et alDownload PDFPatent Trial and Appeal BoardJul 15, 201611278472 (P.T.A.B. Jul. 15, 2016) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 111278,472 31498 7590 Durect Corporation 10260 Bubb Road Cupertino, CA 95014 0410312006 07118/2016 FIRST NAMED INVENTOR GuohuaChen 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 ATTORNEY DOCKET NO. CONFIRMATION NO. DURE-312 DIV 6429 EXAMINER VU, JAKE MINH ART UNIT PAPER NUMBER 1618 MAILDATE DELIVERY MODE 07/18/2016 PAPER 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. PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte GUOHUA CHEN and DAVID PRIEBE1 Appeal2014-006773 Application 11/278,472 Technology Center 1600 Before JEFFREYN. FREDMAN, RICHARD J. SMITH, and TA WEN CHANG, Administrative Patent Judges. CHANG, Administrative Patent Judge. DECISION ON APPEAL Appellants appeal under 35 U.S.C. § 134(a) involving claims to methods of administering a beneficial agent to a subject comprising providing an injectable depot composition, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM. STATEMENT OF THE CASE According to the Specification, prior art polymer compositions for injectable implants have used solvent or plasticizers that are relatively 1 Appellants identify the Real Party in Interest as Durect Corporation. (Appeal Br. 3.) Appeal2014-006773 Application 11/278,472 soluble in aqueous body fluids. (Spec. if 8.) Further according to the Specification, when such implants are placed in the body and exposed to aqueous body fluids they take up water rapidly, which often results in an uncontrolled release of beneficial agent contained within the implant. (Id.) The Specification states that the present invention "provides controlled release of [a] beneficial agent to the subject being treated, the release being controlled over a period equal to or less than two weeks after administration, [preferably] a period of about 3 to about 7 days." (Id. if 12.) Claims 11-14, 16, 18-20, 23-33, 37, and 39 are on appeal. Claim 11 is illustrative and reproduced below with key limitations emphasized: 11. A method of administering a beneficial agent to a subject, compnsmg: providing an injectable depot composition comprising: (a) a bioerodible, biocompatible polymer having a weight average molecular weight ranging from 3 000 to 9000; (b) a solvent selected from the group consisting of aromatic alcohols, esters of aromatic acids, aromatic ketones, and mixtures thereof, said solvent having miscibility in water of less than or equal to 7% at 25°C, and present in an amount from about 95 to about 10% by weight, based on the combined weight of the polymer and the solvent; and ( c) a beneficial agent; wherein said composition remains a gel after implantation and the polymer and solvent are selected to provide a composition that is sufficient to deliver the beneficial agent in a controlled manner over a duration of less than about seven days; and administering said composition to the subject. 2 Appeal2014-006773 Application 11/278,472 The Examiner rejects claims 11-14, 16, 18-20, 23-33, 37, and 39 under 35 U.S.C. § 103(a) as being unpatentable over Brodbeck.2,3 (Ans. 2.) DISCUSSION Issue The Examiner has rejected claims 11-14, 16, 18-20, 23-33, 37, and 39 under 35 U.S.C. § 103(a) as being unpatentable over Brodbeck. The Examiner finds that Brodbeck teaches a method of administering a beneficial agent to a subject comprising . . . providing a gel composition comprising: 40-60% of a polymer, such as a PLGA, which is a copolymer of lactic acid and glycolic acid, with molecular weight of about 8,000-13,000, preferably 10,000; 50% of a solvent, such as benzyl benzoate; a beneficial agent, such as hormone; and administering said composition to the subject. (Final Act. 3 (citations omitted).) The Examiner further finds that Brodbeck teaches delivery period of less than 7 days. (Id.) The Examiner finds that Brodbeck does not "specifically teach the specific polymer weight average molecular weight range ... claimed by Applicant." (Id.) However, the Examiner finds that this limitation is obvious because "[t]he weight average molecular weight of a polymer in a composition is clearly a result effective parameter that a person of ordinary skill in the art would routinely optimize." (Id.) Appellants contend that Brodbeck does not disclose the weight average molecular weight range of its polymers and only discloses number 2 Brodbeck et al., U.S. Patent No. 6,130,200, issued Oct. 10, 2000 ("Brodbeck"). 3 Claims 36 and 38 have been cancelled. (Amendment after Final Act. 6 (July 22, 2013).) 