Ex Parte Binette et alDownload PDFPatent Trials and Appeals BoardMay 21, 201910638562 - (D) (P.T.A.B. May. 21, 2019) Copy Citation UNITED STA TES p A TENT AND TRADEMARK OFFICE APPLICATION NO. FILING DATE FIRST NAMED INVENTOR 10/638,562 08/11/2003 Francois Binette 30623 7590 05/23/2019 Mintz Levin/Boston 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 ATTORNEY DOCKET NO. CONFIRMATION NO. 4 7062-0 l 3FO lUS (MIT5019US EXAMINER 4823 One Financial Center SWEET, THOMAS Boston, MA 02111 ART UNIT PAPER NUMBER 3774 NOTIFICATION DATE DELIVERY MODE 05/23/2019 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 PTOL-90A (Rev. 04/07) UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte FRANCOIS BINETTE and ED YILING LU1 Appeal2017-011735 Application 10/638,562 Technology Center 3700 Before ERIC B. GRIMES, RICHARD M. LEBOVITZ, and RYAN H. FLAX, Administrative Patent Judges. GRIMES, Administrative Patent Judge. DECISION ON APPEAL This is an appeal under 35 U.S.C. § 134 involving claims to a method of treating a diseased or damaged joint surface, which have been rejected as obvious. We have jurisdiction under 35 U.S.C. § 6(b). We affirm-in-part. STATEMENT OF THE CASE "One common type of tissue injury at the knee joint involves damage to articular cartilage, a non-vascular, resilient, and flexible connective tissue." Spec. ~ 6. "Damaged articular cartilage can severely restrict joint 1 Appellants identify the Real Party in Interest as Depuy Mitek, LLC. Appeal Br. 1. Appeal2017-011735 Application 10/638,562 function, cause debilitating pain and may result in long term chronic diseases such as osteoarthritis." Id. ,r 7. While "current treatments address focal point defects, they are not tailored for treating large surface areas of diseased or damaged tissue ( e.g., cartilage) that occur with the progression of degenerative joint diseases such as osteoarthritis." Id. ,r 10. The Specification discloses a method for resurfacing a large surface area ( e.g., greater than about 10 cm2) such as an entire condyle area where both cartilage and subchondral bone tissues have been affected by degeneration such as by osteoarthritis. More specifically, a method is provided for resurfacing an articular surface of a bone joint by replacing damaged or diseased cartilage tissue with a tissue-engineered construct for growing new cartilage tissue. Id. ,I 13. Claims 1--4, 6, 8-27, 29-33, 35, and 37-39 are on appeal. Claim 1 is illustrative and reads as follows: 1. A method for resurfacing a diseased or damaged articular surface in a patient, comprising the steps of: providing a biocompatible, bioresorbable scaffold, the scaffold comprising a flexible sheet; collecting and mincing living tissue comprising viable cells to form a plurality of minced tissue fragments having an effective amount of said viable cells such that said viable cells can migrate out of the minced tissue fragments and populate the scaffold, the plurality of minced tissue fragments comprising particles in the range from at least about 0.1 mm3 to at least about 3 mm3; immediately following the mincing step, associating the scaffold with at least one of the plurality of minced tissue fragments, wherein the at least one of the plurality of minced tissue fragments is distributed on a surface of the scaffold, thus forming a tissue repair implant; 2 Appeal2017-011735 Application 10/638,562 following the associating, placing at least one layer of a retaining element over at least a portion of the scaffold; preparing the articular surface to receive the tissue repair implant, wherein the surface area of the prepared articular surface is in the range of about 10 cm2 to about 20 cm2; after the placing and immediately after preparing the articular surface, implanting the tissue repair implant onto the prepared articular surface, wherein the scaffold is configured to (i) substantially conform to the prepared articular surface and (ii) substantially cover an entire surface area of the prepared articular surface; and securing the tissue repair implant in place using at least one mechanical biocompatible, fastening agent. DISCUSSION The Examiner has rejected all of the claims on appeal under 35 U.S.C. § I03(a) as obvious based on Rieser,2 Gomes, 3 and Stone. 4 Ans. 2. The Examiner finds that "Rieser discloses a method of resurfacing an articular surface comprising providing a biocompatible, bioabsorbable scaffold comprising a flexible sheet." Id. The Examiner finds that Rieser's scaffold is absorbable because it can be collagen or PLA (poly-lactic acid). Id. The Examiner finds that Rieser also teaches "providing living tissue fragments with an effective amount of viable cells ... and immediately after forming particles, associating the scaffold (7) with live tissue fragments." Id. at 2-3. The Examiner also finds that Rieser teaches, "following the 2 Rieser et al., US 6,242,247 Bl; June 5, 2001. 3 Gomes et al., US 2004/0219182 Al; Nov. 4, 2004. 