Hani Awad et al.Download PDFPatent Trials and Appeals BoardDec 16, 20212020003297 (P.T.A.B. Dec. 16, 2021) 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. 15/444,445 02/28/2017 Hani Awad 1903-0001CNT1 5723 28078 7590 12/16/2021 MAGINOT, MOORE & BECK, LLP One Indiana Square, Suite 2200 INDIANAPOLIS, IN 46204 EXAMINER FOX, ALLISON M ART UNIT PAPER NUMBER 1633 MAIL DATE DELIVERY MODE 12/16/2021 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 HANI AWAD, BRADLEY T. ESTES, and FARSHID GUILAK Appeal 2020-003297 Application 15/444,445 Technology Center 1600 Before JOHN G. NEW, TAWEN CHANG, and RACHEL H. TOWNSEND, 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 1–20. We have jurisdiction under 35 U.S.C. § 6(b). We AFFIRM IN PART. 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 Cytex Therapeutics, Inc. Appeal Br. 2. Appeal 2020-003297 Application 15/444,445 2 STATEMENT OF THE CASE The Specification states that prior art has shown “the potential for the induction of bone in ectopic sites such as muscle by the implantation of demineralized bone powder.” Spec. ¶ 3. The Specification states, however, that “a similar approach is not available for the repair of soft tissues” and that “[t]he current state of the art typically involves the use of autologous tissue grafts, cryo-preserved or fresh allograft tissues, or the use of synthetic (metal, polymer) . . . materials” as functional tissue replacements for missing or damaged tissues. Id. ¶¶ 4–5. The Specification describes significant drawbacks for each of the current tissue replacement materials. Id. ¶¶ 5–6. According to the Specification, “[t]he present invention relates to the repair, replacement and/or regeneration of diseased or traumatized soft tissue.” Spec. ¶ 2. More particularly, the Specification states that invention relates to process[ing] soft tissue from specific sites in the body in a manner that produces pulverized morsels of the soft tissue [(Native Soft Tissue Matrix or NSTM)] devoid of immunogenic material and pathogens but with intact aspects of the composition of the extracellular matrix proteins including the growth factors and cytokines that are responsible for tissue growth and cellular infiltration and differentiation. Id. ¶ 7. The Specification further states that the invention introduces use of NTSM morsels “that can be used either as an acellular (non-viable) filler material or combined with viable elements (cells) and/or bioactive molecules to promote the repair or regeneration of diseased or traumatized soft tissues.” Id. ¶ 9. Appeal 2020-003297 Application 15/444,445 3 CLAIMED SUBJECT MATTER The claims are directed to a method for preparing a product for use in repairing a lesion or defect at a tissue site in a human or animal patient body, a product produced according to such a method, a method for repairing such a lesion or defect, and a product for introduction within such a tissue site. Claims 1, 13, and 20 are illustrative: 1. A method for preparing a product for use in repairing a lesion or defect at a tissue site in a human or animal patient body, the method comprising: [(a)] obtaining tissue from a donor human or animal body; [(b)] freezing the obtained tissue; [(c)] pulverizing the frozen tissue; [(d)] suspending the pulverized tissue in a fluid; [(e)] homogenizing the tissue suspension using a tissue homogenizer; [(f)] precipitating tissue particles from the homogenized tissue suspension; [(g)] re-suspending the precipitated tissue particles; and [(h)] lyophilizing the tissue re-suspension to provide the product to be used in repairing the lesion or defect. 13. A product produced according to the method of claim 1. 20. A product for introduction within a tissue site of the human or animal body, the product comprising: a matrix of a substantially non-mineralized native soft tissue of the human or animal body, the matrix including a plurality of pores, the matrix formed by lyophilizing a tissue suspension, wherein: the tissue suspension includes precipitated tissue particles suspended in a fluid, the precipitated tissue particles are tissue particles precipitated from a homogenized tissue suspension, the homogenized tissue suspension is a homogenization of pulverized tissue homogenized using a tissue homogenizer and suspended in a second fluid, and Appeal 2020-003297 Application 15/444,445 4 the pulverized tissue is frozen tissue obtained from a donor human or animal body that has been pulverized. Appeal Br. 33, 35, 37 (Claims App.) (bracketed alphabetical notations added). REJECTION(S) A. Claims 1–20 are rejected under pre-AIA 35 U.S.C. § 103(a) as being unpatentable over Hiles.2 Ans. 9. B. Claims 13 and 20 are rejected under pre-AIA 35 U.S.C. § 102(b) as being anticipated by Hiles. Ans. 7. C. Claim 13 is rejected under each of pre-AIA 35 U.S.C. § 102(a) and 35 U.S.C. § 102(e) as being anticipated by Gertzman.3 Ans. 8. D. Claim 13 is rejected under each of pre-AIA 35 U.S.C. § 102(a) and 35 U.S.C. § 102(e) as being anticipated by Lin.4 Ans. 9. OPINION A. Claim Construction We begin our analysis with claim construction. During prosecution, we interpret terms in a claim using the broadest reasonable interpretation in light of the Specification. In re Morris, 127 F.3d 1048, 1055 (Fed. Cir. 1997). 