Sengun, Mehmet Z. et al.Download PDFPatent Trials and Appeals BoardApr 21, 202013250086 - (D) (P.T.A.B. Apr. 21, 2020) 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. 13/250,086 09/30/2011 Mehmet Z. Sengun 47062-032F01US 9894 30623 7590 04/21/2020 Mintz Levin/Boston Office One Financial Center Boston, MA 02111 EXAMINER CLARKE, TRENT R ART UNIT PAPER NUMBER 1651 NOTIFICATION DATE DELIVERY MODE 04/21/2020 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): IPDocketingBOS@mintz.com IPFileroombos@mintz.com mintzdocketing@cpaglobal.com PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte MEHMET Z. SENGUN, WILLIAM PARRISH, GREGORY R. WHITTAKER, DOUGLAS A. FIFOLT, and BROOKS J. STORY Appeal 2019-003273 Application 13/250,086 Technology Center 1600 Before DONALD E. ADAMS, ERIC B. GRIMES, and TAWEN CHANG, Administrative Patent Judges. CHANG, Administrative Patent Judge. DECISION ON APPEAL Pursuant to 35 U.S.C. § 134(a), Appellant1 appeals from the Examiner’s decision to reject claims 1, 5–10, 13, 17–20, and 53. We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE. 1 We use the word “Appellant” to refer to “applicant” as defined in 37 C.F.R. § 1.42. Appellant identifies the real party in interest as DePuy Mitek, LLC. Appeal Br. 1. Appeal 2019-003273 Application 13/250,086 2 BACKGROUND According to the Specification, “[u]pon injury to the skin, a set of complex biochemical events takes place in a closely orchestrated cascade to repair the damage. Within minutes post-injury, platelets (thrombocytes) aggregate at the injury site to form a fibrin clot. This clot acts to control active hemostasis.” Spec. ¶ 3. Further according to the Specification, [i]t has been discovered that dimensionally stable, fibrin constructs can be reproducibly obtained from clotted blood and can substantially promote wound healing. For example, fibrin constructs are useful for local administration to a wound site or region. The fibrin constructs can also include components that promote wound healing, such as platelets, growth factors, white blood cells, aggregated fibrin and growth factors and/or other proteins. Spec. ¶ 70. CLAIMED SUBJECT MATTER The claims are directed to a method of reproducibly preparing a growth factor enriched fibrin construct. Claim 1, the only independent claim, is illustrative: 1. A method of reproducibly preparing a growth factor enriched fibrin construct, comprising: (a) collecting a human blood sample comprising unaggregated fibrin, wherein collecting the blood sample comprises exposing the blood sample to an anti-coagulant; (b) mixing the blood sample in a borosilicate glass container with a coagulation activator consisting of a calcium salt to initiate aggregation of the fibrin; (c) exposing the blood mixture to a separation force, thereby producing a dimensionally stable, suturable growth factor enriched fibrin construct comprising a fibrin layer, a platelet layer and a red blood cell layer, wherein said separation force is a single centrifugation with a speed of about 2000g to about 3,000g; Appeal 2019-003273 Application 13/250,086 3 wherein the fibrin construct has a growth factor enriched surface concentrated with blood cells and platelets and an opposed, growth factor depleted surface; wherein the growth factor enriched surface is capable of releasing a growth factor and wherein the released growth factor comprises at least about 5ng of vascular endothelial growth factor (VEGF) within 24 hours. Appeal Br. App. A: Claims on Appeal, A. REJECTION(S)2 A. Claims 1, 5–10, 13, 20, and 53 are rejected under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Harrison,3 Hood,4 Sorvall,5 Thermo Scientific,6 and Ariëns.7 B. Claims 1, 5–10, 13, 17–20, and 53 are rejected under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Harrison, Hood, Ehrenfest,8 Beretta,9 Sorvall, Thermo Scientific, and Ariëns. 2 In the Answer, the Examiner withdrew both of the rejections originally on appeal and issued the two new grounds of rejection discussed herein. Ans. 3, 12. 3 Sophia Harrison et al., Platelet Activation by Collagen Provides Sustained Release of Anabolic Cytokines, 39 AM. J. SPORTS MED. 729 (2011). 4 Hood, III, US 5,733,545, issued Mar. 31, 1998. 5 Kendro Laboratory Products, Sorvall® RC-3C Plus and RC-3B Plus (2000). 6 Thermo Fisher Scientific Inc., Large Capacity Rotors: Thermo Scientific H-12000 Blood Processing Rotor (2010). 7 Robert A.S. Ariëns et al., Role of Factor XIII in Fibrin Clot Formation and Effects of Genetic Polymorphisms, 100 BLOOD 743 (2002). 8 David M. Dohan Ehrenfest et al., Review, Classification of Platelet Concentrates: from Pure Platelet-rich Plasma (P-PRP) to Leucocyte- and Platelet-rich Fibrin (L-PRF), 27 TRENDS IN BIOTECHNOLOGY 158 (2008). 