Ex Parte WeberDownload PDFPatent Trial and Appeal BoardMay 14, 201813899090 (P.T.A.B. May. 14, 2018) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE 13/899,090 05/21/2013 121974 7590 05/16/2018 KACVINSKY DAISAK BLUNI PLLC America's Cup Building 50 Doaks Lane Marblehead, MA 01945 FIRST NAMED INVENTOR Jan Weber 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. 8150BSC0045 8432 EXAMINER WHEELER, THURMAN MICHAEL ART UNIT PAPER NUMBER 1619 NOTIFICATION DATE DELIVERY MODE 05/16/2018 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): bbonneville@kdbfirm.com docketing@kdbfirm.com ehysesani@kdbfirm.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte JAN WEBER Appeal2017-000258 Application 13/899,090 1 Technology Center 1600 Before DONALD E. ADAMS, RICHARD J. SMITH, and DEVON ZASTROW NEWMAN, Administrative Patent Judges. NEWMAN, Administrative Patent Judge. DECISION ON APPEAL This appeal under 35 U.S.C. § 134 involves claims to an embolic particle for use in administering therapeutic agents. The Examiner entered final rejections for obviousness. We have jurisdiction under 35 U.S.C. § 6(b ). We AFFIRM. 1 Appellant identifies Boston Scientific Scimed, Inc. as the real party in interest. Appeal Br. 2. Appeal2017-000258 Application 13/899,090 STATEMENT OF THE CASE Background Many clinical situations benefit from regulation of the vascular, lymphatic or duct systems by restricting the flow of body fluid or secretions. For example, the technique of embolization involves the introduction of particles into the circulation to occlude blood vessels, for example, so as to either arrest or prevent hemorrhaging or to cut off blood flow to a structure or organ. Temporary occlusion of blood vessels is desirable for managing various diseases and conditions. Spec. ,r 3. The Specification discloses: embolic particles ... that comprise a biodegradable polymer and a therapeutic agent, wherein the particles are configured such that, upon administration to a body lumen of a subject, the therapeutic agent is released from the time of administration up until a first point in time that ranges anywhere from about 1 week after administration to about 4 weeks after administration, at which point in time the therapeutic agent release ceases. The particles are also configured such that particles remain present in the body lumen from the first point in time at which therapeutic agent release ceases up to a second point in time that ranges anywhere from about 2 weeks to about 12 months after the first point in time, at which point the particles are completely degraded. Id. ,I 6. Claims 1-8 and 10-19 are on appeal. Appeal Br. 4. 2 Claim 1, the sole independent claim, is illustrative and reads as follows: 1. An embolic particle comprising a biodegradable polymer and a therapeutic agent, wherein the particle is configured such that, upon administration to an body lumen of a subject, the therapeutic agent is released from the time of 2 Claim 9 is cancelled and claim 20 is withdrawn. Appeal Br. 4. 2 Appeal2017-000258 Application 13/899,090 administration up until a first point in time that ranges anywhere from about 1 week after administration to about 4 weeks after administration, at which point in time the therapeutic agent release ceases, and such that the particle remains present in the body lumen from the first point in time at which therapeutic agent release ceases up to a second point in time that ranges anywhere from about 2 weeks to about 12 months after the first point in time, at which point the particle is completely degraded, wherein said polymer is an amino-acid-based poly( ester amide). Appeal Br. 12 (Claims Appendix). Appellant seeks our review of the rejection of claims 1-8 and 10-19 under pre-AIA 35 U.S.C. § I03(a) as obvious over Baty, 3 Vera, 4 and Chu. 5 DISCUSSION The Examiner finds that Baty discloses "biodegradable microparticles adapted for injection through a catheter system, such as is useful for selective embolization procedures," which can include active agents inside "such as an anesthetic which can reduce pain during an embolization procedure." Final Act. 3. 6 The Examiner finds Baty discloses that the "microparticles are fabricated from bioresorbable polymers" and "are formed through the precipitation of polymers from a base polymer solution to form aggregates which constitute the microparticle's core, e.g. base polymer core, and are in a coated or multi-layered microparticle embodiment, i.e. shell." 