2 Hiles et al., US 2002/0099448 A1, published July 25, 2002. 3 Gertzman et al., US 2003/0206937 A1, published Nov. 6, 2003. 4 Lin et al., US 2004/0091462 A1, published May 13, 2004. Appeal 2020-003297 Application 15/444,445 5 1. Claim 1 preamble Claim 1 recites in its preamble “[a] method for preparing a product for use in repairing a lesion or defect at a tissue site in a human or animal patient body.” Appeal Br. 33 (Claims App.). The Examiner and Appellant appear to agree that the preamble is limiting, at least to a degree. However, the Examiner asserts that the preamble encompasses any product capable of “being placed in a lesion or defect at a tissue site in a human or animal patient body” without causing further damage, Ans. 3, whereas Appellant asserts that the preamble limits the claim to products capable of “being retained in a tissue defect or lesion sufficient to repair the defect or lesion,” Appeal Br. 5. Accordingly, in the context of claim 13 (claiming “[a] product produced according to the method of claim 1”), the Examiner asserts that the product may be a loose powder, Ans. 6, whereas Appellant contends that the claim excludes a loose powder, because “there is nothing to hold the powder at the site.” Id. We are not persuaded by either construction. We agree that the preamble of claim 1 is limiting. However, we find the constructions proposed by the Examiner and the Appellant to be inconsistent with the language of the preamble. More specifically, the claim recites a method for preparing a product for use in “repairing a lesion or defect at a tissue site in a human or animal patient body.” The plain and ordinary meaning of “repairing”5 requires more than not causing further damage; thus we find the Examiner’s proposed construction to be unreasonably broad. On the other 5 “repair.” MERRIAM-WEBSTER, https://www.merriamwebster.com/ dictionary/repair (last visited Dec. 2, 2021) (“to restore to a sound or healthy state”). Appeal 2020-003297 Application 15/444,445 6 hand, the claim does not require the product prepared by the claimed method to be used alone: For instance, the claims do not preclude use of devices (e.g., bandages) that would retain a loose powder at a tissue site so as to allow it “to be used in repairing” a lesion or defect as recited in the body of the claim. Thus, Appellant’s proposed construction, which purports to exclude loose powder, is unduly narrow. Accordingly, we construe the preamble of claim 1 as requiring preparation of a product capable of being used in “repairing a lesion or defect at a tissue site in a human or animal patient body.” 2. “Homogenizing . . . using a tissue homogenizer” Claim 1 recites step (e), “homogenizing the tissue suspension using a tissue homogenizer.” The Examiner concludes: The broadest reasonable interpretation of “homogenizing” is “to blend into a mixture that is the same throughout” . . . , based on definition from Merriam-Webster’s dictionary: “homogenize” 1a: to blend (diverse elements) into a mixture that is the same throughout). There is no explicit definition for “tissue homogenizer” in the specification[;] thus, the broadest reasonable interpretation of [“]tissue homogenizer[”] is considered to be any machine capable of disrupting physical material,[6] based on Sigma-Aldrich “Tissue Homogenizer” Labware Products directory/description. Thus, the step [of] [“homogenizing the tissue suspension using a tissue homogenizer”] is interpreted as requiring blending a tissue suspension into a mixture that is the same throughout using a machine capable of disrupting the physical tissue material. It is noted that the claim requires homogenization of a tissue suspension (tissue is already particulated), the claim does not 6 We understand the Examiner’s construction of “tissue homogenizer” to also include the requirement that the machine be “capable of homogenizing tissue particles in a suspension.” Non-Final Act. 3 (Apr. 4, 2019). Appeal 2020-003297 Application 15/444,445 7 require the homogenization to actually comminute, shear, particulate or modify the actual tissue. Ans. 3–4. Citing to the Estes Declaration,7 Appellant contends that “[t]he Examiner’s interpretation of ‘tissue homogenizer’ essentially reads this limitation out of the claim” and “is contrary to the understanding of a ‘tissue homogenizer’ by the person of ordinary skill in the relevant art.” Appeal Br. 6. Appellant contends that, instead, [a] tissue homogenizer, according to the ordinary and customary meaning given the term by persons of ordinary skill in the relevant art, is a device used to uniformly mince or fragment a tissue in such a manner as to disperse fragments of the tissue evenly throughout a mixture, in which the tissue is torn with high shear forces and is homogenized into similarly sized fragments that are distributed uniformly throughout the solution. Id. at 8; see also id. at 7. We agree with the Examiner that the broadest reasonable interpretation of “homogenizing the tissue suspension using a tissue homogenizer” is to “blend[] a tissue suspension into a mixture that is the same throughout using a machine capable of disrupting the physical tissue material,” for the reasons set forth in the Answer. Ans. 4. We acknowledge Dr. Estes states in his declaration that “[a] tissue homogenizer is a device used to uniformly mince a tissue in such a manner as to disperse fragments of said tissue evenly throughout a mixture.” Estes Decl. ¶ 16. As an initial matter, however, this is uncorroborated testimony of a named inventor, and we are inclined to give such evidence less weight. 7 Declaration of Inventor Bradley T. Estes Pursuant to 37 C.F.R. § 1.132 (Jan. 2, 2019). Appeal 2020-003297 Application 15/444,445 8 See In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1368 (Fed. Cir. 2004) (citations omitted) (explaining that the Board is entitled to weigh the declarations and conclude the lack of factual corroboration warrants discounting the opinions expressed in the declarations). Moreover, it is unclear how Dr. Estes’ definition of a tissue homogenizer differs significantly from the Examiner’s construction (i.e., a machine capable of disrupting the physical tissue material and blending a tissue suspension into a mixture that is the same throughout). We further acknowledge Dr. Estes’ testimony that the tissue homogenizer used by the inventors is “a rotor-stator tissue homogenizer” and that [t]his type of tissue homogenizer utilizes a rapidly rotating blade (rotor) within a static sleeve (stator). When spun at high velocities, the tissue is brought into the end of the sleeve at which time the tissue is torn with high shear forces due to the narrow gap between the rotor and stator. The stators also have saw-tooth end profiles to help shred the tissue apart. While spinning at high RPMs, the tissue is sheared and then pumped out of the holes in the stator. Since the homogenizer is working in an open configuration, the product is recirculated until the material is sufficiently homogenized into similarly sized fragments while the fragments are also being distributed uniformly throughout the solution. Estes Decl. ¶ 16. As evident from the paragraph reproduced above, however, Dr. Estes’ testimony does not suggest that all tissue homogenizers tear tissue with high shear force. Estes Decl. ¶ 16. Rather, Dr. Estes merely states that a particular type of tissue homogenizer used by the inventor (i.e., a rotor-stator tissue homogenizer) tears the tissue with high shear force when the tissue is spun at high velocities. Id. Appellant’s claim does not require a particular Appeal 2020-003297 Application 15/444,445 9 type of tissue homogenizer, just using “a tissue homogenizer.” It is well settled that we will not read into the claim a limitation not present in the claim itself. Bayer AG v. Biovail Corp., 279 F.3d 1340, 1348 (Fed. Cir. 2002). Accordingly, we are not persuaded by Appellant’s argument that the Examiner’s construction of “tissue homogenizer” is unduly broad. 3. Steps (d)-(g) of Claim 1 The Examiner notes that the tissue particles in suspension after step (g) are not clearly different than the tissue particles in suspension after step (d). Steps (e)-(g), while required as active steps in the method, do not necessarily achieve any change or transformation in the tissue particles vis-à-vis step (d), the particles are (d) suspended and (e) homogenized in a fluid, (f) separated from the fluid, and then (g) re-suspended in a fluid (the fluid may be the same or different than the fluid of step (d)). All-in-all, in carrying out steps (d)-(g) results in suspension of tissue particles in a fluid. Ans. 4. Appellant contends that “[t]he Examiner’s understanding regarding the nature of the tissue in steps (d) and (g) is incorrect because the Examiner’s definition of ‘tissue homogenizer’ is incorrect.” Appeal Br. 