4 Stone, US 6,110,209; Aug. 29, 2000. 3 Appeal2017-011735 Application 10/638,562 associating, placing a layer of retaining element over a portion of the scaffold (retaining material may be considered top membrane 3 ... )." Id. at 3. The Examiner finds that Rieser teaches preparing the articular surface ... and after placing the retaining element and immediately after preparing the surface, implanting the tissue repair implant on the articular surface ... , and securing the implant in place using at least one mechanical fastener (pins, sutures, fixation means ... ) wherein the steps are all part of one procedure. Id. The Examiner finds that "Rieser does not specifically disclose mincing" tissue to form particles; does not disclose the size of the particles; and "does not disclose a specific surface area of the surface defect." Id. at 3--4. The Examiner finds that Stone discloses mincing tissue to form particles, because it "teaches in the same field of live tissue particles for articular joint repair, wherein the live tissue particles are formed by crushing/morselizing after collection." Id. at 4. 5 The Examiner concludes that it would have been obvious "to combine Rieser's method that makes use of live tissue particles partially isolated/separated from tissue source after collection by known methods, with Stone's teaching crushing/morselizing" because Stone's method was "a known method of live tissue particle formation in the articular cartilage implantation art." Id. With regard to the size of the particles, the Examiner cites "Gomes ... as evidence showing it is known in the field of cartilage/articular surface repair to use particles of the claimed size range." Id. at 5. The Examiner concludes that it would have been obvious "to have Rieser's particles of the 5 Appellants do not dispute that Stone's "crushing/morselizing" is equivalent to the "mincing" recited in claim 1. See Appeal Br. 10--13. 4 Appeal2017-011735 Application 10/638,562 size O. lmm[3]-3mm[3], since such would have been an obvious change in the size of a component (the particles)." Id. at 4--5. Finally, the Examiner finds that "Rieser discloses preparation of an articular surface of a large area ... [but] does not disclose an exact surface area." Id. at 5. The Examiner concludes that it would have been obvious to prepare and cover a 10-20cm[2] surface area, since where[] the general conditions of a claim are disclosed in the prior art ... it would have been an obvious change in size of the prepared surface and implant to make larger (to I0-20cm[2]) in the case that the defected surface was larger, in order to repair the entire area of damage. Id. We agree with the Examiner that the method of claim 1 would have been obvious to a person of ordinary skill in the art based on the cited references. Rieser discloses that "efforts have been made for quite some time to replace or repair missing or damaged cartilage, especially articular cartilage by corresponding surgery." Rieser 1 :38--40. Rieser states that previous methods "attempt to produce cartilage at least partly in vitro .... The problem encountered in these attempts is the fact that chondrocytes in these in vitro conditions have the tendency to de-differentiate into fibroblasts relatively rapidly." Id. at 3:3-8. Rieser discloses that "implants produced according to [its] invention consist at least partly of cartilage tissue produced in vitro and are especially suited for the repair of enchondral or osteochondral joint defects." Id. at 3 :44--4 7. In Rieser' s method, "cells which are capable of a chondrocyte- function are introduced into an empty cell space, i.e. into a space containing culture medium only, such that there is a cell density of ca. 5xl 07 to 109 cells 5 Appeal2017-011735 Application 10/638,562 per cm3 in the cell space." Id. at 4:22-26. Rieser's Figure 2 is reproduced below: 3 2 l FIG. 2 7 FIG. 2 shows a further embodiment of a cell space for carrying out the inventive method. The cell space 1 is flat and its one side is limited by an open pore, rigid or plastically deformable plate 7 made of a possibly biologically degradable bone substitute material, the other side by a permeable wall, e.g. a semi-permeable membrane 3. Rieser 7:7-12. Figure 2 also shows culture medium space 2. Id. at 6:29. The bone substitute material for plate 7 is a "known osteo-inductive and/or osteo- conductive material[]. ... Plastically deformable plates can e.g. be produced from collagen I, from collagen II and hydroxyapatite or from poly-lactic acid." Id. at 8: 17-23. Rieser states that [t]he cells to be brought into the cell space are chondrocytes, mesenchymal stem cells or other mesenchymal cells. These cell types are isolated in known manner from cartilage tissue, from bone or bone marrow or from connective tissue or fatty tissue. It is not necessary to isolate specific cell types from donor tissue, i.e. mixtures