3 US 2005/0175709 Al, published Aug. 11, 2005 ("Baty"). 4 M. Vera et al., Microspheres from new biodegradable poly(ester amide) with different ratios of L- and D-alaninefor controlled drug delivery, 23(6): JOURNAL OF MICROENCAPSULATION, 686-97 (September 2006) ("Vera"). 5 US 2004/0063606 Al, published Apr. 1, 2004 ("Chu"). 6 Examiner's Final Action, mailed November 3, 2014 ("Final Act.). 3 Appeal2017-000258 Application 13/899,090 Id. The Examiner finds that Baty discloses the microparticles can elute (release) a bioactive agent contained inside "over a period ranging from hours to months." Id. The Examiner finds Baty teaches that the microparticles are "fully resorbed more than 30 days after the embolotherapeutic effects are achieved," ranging from "30-180 days" but that periods as short as 6 hours to 15 days are possible. Id. The Examiner finds that Baty does not disclose an amino-acid-based poly(ester amide) as the polymer. Id. at 4. However, the Examiner finds that Vera "teaches biodegradable poly ( ester amide )s composed of sebacic acid ... for applications in drug delivery systems [and] using these polymers for a sustained release delivery system for therapeutic agents," and also discloses a synthesis scheme for the polymers. Id. The Examiner finds Vera discloses that classic polymers such as PLA and PLGA "undergo bulk degradation, creating an acidic core, which can damage pH sensitive drugs such as peptides and proteins" and that, when using these polymers, it is difficult "to obtain a continuous release during a long period, due to the polymer bulk-degradation mechanism." Id. The Examiner finds Vera discloses that the "degradation rates of the[] ( ester amide )s ... are slower than those of the classical polyesters" and that their use may "overcome some important limitations of the most commonly used biodegradable polymers. Id. at 5. The Examiner finds that Vera discloses that "better control of drug release could be achieved by delaying the degradation process such that the risk of drug damage could be reduced." Id. 4 Appeal2017-000258 Application 13/899,090 The Examiner finds that Chu discloses "polymers based on a-amino acids that provide advantageous physical, chemical and biodegradation properties [such as] suitable biodegradation (weight loss percent) properties under varying conditions." Id. The Examiner finds Chu discloses that the polymers can be catalyzed by hydrolases and used as carriers for "various drugs and other bioactive substances." Id. The Examiner finds that Chu discloses "the enzyme catalyzed biodegradation rates of the polymer can be changed by varying the polymer composition and/or the nature of the functional groups" and discloses the claimed polymeric structures. Id. at 5- 6. The Examiner concludes that the skilled artisan would have found it obvious "to provide a microparticle wherein the polymers derived from the PLGA family as taught by Baty were substituted with a polymer characterized as an amino-acid-based poly( ester amide) as taught by Vera and/or Chu." Id. at 6. The Examiner further concludes the artisan would have been motivated to make the substitution "to provide a microparticle for drug delivery in view of the many advantages associated with amino-acid- based poly(ester amide)s" taught by Chu. Id. The issue with respect to this rejection is: Does the evidence of record support the Examiner's conclusion that Baty, Vera, and Chu suggest the claimed particle? We select claim 1 as representative of the claims subject to this ground of rejection. 37 C.F.R. § 4I.37(c)(l)(iv). Findings of Fact FFI. The Specification discloses: The particles are configured such that, upon administration to a body lumen ( e.g., a blood vessel such as an artery, lymphatic 5 Appeal2017-000258 Application 13/899,090 vessel, etc.) of a subject, the therapeutic agent is released from the point of administration up until a first point in time that ranges anywhere from about 1 week after administration to about 4 weeks after administration, at which point in time the therapeutic agent release ceases. For example, the first point in time where the therapeutic agent release ceases may range anywhere from 1 week to 2 weeks to 3 weeks up to 4 weeks after administration. Spec. ,r 19. FF2. The Specification discloses that "[a]s defined herein, the point in time where therapeutic agent ceases is the point where the release rate from the particle(s) drops to below about 5 % of the maximum rate of release." Spec. ,r 21. FF3. The Specification