10. We are not persuaded for the same reasons discussed above with respect to the construction of the term “tissue homogenizer.” B. Obviousness rejection over Hiles (claims 1–20) 1. Issue The Examiner finds that Hiles discloses “medical products for implantation comprising submucosa . . . in various forms, including sheets, sponges, and fluidized.” Ans. 10. The Examiner finds that Hiles teaches methods of preparing its implants that disclose all of the steps of the claimed methods, except that Hiles does not teach “a step of (c) pulverizing the Appeal 2020-003297 Application 15/444,445 10 frozen tissue prior to comminuting the tissue in a blender” and also “does not exemplify all steps together in a single embodiment.” Id. at 10–11. The Examiner finds, however, that the pulverizing step “is a duplication of the cutting/mincing step.” Ans. 10. The Examiner asserts that “[t]he inclusion of an additional reduction in size step would not add significantly more to the claim, and thus is prima facie obvious to duplicate as much as necessary to achieve the desired size.” Id. at 10–11. The Examiner also finds that, although Hiles does not include an embodiment exemplifying all claimed steps together, the rejection is based on selection of a particular comminuting method (i.e., blending a solution of SIS tissue in a high speed blender) from various methods disclosed in Hiles “for use in production of a solid-state article (sponge) via the method of Example 11 in the reference.” Id. at 11. The Examiner asserts that “[s]election of any one of the disclosed comminution methods is considered prima facie obvious, in light of their disclosure as suitable means for comminuting tissue within the reference.” Id. Appellant contends that Hiles does not disclose a method comprising all of the claimed steps in the sequence recited. Appeal Br. 27. The issue with respect to this rejection is whether a preponderance of evidence of record supports the Examiner’s conclusion that the claims are obvious over Hiles. 2. Findings of Fact 1. Hiles teaches the use of “biomaterial comprising the submucosa of a tissue” as implants and in “topical applications . . . such as wound dressings or wound plugs.” Hiles ¶ 5; see also id. ¶¶ 19, 47 (teaching that “[f]luidized tela submucosa of [Hiles’] invention finds use as an injectable Appeal 2020-003297 Application 15/444,445 11 heterograft for tissues . . . in need of repair or augmentation most typically to correct trauma or disease-induced tissue defects” as well as “a filler for implant constructs,” wherein “tela submucosa” refers to “a layer of collagen- containing connective tissue occurring under the mucosa in most parts of the alimentary, respiratory, urinary, integumentary, and genital tracts of animals”), ¶ 52 (teaching “inject[ion of] . . . fluidized submucosa composition into the locale of a tissue defect or a wound in need of healing” to “take advantage of the biotropic properties of the tela submucosa”), ¶ 72 (teaching the use of a lyophilized small intestine submucosa (SIS) sponge for “providing hemostasis in a large wound[,] fill[ing] a large defect[, and/or] provid[ing] a three dimensional structure for cell culture or in vivo growth”). 2. Hiles teaches obtaining “[a] tela submucosa implantable collagen biomaterial according to [its] invention . . . from the alimentary, respiratory, urinary, integumentary, or genital tracts of animals.” Hiles ¶ 25. 3. Hiles teaches that “[p]rocesses of the invention desirably involve first rinsing the tela submucosa source one or more times with a solvent, suitably water,” treating with a disinfecting agent, and delaminating the tela submucosa layer from its source, e.g., intestine. Id. ¶¶ 28, 40. 4. Hiles teaches that the “[t]ela submucosa tissue of [its] invention can also be processed to provide fluidized compositions.” Hiles ¶ 46. In particular, Hiles teaches that solutions or suspensions of the tela submucosa can be prepared by comminuting and/or digesting the tela submucosa with a protease (e.g. trypsin or pepsin), for a period of time sufficient to solubilize the tissue and form substantially homogeneous solution. The submucosa starting material is desirably comminuted by tearing, cutting, grinding, shearing or the like. Appeal 2020-003297 Application 15/444,445 12 Grinding the submucosa in a frozen or freeze-dried state is advantageous, although good results can be obtained as well by subjecting a suspension of pieces of the submucosa to treatment in a high speed blender and dewatering, if necessary, by centrifuging and decanting excess waste. The comminuted tela submucosa can be dried, for example freeze dried, to form a powder. Thereafter, if desired, the powder can be hydrated, that is, combined with water or buffered saline and optionally other pharmaceutically acceptable excipients, to form a fluid tissue graft composition, e.g. having a viscosity of about 2 to about 300,000 cps at 25EC. The higher viscosity graft compositions can have a gel or paste consistency. Id. ¶ 46; see also id. ¶ 49 (describing methods of comminuting tela submucosa specimens), ¶ 50 (teaching that tela submucosa powder “can be easily hydrated using, for example, buffered saline to produce a fluidized tissue graft material of [Hiles’] invention at the desired viscosity”). 