3 Appeal2014-006773 Application 11/278,472 average molecular weights, and also contend that the Examiner does not have support for the conclusion that weight average molecular weight of the polymer is a result effective parameter that a skilled artisan would optimize. (Appeal Br. 7, 9.) Appellants additionally contend that, even if it were obvious to use a polymer having a weight average molecular weight from 3000 to 9000, it would not have been obvious to "pick and choose from the broad teachings of Brodbeck" to arrive at an embodiment having a delivery period of less than 7 days, since such an embodiment is not preferred. (Id. at 9.) Finally, Appellants contend that the claims are non-obvious because the claimed formulations "surprisingly provide a controlled, sustained release of beneficial agent over a short duration of time." (Id. at 10.) The issues with respect to this rejection are ( 1) whether Brodbeck renders obvious the limitation of a polymer having a weight average molecular weight ranging from 3000 to 9000 for use in an injectable depot composition in a method of administering a beneficial agent to a subject; (2) whether Brodbeck renders obvious an injectable depot composition having the claimed components that deliver a beneficial agent in a controlled manner over a duration of less than about seven days; and (3) whether the claimed formulations provide unexpected results that, when weighed with the evidence supporting the prima facie case, shows that the claimed formulations would not have been obvious. Findings of Fact 1. Brodbeck teaches " [ m] ethods and compositions for systematically or locally administering ... a beneficial agent to a subject." (Brodbeck Abstract.) 2. Brodbeck teaches an injectable gel composition comprising: 4 Appeal2014-006773 Application 11/278,472 A) mixing a biocompatible polymer and a solvent having a miscibility in water of 7% or less selected from lower alkyl and aralkyl esters of benzoic acid to form a viscous gel; B) dispersing or dissolving a beneficial agent, optionally associated with a solubility modulator of the beneficial agent, in an emulsifying agent to form a beneficial agent containing emulsifying agent; and C) mixing the beneficial agent containing emulsifying agent with the viscous gel, said beneficial agent containing emulsifying agent forming a dispersed droplet phase in the viscous gel, and optionally, D) mixing one or more of a pore former and an osmotic agent with said viscous gel. (Brodbeck 6: 46-61.) 3. Brodbeck teaches solvent or solvent mixture present in an amount of "from about 95 to about 20% by weight ... [,] preferably ... 70 to about 30% by weight and often 60-40% by weight of the viscous gel, i.e., the combined amounts of the polymer and the solvent." (Id. at 17:51-56.) 4. Brodbeck teaches that its gel compositions can provide controlled release of the beneficial agent. (Id. at 1: 10-12.) 5. Brodbeck defines the term "prolonged period" to mean "a period of time over which release of a beneficial agent from the implant of the invention occurs, which will generally be about one week or longer, and preferably about 30 days or longer." (Id. at 10:1--4.) 6. Brodbeck discloses poly(lactide-co-glycolide )copolymers, or PLGA, as a most preferred polymer. (Id. at 11: 17-18.) 7. Brodbeck discloses that the lactic acid-based polymer of its invention has a "number average molecular weight of from about 1,000 to about 120,000, preferably from about 5,000 to about 30,000 as determined by gas phase chromatography." (Id. at 11:23-26; see also id. at claim 15.) 5 Appeal2014-006773 Application 11/278,472 8. Brodbeck discloses an especially preferred embodiment where "the primary solvent is selected from lower alkyl and aralkyl esters of benzoic acid and the polymer is a lactic-acid based [polymer] preferably PGLA, having a number average molecular weight of between about 8,000 to about 13,000, preferably about 10,000." (Id. at 13:66-14:4.) 9. Brodbeck discloses that "[t]he low water uptake, i.e., limited water migration into the gel composition after implantation, permits the practitioner of the invention to limit beneficial agent transfer by diffusion and enhance control of the delivery profile of the beneficial agent by controlling the bioerosion characteristic of the polymer." (Id. at 14:15-20.) 10. Brodbeck discloses that "[t]he limit on the amount of beneficial agent released in the first 24 hours that is either desired or required will depend on circumstances such as the overall duration of the delivery period." (Id. at 16:58---61.) Brodbeck further discloses that, "[t]ypically, higher percentages of release in the first 24 hours can be tolerated if the duration of the delivery period is relatively short, e.g., less than 7-14 days." (Id. at 16:67-17:2.) 11. Brodbeck discloses that, "[ d]epending on the particular solvent or solvent mixture selected, the polymer and [the] beneficial agent, and optionally solubility modulators of the beneficial agent," the gel compositions of its invention may provide different release profile characteristics such as burst index. (Id. at 17:5-20.) 