of different cells as usually contained in such tissues can be brought into the cell space as such. It also shows that a complete separation of the cells from the intracellular matrix of the donor tissue is not necessary and thus 6 Appeal2017-011735 Application 10/638,562 possibly tissue particles or mixtures of isolated cells and tissue particles can be brought into the cell space instead of cells only. Id. at 5: 15-33. Rieser teaches that "the cell space 1 is e.g., as shown in FIG. 2, arranged to be stationary with the bone substitute plate 7 facing downward such that the cells settle on the bone substitute plate 7 due to the effect of gravity." Id. at 7:30-33. Thus, "the cells settle over the whole inner surface of the bone substitute plate 7." Id. at 7:27-28. Rieser teaches that, after "[ c Jells, tissue particles or mixtures of cells and/or tissue particles ... are suspended e.g. in culture medium and are introduced into the free cell space," "[t]he cell space is closed and introduced into the culture medium space." Id. at 6:56-64. That is, the cell space 1 between bone substitute plate 7 and semi-permeable membrane 3 is closed after the suspension of tissue particles in culture medium is introduced. Rieser teaches preparing the articular surface of both enchondral and osteochondral defects for implantation of its implants, and implanting the implant on the prepared articular surface. Id. at 10:51---61, 11:3-9. Rieser teaches securing the implant with mechanical fasteners such as pins or sutures. Id. at 10:62 to 11:2, 11:9-16. Thus, Rieser expressly discloses or makes obvious a method of resurfacing a damaged articular surface that includes providing a plastically deformable, biologically degradable bone substitute material (i.e., a scaffold), collecting donor tissue and producing tissue particles comprising viable cells, associating the scaffold with the tissue particles by distributing the particles on the scaffold, placing a semipermeable membrane (i.e., a retaining element) over the scaffold, preparing the articular surface, 7 Appeal2017-011735 Application 10/638,562 implanting the implant on the prepared surface, and securing the implant using a mechanical fastening agent. Rieser does not teach that tissue is minced to produce tissue particles for use in its method, but Stone teaches a method for repairing an arthritic joint comprising removing a graft of osteocartilaginous tissue, which is "then placed into a graft crushing device, such as a press, where it is crushed, or morselized, to form a paste-consistency agglomerate ( a 'tissue paste') of crushed cancellous bone and mixed articular cartilage." Stone 2:60 to 3: 5. In addition, Gomes discloses using a "matrix of minced cartilage putty consisting of minced or milled cartilage" to make a cartilage implant material. Gomes ,r,r 19, 38. Gomes also teaches that the "cartilage is milled to a size ranging from 0.01 mm to I mm." Id. ,r 38. Based on the teachings of Stone and Gomes, therefore, it would have been obvious to practice Rieser' s method using tissue particles produced by mincing a sample of cartilage tissue to fragment of 0.1 mm3 to 3 mm3 because both Stone and Gomes teach making cartilage particles by mincing ( or crushing/morselizing) and Gomes teaches that similar-sized tissue particles are used to form a cartilage implant material. Appellants argue that claim 1 "indicates that the scaffold is associated with minced tissue fragment( s) and that after this associating at least one layer of a retaining element is placed over the scaffold." Appeal Br. 5. Appellants argue that "Rieser fails to teach or suggest that the permeable membrane 3 is placed over at least a portion of the plate 7 after the cells/tissue particles of Rieser are associated with the plate 7." Id. at 6. Appellants argue that Rieser' s membrane 3 cannot correspond to the retaining element of the claims because Rieser's 8 Appeal2017-011735 Application 10/638,562 Id. Figures 2 and 3 each illustrate arrangements including "a defined cell space 1 into which the cells are introduced." Rieser, col. 6, lines 26-29; see also col. 5, lines 65----67; col. 7, lines 7- 8; col. 8, lines 33-34. In other words, the permeable membrane 3 and the plate 7 are already assembled in place before any cells/tissue particles are introduced into the cell space 1. Otherwise, the cell space 1 would not be "defined." This argument is unpersuasive because Rieser expressly describes closing the cell space after introducing tissue particles into it: "[T]issue particles ... are suspended e.g. in culture medium and are introduced into the free cell space .... The cell space is closed and introduced into the culture medium space." Rieser 6:58----64. That is, as discussed above, cell space 1 between bone substitute plate 7 and semi-permeable membrane 3 is closed after the suspension of tissue particles in culture medium is introduced. Appellants