5. Hiles teaches that tela submucosa may first be reduced to small pieces, e.g., by cutting before being comminuted while in the frozen state to form a coarse tela submucosa powder. Hiles ¶ 48. 6. Hiles teaches that “[f]urther grinding of the tela submucosa powder using a prechilled mortar and pestle can be used to produce a consistent, more finely divided product” and that “liquid nitrogen is used as needed to maintain solid frozen particles during final grinding.” Hiles ¶ 50. 7. Hiles teaches a method of preparing a preferred fluidized material wherein a tela submucosa powder is “subjected to proteolytic digestion to form a substantially homogeneous solution” and “[t]he solubilized submucosa can then be concentrated by salt precipitation of the Appeal 2020-003297 Application 15/444,445 13 solution and separated for further purification and/or freeze drying to form a protease-solubilized intestinal submucosa in powder shape.” Hiles ¶ 51. 8. Example 11 of Hiles teaches preparation of a lyophilized small intestine submucosa (SIS) sponge wherein comminuted SIS (with a mean particle size of approximately 150 μm) was centrifuged in a Beckman TJ-6 centrifuge with a speed of 1550xg for 15 minutes. The supernatant was poured off leaving a dough-like consistency of SIS remaining. The material was then poured into various polycarbonate molds and frozen at cold temperatures, preferably at -80° C. for at least 2 hours. The material was then vacuum-dried for 6 hours in a lyophilizing system with the condenser at -70° C. at a vacuum pressure of less than 100 millitorr, preferably 15 millitorr. Optionally, the sponge 10 can then be sterilized using ethylene oxide. The resulting structure was an SIS sponge 10, having a creamyish yellow- white color. . . . Using comminuted hydrated SIS with a possible fragment size of 25 to 3000 μm produced a more condensed, higher density sponge, whereas larger fragments produced a less dense larger pore sized sponge. . . . Since the resulting sponge can take the shape of the mold in which it is placed, modifying the mold shape will modify the sponge shape. Hiles ¶¶ 70–71. 9. Hiles teaches that the procedure described in Example 11 may be varied by, e.g., using comminuted hydrated SIS with different fragment sizes. Hiles ¶ 71. 3. Analysis a) Claims 1–12 and 14–19 We agree with Appellant that the Examiner has not established a prima facie case that Hiles renders obvious the methods recited in claims 1– 12 and 14–19 on appeal. In particular, although we agree with the Examiner Appeal 2020-003297 Application 15/444,445 14 that Hile’s method suggests all of the other steps of the claim,8 we agree with Appellant that the Examiner has not established that Hiles discloses or suggests the step in claim 1 of “lyophilizing the tissue re-suspension to 8 Hiles teaches using biomaterial that comprises the submucosa of a tissue from, e.g., the alimentary, respiratory, urinary, integumentary, and/or genital tracts of animals in its method, FF2, which meets step (a) of claim 1, i.e., “obtaining tissue from a donor human or animal body.” Hiles also teaches comminuting the submucosa starting material “by subjecting a suspension of pieces of the submucosa to treatment in a high speed blender and dewatering, if necessary, by centrifuging and decanting excess waste.” FF4. We agree with the Examiner that this teaching reads on step (d) “suspending . . . tissue in a fluid” (i.e., “suspension of pieces of the submucosa”); step (e) “homogenizing the tissue suspension using a tissue homogenizer” (i.e., “treatment in a high speed blender”); and step (f) “precipitating tissue particles from the homogenized tissue suspension” (i.e., “dewatering, if necessary, by centrifuging and decentering excess waste”). Ans. 10. Finally, Example 11 of Hiles teaches using comminuted hydrated SIS to prepare its lyophilized SIS sponge, which suggests re-suspension of the precipitated tissue particles (step (g)). FF8. Likewise, although Hiles does not explicitly provide an example where the tissue was frozen and pulverized (i.e., steps (b) and (c) of claim 1) before being suspended in a fluid and