12. Brodbeck discloses that, "for a given polymer and solvent, by adjusting the amounts of these components and the amount of the beneficial agent, one can obtain a release profile that depends more on the degradation 6 Appeal2014-006773 Application 11/278,472 of the polymer than the diffusion of the beneficial agent from the composition or vice versa." (Id. at 21 :49-54.) 13. Brodbeck discloses that [r]elease rates and loading of beneficial agent will be adjusted to provide for therapeutically-effective delivery of the beneficial agent over the intended sustained delivery period .... While the release rate ... depends on the particular circumstances, such as the beneficial agent to be administered, release rates on the order of from about 0.1 to about 100 micrograms ... for periods of from about 7 to about 90 days can be obtained. Greater amounts may be delivered if delivery is to occur over shorter periods. (Id. at 21:66-22:11.) Analysis Claims 11-14, 16, 18-20, 23, and 25-28 We agree with the Examiner that Brodbeck renders claim 11 prima facie obvious. Brodbeck discloses a method of administering a beneficial agent to a subject. (FPL) Brodbeck teaches an injectable composition comprising a bioerodable, biocompatible polymer such as PLGA, a solvent having miscibility in water of 7% or less selected from esters of benzoic acid, and a beneficial agent. (FF2, FF6, FF9.) Brodbeck teaches solvent present in an amount from about 95 to about 20% by weight of the viscous gel (i.e., the combined amounts of the polymer and the solvent). (FF3.) Brodbeck teaches that its gel composition can provide controlled release of the beneficial agent and further discloses various delivery periods including delivery periods of less than 7-14 days. (FF5, FFlO, FF13.) While Brodbeck does not explicitly disclose the polymer having a weight average molecular weight ranging from 3000 to 9000, we find that the Examiner has 7 Appeal2014-006773 Application 11/278,472 made a reasonable showing that the molecular weight of the polymer is a result effective variable a skilled artisan would look to optimize. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456 (CCPA 1955). Appellants contend that Brodbeck does not disclose weight average molecular weight range of its polymers and only discloses number average molecular weight. (Appeal Br. 7.) Appellants contend that the number average molecular weight of a polymer is often much lower than the weight average molecular weight of the polymer; thus, Appellants argue that "even if Brodbeck discloses the use of polymers having a number average molecular weight of about 10,000, such disclosure does not render obvious the use of polymers having a weight average molecular weight ranging from 3000 to 9000." (Id.) We are not persuaded. Appellants rely on Brodbeck's disclosure that the typical polymer molecular weights in the range of 14,400-39,700 weight average molecular weight translates to 6,400-12,200 number average molecular weight. (Appeal Br. 7; Brodbeck 25:13-15.) However, Brodbeck elsewhere discloses that the lactic acid-based polymer of its invention has a number average molecular weight range between 1,000 to about 120,000. (FF7.) Even if Appellants were correct that the number average molecular weight is often much lower than the weight average molecular weight, we find that it is reasonable to conclude that the lower end of the number average molecular weight range disclosed in Brodbeck (i.e., 1,000 to 120,000) renders obvious the claimed weight average molecular weight range of 3,000 to 9,000. 8 Appeal2014-006773 Application 11/278,472 Appellants contend that the Examiner has not shown that the weight average molecular weight of the polymer is a result effective parameter. (Appeal Br. 9.) In particular, Appellants argue that, although Brodbeck generally discloses that the solvent, polymer, and beneficial agent are variables affecting the burst index of the composition, Brodbeck fails to disclose what aspects of the polymer affect burst index. A skilled artisan would understand that polymers involve many variables other than molecular weight, including monomer, comonomer, monomer ratio, end groups. Brodbeck fails to disclose controlling burst index by adjusting polymer molecular weight, let alone weight average molecular weight. (Reply at 7.) We disagree. As Appellants acknowledge, Brodbeck discloses that, "[ d]epending on the particular solvent or solvent mixture selected, the polymer and [the] beneficial agent, and optionally solubility modulators of the beneficial agent," the gel compositions of its invention may provide different release profile characteristics such as burst index. (FF 11; see also FF9.) Moreover, molecular weight is an important characteristic of a polymer, as evidenced by