discloses that "[a]s defined herein, the point of complete degradation [is] the point where at least 95 wt% degradation of the particle(s) has occurred relative to [the] initial weight of the particle(s) (i.e., the weight at the point of injection)." Spec. ,r 22. FF4. Baty discloses: Biodegradable, compression resistant microparticles adapted for injection through a catheter system, such as is useful for selective embolization procedures. The microparticles can optimally be neutrally buoyant relative to a target bodily fluid. Various active agents may be included in the microparticles, such [as] an anesthetic which can reduce pain during an embolization procedure. Baty, Abstract. FF5. Baty discloses that the microparticles "can be fabricated from bioresorbable polymers (which term is intended to include polymers that are 'resorbable,' capable of 'resorption,' 'bioabsorbable,' 'absorbable,' or capable of 'absorption')." Baty ,r 86. FF6. Baty discloses: 6 Appeal2017-000258 Application 13/899,090 The term "elution" is used herein to refer to any release of material from a microparticle. Materials typically provided for release include, but are not limited to bioactive agents, e.g., additives, coating materials, base polymer( s) or other material carried in, on, and/or with the microparticles. In usage, it may be stated in some embodiments that bioactive agents are "eluted" from a microsphere. "Elution Rate" is one measure of the release or removal of any substance from a microsphere over time. Elutants from a microsphere can have elution rates which are constant or which vary over time and/or under changing conditions. Baty i173. FF7. Baty discloses: microparticles can be formed through the precipitation of polymers from a base polymer solution to form aggregates which constitute a microparticle, or the microparticle' s core, are in a coated or multi-layered microparticle embodiment (also referred to as "microparticle core," "base polymer core," "core"). A base polymer solution contains one or more base polymers dissolved in an organic solvent (such as, dichloromethane, chloroform, acetone, methylene chloride, ethyl acetate, etc.). These polymers are referred to as "base polymer(s)" or "microparticle base polymer(s)." Baty i187. FF8. Baty discloses that the microparticles "can be engineered to release a substance at a controlled rate" and to "incorporate or carry one or more bioactive agents that can be locally released from the microparticle." Baty ,r 167. Further, the "drug-release can be sustained or can vary over time." Id. "Microparticles are capable of the sustained elution of a bioactive agent over a period ranging from hours to months." Id. ,r 184. Further, "[t]here are multiple methods of drug formulation with the base polymers for 7 Appeal2017-000258 Application 13/899,090 sustained controlled release for 1 to more than 45 days of one or more pharmaceutical agents." Id. ,r 239. FF9. Baty discloses that microparticles have a "'resorption profile,' or 'degradation profile'. After injection into a patient, as time progresses, hydrolytic and/or enzymatic degradation or decomposition occur. Typically, no physiologically significant amount of a given microparticle remains after a period of time (typically greater than 30 days). After 270 days complete resorption of microparticles is typical." Baty ,r 192. The microparticles "in some embodiments are fully resorbed more than 30 days after the embolotherapeutic effects are achieved [which] is complete ... from 30-180 days. Shorter time periods for resorption on the order of hours to days can be employed (e.g., 6 hrs, 12 hrs, 1 day, or 15 days)." Id. ,r 194. FFlO. Vera discloses "[a] series ofbiodegradable poly (ester amide)s composed of sebacic acid, dodecanediol and different ratios of the stereoisomers of L- and D-alanine were synthesized for applications in drug delivery systems." Vera Abstract. FF 11. Vera discloses: While the development of copolymers of lactide and glycolide (PLGA family) is among the most important advances in medical biomaterials, there are some limitations that significantly curtail their use. Concerning the degradation process, it has been found that PLA and PLGA devices undergo bulk degradation, creating an acidic core, which can damage pH sensitive drugs such as peptides and proteins .... Another limitation is the difficulty to obtain a continuous release during a long period, due to the polymer bulk-degradation mechanism. Vera 687. FF12. Vera