homogenized, Hiles teaches that tela submucosa “may first be reduced to small pieces, e.g., by cutting before being comminuted while in the frozen state to form a coarse . . . powder,” and then further grounded in a frozen state to “produce a consistent, more finely divided product.” FF5, FF6; see also FF4 (teaching that “[g]rinding the submucosa in a frozen or freeze-dried state” is an advantageous way of comminuting the “submucosa starting material”). Thus, Hiles suggests a method wherein submucosa is pulverized (i.e., reduced to fine particles) in a frozen state, and further teaches that multiple iterations of comminution may be performed on its submucosa starting material. Accordingly, we agree with the Examiner that a skilled artisan would have found it obvious, based on the teaching in Hiles, to freeze donor tissue and pulverize the frozen tissue, prior to suspending the tissue and homogenizing the suspension, as recited in claim 1. Appeal 2020-003297 Application 15/444,445 15 provide the product to be used in repairing the lesion or defect.” Appeal Br. 27. The Examiner asserts Example 11 teaches that to produce a sponge, the comminuted SIS is hydrated (See Hiles et al, ¶0071), which reads on claimed step g) re-suspending the precipitated tissue particles, placed into a mold, and then vacuum-dried, which reads on claimed step h) lyophilizing the tissue resuspension. Ans. 21. However, while we agree that Hiles teaches using comminuted hydrated SIS in Example 11, FF9, Hiles also teaches that the comminuted SIS was centrifuged and the supernatant poured off before the remaining “dough-like” SIS is poured into molds and vacuum-dried. FF8. The Examiner has not persuasively explained why the comminuted SIS, after being centrifuged and with the supernatant removed, would still read on a suspension. Accordingly, we reverse the Examiner’s rejection of claim 1 as obvious over Hiles. We reverse the rejection of claims 2–12, which depend from claim 1, for the same reason. In re Fritch, 972 F.2d 1260, 1266 (Fed. Cir. 1992) (explaining that “dependent claims are nonobvious if the independent claims from which they depend are nonobvious”). Claim 14 recites “[a] method for repairing a lesion or defect at a tissue site in a human or animal patient body, the method comprising” the steps of claim 1 and the additional steps of “reconstituting the dry formulation [resulting from lyophilizing the tissue re-suspension] to form a slurry” and “implanting the slurry into the lesion or defect at the tissue site in the human or animal patient body.” Appeal Br. 35 (Claims App.). We therefore reverse the Examiner’s rejection of claim 14 as obvious over Hiles for the Appeal 2020-003297 Application 15/444,445 16 same reason discussed above. We likewise reverse the rejection of claims 15–19, which depend from claim 14. In re Fritch, 972 F.2d at 1266. b) Claims 13, 20 As the Examiner points out, claims 13 and 20 are product-by-process claims or product claims comprising product-by-process limitations. Ans. 5, 6–7. The Examiner considered these product-by-process limitations “only insofar as the method of production imparts distinct structural or chemical characteristics or properties to the product.” Id. The Examiner determines that, as for claim 13, such characteristics or properties include: human or animal tissue particles being of a size smaller than the starting tissue (given the tissue is pulverized); . . . contain a plurality of tissue particles (i.e. it cannot be a single tissue particle); . . . lyophilized; . . . physically capable of being placed at a lesion or defect site in a human or animal patient body; and upon placement at the lesion or defect site, . . . not detrimental to the human or animal patient body. Id. at 6. As for claim 20, the Examiner interprets the claim as being directed to “a product which comprises a matrix of a substantially non-mineralized native soft tissue (which covers all tissue except bone and teeth).” Ans. 7. The Examiner further concludes that the matrix must be a unitary structure (it cannot be a loose powder), and must be capable of containing or embedding other substances, such as cells; however, no cells are required (nor excluded). The matrix must also include a plurality of pores, it must also be lyophilized. From the product-by-process limitations, the matrix must also be formed of a plurality of pulverized particles, it cannot be a single particle of naturally occur[r]ing tissue. Id. Appeal 2020-003297 Application 15/444,445 17 With regard to the obviousness rejection of claims 13 and 20 over Hiles, the Examiner states as an initial matter that, “[f]ollowing the discussion of claim 1, . . . the sponges created by the method