Brodbeck's specification of the range of molecular weights of the polymers to be used in its invention. (FF7.) We thus find that the Examiner has established by a preponderance of evidence that polymer molecular weight is a result effective variable. We note but find unpersuasive Appellants' contention that it would not have been obvious to "pick and choose from the broad teachings of Brodbeck" to arrive at an embodiment having a delivery period of less than 7 days, since such an embodiment is not preferred. (Appeal Br. 9.) Although Brodbeck defines the term "prolonged period" to mean "a period of time over which release of a beneficial agent from the implant of the 9 Appeal2014-006773 Application 11/278,472 invention occurs, which will generally be about one week or longer, and preferably about 30 days or longer" (FF5), Brodbeck clearly suggests that the release period may be shorter than 7 days and that the release rates may be adjusted accordingly. (FFlO, FF13.) Finally, Appellants contend that the claims are non-obvious because the claimed formulations "surprisingly provide a controlled, sustained release of beneficial agent over short duration of time." (Appeal Br. 10; Reply Br. 9-11.) This is not persuasive. As an initial matter, Brodbeck discloses that its compositions also provide controlled release of beneficial agents and further suggests that the release period could be shorter than seven days as claimed. (FF 4, FF 10, FF 13.) Thus, the results set forth in Appellants' Specification are not unexpected. (Ans. 5.) Moreover, to the extent Appellants argue that it is surprising that the claimed low molecular weight polymers provide controlled release over a short duration of time as compared to polymers with higher molecular weights outside of the claimed range, the data in the Specification does not show unexpected results commensurate with the scope of the claims and does not show the claimed range of molecular weights to be critical. In re Lindner, 457 F .2d 506, 508 (CCP A 1972) ("It is well established that the objective evidence of nonobviousness must be commensurate in scope with the claims."). In particular, the Specification provides comparative data for only polymers with molecular weights 7,000 and 8,000, at the higher end of the claimed range of 3,000 to 9,000. (Specification Tables 1-3.) Neither does the Specification provide any reasoning why polymers with these two molecular weights would be representative over the entire claimed range. 10 Appeal2014-006773 Application 11/278,472 Furthermore, the data in the Specification shows that formulation 7-10 contain polymers with molecular weights in the claimed range. 4 (Id. at Tables 2-3.) However, Figure 6-9 show that none of these formulations have the claimed release periods of less than seven days, while Figure 9 also show that formulations 11, containing a polymer with molecular weight outside of the claimed range, has a release profile similar to formulation 10, including an apparent release period of approximately nine days. 5 (Specification Table 2-3, Figures 6-9.) Accordingly, we find claim 11 obvious in light of Brodbeck. Claims 12-14, 16, 18-20, 23, and 25-28 have not been argued separately and therefore fall with claim 11. 37 C.F.R. § 41.37(c)(l)(iv). Claims 24, 29, 30-33, 37, and 39 Appellants rely on the same arguments as above in contending that claims 24, 29, 30-33, 37, and 39 are not obvious. (Appeal Br. 11-15.) We find these arguments unpersuasive for the same reasons set forth above. Appellants further contend that the argument for patentability for these claims is even stronger than for claim 11, because the embodiments used in the Specification to show unexpected results also fall within these narrower dependent claims. (Id.) For the reasons already discussed, we are not persuaded that Appellants have shown evidence of unexpected results that, 4 Formulation 7 contains a polymer with molecular weight of 7,000, and formulations 8-10 contain polymers with molecular weight of 8,000. (Spec. Tables 2-3.) 5 Because the last data points in the release profile data in the Specification do not show a drug plasma level of zero for any of the formulations, it is unclear whether that data point in fact represents the end of the release period as Appellants appear to contend. (Appeal Br. 10.) Nevertheless, we assume that is the case for purposes of this analysis. 11 Appeal2014-006773 Application 11/278,472 when weighed with the evidence supporting the prima facie case, show these claims to be non-obvious. We thus find these claims obvious in light of Brodbeck as well. SUMMARY For the reasons above, we affirm the Examiner's decision rejecting claims 11-14, 16, 18-20, 23-33, 37, and 39. 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 12 Copy with citationCopy as parenthetical citation