discloses: 8 Appeal2017-000258 Application 13/899,090 In biomedical applications, requirements are always specific (no toxicity, biocompatibility, degradability) and degradation rates of these poly(ester amide)s are slower than those of the classical polyesters. Furthermore, degradation can be controlled by the ratio of the natural L-alanine isomer and it is possible to overcome some important limitations of the most commonly used biodegradable polymers. Thus, a better control of drug release could be achieved by delaying the degradation process. In the same way, the risk of drug damage could be reduced. Vera 688. FF 13. Chu discloses "elastomeric copolyester amides, elastomeric copolyester urethanes, and methods for making the same. The polymers that are based on a-amino acids and possess suitable physical, chemical and biodegradation properties. The polymers are useful as carriers of drugs or other bioactive substances." Chu Abstract. FF14. Chu discloses: The present invention provides polymers that are based on a-amino acids. In contrast to conventional poly( a-amino acids), the polymers of the present invention (e.g., elastomeric functional copolyester amides and copolyester urethanes) possess advantageous physical, chemical and biodegradation properties. For example, the polymers of the present invention possess suitable biodegradation (weight loss percent) properties under varying conditions, (see, Table III). The hydrolysis of the polymers can be catalyzed by hydro lases ( e.g., trypsin, a- chymotrypsin, lipase, etc.). As such, the polymers can be used as carriers for covalent immobilization (attachment) of various drugs and other bioactive substances. In addition, the enzyme catalyzed bi ode gradation rates of the polymer of the present invention can be changed by varying the polymer composition (e.g., 1/p ratio) and/or the nature of the functional groups (e.g., dicarboxylic acids, dials, or a-amino acids). Chu ,r 7. 9 Appeal2017-000258 Application 13/899,090 Principles of Law An invention is not patentable under 35 U.S.C. § 103 if it is obvious. KSR Int'! Co. v. Teleflex Inc., 550 U.S. 398,427 (2007). Under§ 103: the scope and content of the prior art are to be determined; differences between the prior art and the claims at issue are to be ascertained; and the level of ordinary skill in the pertinent art resolved. Against this background, the obviousness or nonobviousness of the subject matter is determined. Graham v. John Deere Co., 383 U.S. 1, 17 (1966). A central question in analyzing obviousness is "whether the improvement is more than the predictable use of prior art elements according to their established functions." KSR, 550 U.S. 417. "[W]hen a patent claims a structure already known in the prior art that is altered by the mere substitution of one element for another known in the field, the combination must do more than yield a predictable result." Id. at 416, citing United States v. Adams, 383 U.S. 39, 50-51 (1966). Analysis We adopt the Examiner's findings of fact and reasoning regarding the scope and content of Baty, Vera, and Chu and the reasons to combine the references to make the claimed microparticles (Final Act. 3---6; Ans. 3-8; FF4-FF14), and agree with the Examiner that claim 1 is rendered obvious by the combination of Baty, Vera, and Chu. We address Appellant's arguments below. Appellant argues that the rejection should be reversed because the skilled artisan would not have been motivated by the cited art "to construct an embolic particle that releases a therapeutic agent to a body lumen of a patient for an administration time of about 1 week to about 4 weeks, and 10 Appeal2017-000258 Application 13/899,090 then remains present within the patient for a period after release ceases for between about 2 weeks to about 12 months." Appeal Br. 8. According to Appellant, Baty does not disclose or suggest the release of a therapeutic agent from an embolic particle from the time of administration up until a first point in time of about 1 week and about 4 weeks, and then remain for a second period of time after release of the therapeutic agent ceases of between about 2 weeks to about 12 months. Id. Appellant argues the cited portions of Baty does not "disclose microparticles that remain present in vivo for a period of about 2 weeks to about 12 months after release of the therapeutic agent ceases." Id. We are not persuaded. Although the Examiner cited paragraph 184 in the rejection (Final Act. 3), the language cited by the Examiner plainly quotes paragraph 183. 