of Hiles . . . will necessarily meet the structural limitations of claims 13 and 20 by virtue of being made by the same method.” Ans. 13. The Examiner further determines that “[u]ltimately the products of claims 13 and 20 are considered obvious over the sponge disclosed in Example 11 of Hiles,” and “Appellants have not persuasively pointed out structural differences between the products of claims 13 and 20 and the sponge of Hiles.” Id. at 22. As discussed above, we find the Examiner has not established a prima facie case that Hiles renders obvious the method of claim 1. Nevertheless, we determine that the Examiner has established a prima facie case that the products of claims 13 and 20 are obvious over the product of Hiles and that Appellant has not produced evidence showing, or persuasively argued, that the Examiner’s determinations with respect to these product-by-process claims are incorrect. Only those arguments made by Appellant in the Briefs have been considered in this Decision. Arguments not presented in the Briefs are waived. See 37 C.F.R. § 41.37(c)(1)(iv). Appellant contends that “the method of Hiles is not the same method recited in Independent claims 1 and 20” and that, thus, “there is no foundation for the rejection of claims 13 and 20 as obvious in view of Hiles.” Appeal Br. 30. While we agree that the Examiner has not established that the method of Hiles is identical to the method of claim 1 or includes all of the process limitations of claim 20, this does not end the inquiry, because “[t]he patentability of a product does not depend on its method of production. If the product in a product-by-process claim is the Appeal 2020-003297 Application 15/444,445 18 same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” In re Thorpe, 777 F.2d 695, 697 (Fed. Cir. 1985). Moreover, the predecessor of our reviewing court has explained that the “Patent Office bears a lesser burden of proof in making out a [prima facie] case . . . for product-by-process claims because of their peculiar nature,” In re Fessmann, 489 F.2d 742, 744 (CCPA 1974). We determine that the Examiner has met this burden by explaining how the sponge in Example 11 of Hiles meets the respective structural limitations in claims 13 and 20 outlined in the Answer and recited in this decision. This is particularly the case given that claim 13 itself recites no express structural limitations at all — although claim 1 implies certain structural limitations such as the inclusion of lyophilized tissue particles — and claim 20 recites only the express structural limitations of “a matrix of a substantially non- mineralized native soft tissue of the human or animal body . . . including a plurality of pores.” In this regard, we note that, while the Examiner has not shown how Hiles teaches step (h) of claim 1 (i.e., lyophilizing a re-suspension of precipitated tissue particles), Hiles teaches preparing a lyophilized small intestine submucosa sponge by taking comminuted SIS, centrifuging it, removing the supernatant, pouring the remaining dough-like SIS into various molds, and freezing and lyophilizing the material. FF8. Appellant has not provided any persuasive evidence that the product prepared according to Appellant’s claim 1 that includes a step of re-suspending precipitated tissue particles and then lyophilizing the re-suspension is structurally different Appeal 2020-003297 Application 15/444,445 19 from the lyophilized small intestine submucosa sponge prepared as disclosed in Hiles. Appellant contends that the Examiner’s interpretation of claim 13 ignores the statement of Dr. Estes in the Estes Declaration describing the nature of the product resulting from the method of claim 1. As specifically stated by Dr. Estes, “Unexpectedly, after using a tissue homogenizer to homogenize non-mineralized soft tissue, lyophilizing the re-suspension did not generate a loose powder. We expected to produce a powder, but instead got a solid, unitary structure.” Estes Declaration, Para. 21. The Examiner has selected product characteristics that are deliberately at odds with the statement of Dr. Estes, who actually prepared the product according to the method steps of claim 1. Appeal Br. 13. We are not persuaded. As an initial matter, although Dr. Estes states that he “prepared a composition according to the claims of the current application,” it is unclear exactly how each step was performed. Neither does Dr. Estes explain how he comminuted the tissue in attempting to create the product of Hiles’ Example 11, other than that he collected particles that were in the 150 µm range. Estes Decl. ¶¶ 8, 14. In response to similar points made by the Examiner (Non-Final Act. 7; Ans. 17), Appellant contends