also argue that the cited references do not teach or suggest the "collecting and mincing" step of claim 1. Appeal Br. 10. Appellants argue that Stone's tissue paste is "a standalone defect repair element, i.e., no scaffold is used with the paste," whereas Rieser's method introduces tissue particles into a cell space to be cultured. Id. at 12. For the same reason, Appellants argue that combining Stone's tissue paste with Rieser's method would remove the claimed "associating" step from Rieser. Id. at 15. Appellants argue that Rieser teaches away from Stone's paste because it "indicates that the dense culture or matrix such as Stone's paste formed by crushing/morselizing is unsatisfactory because it does not have 'a stability which could withstand even a greatly reduced strain."' Id. at 12-13. Finally on this point, Appellants argue that modifying Rieser's method according to 9 Appeal2017-011735 Application 10/638,562 Stone would completely change the operability of Rieser, because Stone's tissue paste is delivered immediately to a defect site, not cultured for a period of weeks. Id. at 13-14. These arguments are unpersuasive because the Examiner relies on Stone only for its disclosure of a method of making tissue particles from a sample of tissue. See Ans. 4. That is, "Rieser discloses isolating or partially isolating/separating cells from their source (such as bovine shoulder ... )," while Stone teaches "crushing/morselizing ... to be a known method of processing live tissue to create live tissue particles." Id. We agree with the Examiner that, based on these teachings, it would have been obvious to use "morselizing," as taught by Stone, to create tissue particles for use in Rieser's method because Gomes teaches that particles of this type are useful for implant materials (Gomes ,r,r 19, 38). In addition, the Examiner cited Gomes' disclosure of "minced cartilage putty consisting of minced or milled allograft articular cartilage." Ans. 4--5 ( citing Gomes ,r 38). Thus, Gomes provides additional evidence that mincing a tissue sample was a known method of forming tissue particles. Appellants argue that the cited references do not disclose the particle size recited in claim 1. Appeal Br. 15-16. Appellants argue that the Examiner improperly relies on "routine optimization to obtain the fragment size range recited in claim 1 because none of the cited references recognize the parameter of particle size as a result effective variable." Id. at 16. Specifically, Appellants argue that "Gomes mentions in conclusory fashion a size of minced or milled cartilage as having 'a size ranging from 0.01 mm to 1.0 mm' without providing any indication that the size achieves any recognized result." Id. 10 Appeal2017-011735 Application 10/638,562 This argument is unpersuasive. Claim 1 recites tissue particles in the size range of 0.1-3 mm3• Gomes teaches cartilage tissue particles in the range of O.01 mm to 1 mm. Gomes ,r 3 8. Appellants do not dispute that Gomes' range overlaps the claimed range. 6 "A prima facie case of obviousness typically exists when the ranges of a claimed composition overlap the ranges disclosed in the prior art." In re Peterson, 315 F.3d 1325, 1329 (Fed. Cir. 2003). The cited references therefore support a prima facie case of obviousness. However, a prima facie case of obviousness based on overlapping ranges "can be rebutted if the applicant (1) can establish 'the existence of unexpected properties in the range claimed' or (2) can show 'that the art in any material respect taught away' from the claimed invention." In re Geisler, 116 F.3d 1465, 1469 (Fed. Cir. 1997). Appellants argue that the Hwang Declaration indicates that particles of the claimed size range yielded unexpected results. In particular, it was discovered that tissue fragments greater than 3 mm3 were not capable of uniformly filling the scaffold on which they were implanted .... Also, tissue fragments with volumes less than 1 mm3 unexpectedly showed a reduction in the number of cells migrating from the minced tissue and proliferating in the scaffold. Appeal Br. 1 7. The Hwang Declaration states that, 6 The Hwang Declaration (Declaration under 3 7 C.F .R. § 1.13 2 of Julia Hwang, filed Jan. 9, 2009) states that a cartilage sample 2 mm in diameter and 1 mm thick has a volume of 3 mm3. Hwang Deel. ,r 6. Appellants do not dispute that a cartilage particle 1 mm in diameter also has a volume within the range recited in claim 1. 