7 In addition, "[i]t is well settled that a prior art reference is relevant for all that it teaches to those of ordinary skill in the art." In re Fritch, 972 F.2d 1260, 1264 (Fed. Cir. 1992). Baty discloses microparticles made from bioresorbable polymers that can elute drugs over time, including from as short as 6 hours to 45 days. FF4-FF8. The shell of the particle remains present until it is resorbed, which may be complete from 30-180 days. FF9--FF10. As stated by the Examiner, "the claimed range of release of a therapeutic agent from the time of administration up until a first point in time of about 1 week and about 4 weeks is encompassed by the sustained elution of a therapeutic agent over the release time period as taught by Baty." Ans. 4. Further, Baty's teachings regarding resorption of the 7 The Examiner corrects the citation at Answer 4. 11 Appeal2017-000258 Application 13/899,090 microparticles "would overlap with the claimed range of remaining for a second period of time after release of the therapeutic agent ceases of between about 2 weeks to about 12 months." Id. Where the claimed ranges overlap with the disclosures of prior art, the claim is obvious. In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003) ("In cases involving overlapping ranges, we and our predecessor court have consistently held that even a slight overlap in range establishes a prima facie case of obviousness."). Appellant further argues that none of the individual references teaches the claimed invention. In advancing that argument, Appellant discusses the individual distinctions of Baty, Vera, and Chu, but does not persuasively address the combination of their respective teachings. See, e.g., Appeal Br. 8-9. This is not persuasive as one cannot show nonobviousness by attacking references individually where the Examiner bases the rejection on a combination of references. See In re Keller, 642 F.2d 413, 425--426 (CCPA 1981 (citing cases). Appellant argues Baty "does not disclose or suggest that the microparticles cease to release the therapeutic agent at the time that embolotherapeutic effects are achieved." Appeal Br. 8-9; Reply Br. 9. Appellant argues that the cited portion of Baty "cannot be interpreted as stating that microparticles remain for a period of time after release of the therapeutic agent ceases ( e.g., as opposed to the release of the therapeutic agent ceasing at the time of full resorption)." Reply Br. 9, 13. We are not persuaded. The Specification teaches that "[a]s defined herein, the point in time where therapeutic agent ceases is the point where the release rate from the particle(s) drops to below about 5% of the 12 Appeal2017-000258 Application 13/899,090 maximum rate of release." FF2. Baty discloses that resorption of the microparticles may occur more than 30 days "after the embolotherapeutic effects are achieved [which] is complete ... from 30-180 days." FF9. Appellant does not persuasively explain why absorption occurring "after the embolotherapeutic effects are achieved" is not absorption after cessation of the drug release, as disclosed by the Specification (see FF1-FF3). Appellant next argues that the skilled artisan would not have been motivated to make the proposed substitution of Vera's amino-acid-based poly( ester amide )s in the microparticles of Baty. Appeal Br. 9; Reply Br. 10. In particular, Appellant argues that "rates for the degradation of amino- acid-based poly( ester amide) polymers differ substantially from classical polyesters (e.g., poly[ a-hydroxy esters], including homopolymers (PLA, PGA) and copolymers of lactide and glycolide (PLGA family), such as are taught in Baty," and that because of this, "the amino-acid based poly( ester amide )s would necessarily not have the release and degradation profiles claimed in claim 1" and the artisan would have had "little to no expectation" of achieving the release and degradation profiles of Baty using these polymers. Reply 14--15. However, Appellant advances no reasoning or evidence why the substitution would not work or why the release and degradation profiles would differ from those of claim 1, as suggested by the time ranges set forth in the cited art (FF8-FF9). Appellant's argument is not persuasive. [W]here the Patent Office has reason to believe that a functional limitation asserted to be critical for establishing novelty in the claimed subject matter may, in fact, be an inherent characteristic