9 Beretta et al., US 7,745,106 B2, issued June 29, 2010. Appeal 2019-003273 Application 13/250,086 4 OPINION A. Issue The Examiner rejects claims 1, 5–10, 13, 20, and 53 as obvious over Harrison, Hood, Sorvall, Thermo Scientific, and Ariëns. The Examiner also rejects claims 1, 5–10, 13, 17–20, and 53 as obvious over Harrison, Hood, Ehrenfest, Beretta, Sorvall, Thermo Scientific, and Ariëns. The same issues are dispositive for both rejections; we therefore discuss them together. The Examiner finds that Harrison suggests almost all of the limitations of claim 1, except that it (1) does not explicitly “specify the centrifugal force provided by their centrifugation step;” (2) does not explicitly teach “a dimensionally stable, suturable growth factor enriched fibrin construct comprising a fibrin layer, a platelet layer and a red blood cell layer,” wherein “the fibrin construct has a growth factor enriched surface concentrated with blood cells and platelets and an opposed, growth factor depleted surface” and wherein “the growth factor enriched surface is capable of releasing a growth factor and . . . the released growth factor comprises at least about 5ng of vascular endothelial growth factor (VEGF) within 24 hours”; and (3) “teaches using bovine thrombin with 10% calcium chloride, and doesn’t teach using calcium chloride as the sole coagulation activator (i.e. a coagulation activator consisting of a calcium salt).” Ans. 5–8 (emphasis added). With respect to the limitation relating to centrifugal force, the Examiner finds that Harrison teaches centrifuging the blood mixture at 2500 rpm in the supernatant extraction step. Ans. 5. The Examiner finds that Harrison uses a Sorvall RC3 centrifuge from Thermo Scientific, which has an “effective radius (r) [of rotation] of 26.26 cm,” which in turn “would Appeal 2019-003273 Application 13/250,086 5 apply a centrifugal force of ~ 1820 x g.” Id. The Examiner further finds that “Harrison is studying how the parameters of clot formation, e.g. platelet concentration and . . . activators, affect the kinetics of growth factor release from the fibrin constructs (clots),” and that a skilled artisan would have found it obvious that centrifugal force used in formation of the fibrin constructs would affect the structure of the fibrin constructs (e.g. greater centrifugal force would produce a more compressed construct) which would affect growth factor release, i.e. centrifugal force is a result effective variable affecting growth factor release from the constructs; hence, the ordinarily skilled artisan would find it obvious to adjust the centrifugal force to optimize the constructs produced and arrive at the claimed invention. Id. at 5–6. With respect to the limitation relating to the amount of VEGF being released within 24 hours by the growth factor enriched surface of the fibrin construct, the Examiner finds that Harrison teaches measuring the amount of VEGF released into 5 ml of blood at 7 different time points and that “the clot from each time point . . . releases about 0.2 ng VEGF/ml,” or 1 ng of VEGF released from each of 7 time points. Ans. 6. The Examiner finds that, accordingly, “a . . . clot not distributed over a time course would be capable of releasing at least 7 ng VEGF in 24 h.” Id. The Examiner also finds, with respect to this limitation and the limitations relating to certain other structural and functional characteristics of the claimed fibrin construct (i.e., “dimensionally stable,” “suturable,” “growth factor enriched,” “comprising a fibrin layer, a platelet layer and a red blood cell layer,” having “a growth factor enriched surface concentrated with blood cells and platelets” capable of releasing a growth factor and “an opposed, growth factor depleted surface”) to be inherently disclosed, Appeal 2019-003273 Application 13/250,086 6 because “the method made obvious by Harrison for producing a therapeutic clot meets all of the positively recited steps of the claimed method.” Ans. 8. Finally, with respect to the limitation regarding “a coagulation activator consisting of a calcium salt,” the Examiner finds that Hood teaches that calcium chloride alone is sufficient . . . for clot formation from human anticoagulated (ACD) plasma-buffy coat concentrate (which comprises white blood cells and platelets and has had red blood cells removed . . .), teaches that no thrombin was added . . . , teaches that the calcium chloride neutralizes the free citrate from the ACD . . . and that the calcium ions alone are sufficient for clot formation. Id. at 7. The Examiner further finds that “Hood teaches ‘[a]n advantage of use of calcium over other techniques for initiating clotting is the absence of need for exogenous thrombin, the source of some number of patient complications.’” Id. (brackets added). The Examiner concludes