11 Appeal2017-011735 Application 10/638,562 when constructs formed from 7mm3 tissue fragments and a scaffold were implanted on the back of SCID mice, the implants did not exhibit an uniform fill with cartilaginous tissue .... Unexpectedly, only fragments 3mm3 and smaller exhibited uniformly filled cartilaginous tissue. We therefore concluded that fragments 3mm3 and smaller would be mostly likely to result in successful regeneration of cartilage tissue when delivered to the site of cartilage injury in a joint. Hwang Declaration ,r 7. The Hwang Declaration also states that fragments with a volume less than about .004mm3 unexpectedly showed a reduction in the number of cells migrating from the minced tissue and proliferating in the scaffold .... We therefore concluded that only minced tissue fragments with a volume greater than about .004mm3 would be acceptable for successful regeneration of cartilage tissue when delivered to the site of cartilage injury in a joint. Id. ,I 8. The Hwang Declaration, therefore, states that tissue fragments of 3 mm3 are unexpectedly superior to tissue fragments of 7 mm3 and 0.004 mm3. The closest prior art, however, teaches tissue particles in the range of 0.01 mm to 1 mm. Gomes ,r 3 8 (see footnote 6, above). Appellants' evidence thus does not show unexpectedly superior results for the size range recited in the claims, i.e., at least about 0.1 mm3 to at least about 3 mm3, compared to the closest prior art. See In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991) ("[W]hen unexpected results are used as evidence of nonobviousness, the results must be shown to be unexpected compared with the closest prior art."). For the reasons discussed above, we affirm the rejection of claim 1 under 35 U.S.C. § 103(a) based on Rieser, Gomes, and Stone. Appellants' arguments with respect to independent claim 31 (Appeal Br. 23) are the same as for claim 1, and are unpersuasive for the same reasons. Claims 2--4, 12 Appeal2017-011735 Application 10/638,562 6, 8-15, 22-27, 30, 32, 33, 35, and 37-39 were not argued separately and therefore fall with claims 1 and 31. 37 C.F.R. § 4I.37(c)(l)(iv). With respect to dependent claims 16-18 and 29, Appellants argue that the Examiner addresses all of the dependent claims in a single paragraph of the rejection and does not identify where the limitations of claims 16-18 and 29 are taught in the cited references. Appeal Br. 18-20, 22-23. We agree with Appellants that the Examiner has not shown that claims 16-18 would have been obvious based on the cited references. As Appellants pointed out, the Examiner's rejection addresses all of the dependent claims in a single paragraph (Ans. 6) and does not identify any disclosure in the references of the specific limitations recited in claims 16- 18 or 29. While the Examiner responded to Appellants' arguments (id. at 12-13), the Examiner did not cite sufficient evidence to show that platelets and collagen are naturally present in Rieser' s tissue particles and did not provide Appellants a fair opportunity to respond to a new interpretation of claim 29. We therefore reverse the rejection of claims 16-18 and 29. With respect to dependent claims 19-21, Appellants argue that "Rieser is completely silent as to an adhesion agent for anchoring a suspension of tissue fragments to a biocompatible scaffold," as recited in claim 19. Appeal Br. 21. Rather, Appellants argue, Rieser discloses that "fibrin glue is used to glue the implant to the patient. The fibrin glue thus clearly does not anchor a suspension of tissue fragments to a biocompatible scaffold." Id. We agree with Appellants' argument regarding claim 19 ( and claims 20 and 21, which depend from claim 19), which requires that "the biocompatible scaffold further comprises an adhesion agent for anchoring a 13 Appeal2017-011735 Application 10/638,562 suspension of tissue fragment to the biocompatible scaffold." Claim 19. The Examiner finds that "Rieser ... discloses additional biological components such as growth factors, cells, adhesives such as fibrin, cement, collagen etc (col.5, lines 15-23, 39-43; col.11, line 1)." Ans. 6. As relevant to claim 19, Rieser describes "fibrin glue." Rieser 11: 1. As Appellants point out, however, that description is in the context of "a glue being introduced between native cartilage and implant" to fix the implant used to repair a larger defect. Id. at 10:62 to 11:1. The Examiner responds that Rieser teaches fibrin glue, and also "discloses the particles/ cells to be in cell space which would be exposed to light and ph, which are claimed cross-linking agents," as recited in claim 21. Ans. 13. The Examiner's reasoning, however, does not persuasively explain how Rieser's description of fibrin glue, or the light or pH to which its tissue particles would be exposed, teaches or suggests the use of any of these agents for anchoring a suspension of tissue fragments to a biocompatible scaffold. We therefore reverse the rejection of claims 19-21. SUMMARY We affirm the rejection of claims 1--4, 6, 8-15, 22-27, 30-33, 35, and 37-39 under 35 U.S.C. § 103(a) based on Rieser, Gomes, and Stone. We reverse the rejection of claims 16-21 and 29 under 35 U.S.C. § 103(a) based on Rieser, Gomes, and Stone. 14 Appeal2017-011735 Application 10/638,562 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-IN-PART 15 Copy with citationCopy as parenthetical citation