of the prior art, it possesses the authority to 13 Appeal2017-000258 Application 13/899,090 require the applicant to prove that the subject matter shown to be in the prior art does not possess the characteristic relied on. In re Schreiber, 128 F.3d 1473, 1478 (Fed. Cir. 1997); In re Best, 562 F.2d 1252, 1254--55 (CCPA 1977). The Examiner provides sound fact-based reasoning for combining the amides of Vera into the microparticles of Baty, namely, that by doing so, the degradation disadvantages of prior polymers and obtain a continuous therapeutic release during a long period. Final Act. 4. Appellant has not provided evidence or persuaded us that the combined teachings of the cited references fail to provide a reasonable expectation of success in substituting the amides to achieve the microparticles recited in claim 1. An argument made by counsel in a brief does not substitute for evidence lacking in the record. Estee Lauder, Inc. v. L 'Orea!, S.A., 129 F.3d 588, 595 (Fed. Cir. 1997). Appellant next argues that even if the amide disclosed by Vera were incorporated into the microparticle of Baty, that the ordinary artisan would not "find any motivation to design such particles to release a therapeutic agent over a period or about 1 week to about 4 weeks, and then have the particles remain for a period of about 2 weeks to about 12 months after release of the therapeutic agent ceases." Appeal Br. 9; Reply Br. 10. In response, the Examiner states: Vera teaches that the degradation rates for amino-acid-based poly( ester amide) polymers are slower than those of the classical polyesters and the degradation can be controlled by the ratio of the natural L-alanine isomer. Therefore, a better control of drug release is achieved by delaying the degradation process such that the risk of drug damage can be reduced. Ans. 6. 14 Appeal2017-000258 Application 13/899,090 In reply, Appellant argues that the skilled artisan would not be motivated to make the substitution "because Vera indicates that the rates of degradation of amino-acid-based poly( ester amide) polymers differ substantially from classical polyesters ( e.g., poly[ a-hydroxy esters] such as PLA, PGA, PLGA, etc. taught in Baty)." Reply Br. 11. We are not persuaded as it is obvious to those skilled in the art to substitute one known equivalent for another. See In re Omeprazole Patent Litigation, 483 F.3d 1364, 1374 (Fed. Cir. 2007) ("[T]his court finds no ... error in [the] conclusion that it would have been obvious to one skilled in the art to substitute one ARC [alkaline reactive compound] for another."). Appellant does not persuasively explain or provide evidence demonstration why the amides are not equivalent, why a skilled artisan would not have found it obvious to substitute the polymers of Chu and Vera for those used in the microparticle of Baty, or why such a combination would be inoperable. Appellant next repeats the arguments made with respect to Vera in reference to Chu, again without persuasive reasoning or evidence in support, and further adds that Chu and Vera lack a teaching or suggestion "that polymers based on a-amino acids would be suitable as a substitute for the classical polyesters." See Appeal Br. 13; Reply Br. 10. For the reasons discussed above, we are not persuaded. In addition, and as the Examiner noted, Chu discloses additional polymers that are based on a-amino acids and possess suitable physical, chemical and biodegradation properties, and teaches that the rate of biodegradation can be changed by varying the polymer composition (FF14) and Vera discloses potentially better control of drug release could be achieved with the disclosed polymers (FF12). Absent 15 Appeal2017-000258 Application 13/899,090 persuasive argument or evidence why the substitution would not work as achieved, we are not persuaded. Estee Lauder, 129 F.3d at 595. Rather, we agree with the Examiner that the ordinarily skilled artisan would have found the disclosed advantages as reasons to incorporate the polymers of Chu and Vera into the microparticles of Baty as proposed by the Examiner. Conclusion of Law We affirm the rejection of claim 1. Claims 2-8 and 10-19 have not been argued separately and therefore fall with claim 1. 3 7 C.F .R. § 4I.37(c)(l)(iv). SUMMARY We affirm the rejection of claims 1-8 and 10-19 under pre-AIA 3 5 U.S.C. § 103(a) as obvious over Baty, Vera, and Chu. 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 16 Copy with citationCopy as parenthetical citation