that, given Hood’s teachings, a skilled artisan would have found it obvious to use “calcium chloride as the sole coagulation activator to initiate aggregation of the fibrin (i.e. wherein the coagulation activator consists of a calcium salt),” in place of the bovine thrombin and calcium chloride taught in Harrison. Ans. 7. Appellant contends among other things that the cited combination of reference do not “disclose or suggest the claimed method of reproducibly preparing a growth factor enriched fibrin construct” that includes at least the step of “exposing the blood mixture to a separation force, thereby producing a dimensionally stable, suturable growth factor enriched fibrin construct comprising a fibrin layer, a platelet layer and a red blood cell layer,” wherein the fibrin construct has the characteristics recited in the claims. Reply Br. 3. Appeal 2019-003273 Application 13/250,086 7 B. Analysis We agree with Appellant that the Examiner has not established a prima facie case that the claims are obvious over the cited prior art. The claims require “exposing the . . . mixture [of a human blood sample and a coagulation activator consisting of a calcium salt] to a separation force, thereby producing a dimensionally stable, suturable growth factor enriched fibrin construct comprising a fibrin layer, a platelet layer and a red blood cell layer, wherein the separation force is a single centrifugation with a speed of about 2000g to about 3,000g.” Appeal Br. App. A: Claims on Appeal, A. The Examiner asserts that the cited prior art combination teaches this limitation because Harrison teaches preparing whole blood and platelet-rich plasma (PRP) samples containing bovine thrombin reconstituted with 10% calcium chloride, allowing the samples to clot, and then extracting “supernatant exuded from [the] clot” by centrifuging the sample at 2500 rpm for 10 minutes. Ans. 5. Based on Harrison’s disclosure that a Sorvall RC3 centrifuge from Thermo Scientific was used to extract the supernatant, the Examiner calculates that the centrifuge would apply 1820g of centrifugal force at 2500 rpm. The Examiner does not assert that 1820g meets the limitation of “about 2000g to about 3,000g.” However, the Examiner finds that centrifugal force is a known result effective variable affecting growth factor release from the constructs and that, therefore, “the ordinarily skilled artisan would find it obvious to adjust the centrifugal force to optimize the constructs produced and arrive at the claimed invention.” Ans. 6. We are not persuaded. While “it is not inventive to discover the optimum or workable ranges by routine experimentation” where “the general Appeal 2019-003273 Application 13/250,086 8 conditions of a claim are disclosed in the prior art,” In re Aller, 220 F.2d 454, 456 (CCPA 1955), the centrifugation in Harrison cited by the Examiner is not used to form a fibrin construct, as recited in the claims, but rather to extract the supernatant exuded from already formed clots. Harrison 3 (supernatant collected at 2 hours and 1, 2, 3, 4, 5, and 6 days after blood sample preparation). Indeed, Harrison explains that, after the supernatant was removed by centrifugation, the tubes containing the clots (i.e., the fibrin construct) were discarded. Id. Thus, the Examiner has not persuasively shown that a skilled artisan would have had reason to adjust the centrifugation speed for purposes of optimizing fibrin constructs rather than to optimize supernatant extraction. For the reasons discussed above, we reverse the Examiner’s rejection of claim 1 as obvious over Harrison, Hood, Sorvall, Thermo Scientific, and Ariëns. Similarly, the Examiner cites Beretta and Ehrenfest only for the additional limitations in dependent claims 17–19 relating to, respectively, blotting, folding, and layering a second fibrin construct on top of the fibrin construct. Ans. 24–25. Accordingly, we reverse the Examiner’s rejection of claim 1 as obvious over Harrison, Hood, Ehrenfest, Beretta, Sorvall, Thermo Scientific, and Ariëns for the same reasons already discussed. We likewise reverse the rejection of claims 5–10, 13, 17–20, and 53, all of which depend from claim 1. In re Fine, 837 F.2d 1071, 1076 (Fed. Cir. 1988) (“Dependent claims are nonobvious under section 103 if the independent claims from which they depend are nonobvious.”). Appeal 2019-003273 Application 13/250,086 9 CONCLUSION In summary: Claims Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1, 5–10, 13, 20, 53 103(a) Harrison, Hood, Sorvall, Thermo Scientific, Ariëns 1, 5–10, 13, 20, 53 1, 5–10, 13, 17–20, 53 103(a) Harrison, Hood, Ehrenfest, Beretta, Sorvall, Thermo Scientific, Ariëns 1, 5–10, 13, 17–20, 53 Overall Outcome 1, 5–10, 13, 17–20, 53 REVERSED Copy with citationCopy as parenthetical citation