that, unless the Examiner is questioning the veracity of Dr. Estes assertion that he “prepared a composition according to the claims of the current application”, that statement must be accepted as fact; and if that statement is fact, then all of the method steps recited in claim 1 were performed by Dr. Estes to produce the results set forth in the Estes Declaration. Reply Br. 9; see also Appeal Br. 14–15. Appellant also contends that “Hiles does not indicate how the comminuted SIS is obtained in Example 11, suggesting that whether the tissue is comminuted by ‘tearing, cutting, Appeal 2020-003297 Application 15/444,445 20 grinding, shearing or the like’ set forth in ¶[0046] is not relevant, provided the particle size is approximately 150 µm as in Example 11.” Appeal Br. 18. Appellant further contends that “[t]he Examiner . . . has not set forth any foundation for the criticality of how the SIS is comminuted.” Id. We are not persuaded. Contrary to Appellant’s reasoning, [t]he Board has broad discretion as to the weight to give to declarations offered in the course of prosecution. See Velander v. Garner, 348 F.3d 1359, 1371 (Fed. Cir. 2003) (“[A]ccord[ing] little weight to broad conclusory statements [in expert testimony before the Board] that it determined were unsupported by corroborating references [was] within the discretion of the trier of fact to give each item of evidence such weight as it feels appropriate.”). In re Am. Acad. of Science Tech Ctr., 367 F.3d at 1368 (alterations in original). Furthermore, “It is well established that the objective evidence of nonobviousness must be commensurate in scope with the claims.” In re Lindner, 457 F.2d 506, 508 (CCPA 1972). Thus, where declaration testimony is conclusory or otherwise not commensurate in scope with the claims, we have broad discretion as to the weight to give to that testimony. To the best of our understanding, it appears that Dr. Estes used a rotor-stator tissue homogenizer to both break down the tissue initially provided into the homogenizer into smaller particles and to mix those tissue particles in the suspending fluid to “prepare[] a composition according to the claims of the current application.” Estes Decl. ¶¶ 14, 17–21. As an initial matter, we note that the Estes Declaration is unclear as to whether the tissue homogenizer used in fact homogenizes the tissue suspension. Dr. Estes states, for example, that “[n]o matter what speeds or volumes of suspensions, [the inventors] could not make a homogeneous suspension containing only small particles of the cartilage” and that, Appeal 2020-003297 Application 15/444,445 21 “[w]hile many of the particles were sheared and broken down by the homogenizer, many more of the particles were not being broken down in the process.” Estes Decl. ¶ 19. Dr. Estes does not explain whether the inventors were eventually able to make a homogeneous suspension, saying only that, “[i]nstead, unexpectedly, during processing of the tissues[] the tissue homogenizer was also acting as a high speed blender or mixer, intertwining the tissue fragments and collagenous matrices together.” Id. ¶ 20. We note that Appellant urges in the claim construction of tissue homogenizer that homogenizing is the dispersion of similarly sized fragments evenly throughout a mixture. Appeal Br. 8. However, Appellant also appears to suggest that claim 1 does not require all of the tissue suspension to be homogenized. Appeal Br. 9 (stating that “simply because all of the tissue was not sheared and broken down does not mean that the tissue homogenizer did not create the product described by Dr. Estes that results from performing the steps of Applicant’s claim 1” and that, “[t]o the contrary, the product that had ‘incomplete’ processing of some tissue particles is the very product that resulted from the process and . . . exhibited the surprising characteristics identified by Dr. Estes that distinguishes this product from all of the prior art cited by the Examiner”). We note that such a construction improperly reads out the limitation of “homogenizing the tissue suspension using a tissue homogenizer.” (Emphasis added.) Thus, Dr. Estes’ declaration evidence does not establish that the product he made is one that is made according to all of the requirements of claim 1. It further appears that the alleged unexpected structural properties of the product result specifically from the use of the particular type of tissue homogenizer (i.e., a rotor-stator tissue homogenizer) to both pulverize and Appeal 2020-003297 Application 15/444,445 22 mix the variously sized particles of tissue in the suspension. Estes Decl. ¶¶ 14, 17–21. The claim, however, neither requires the use of a particular kind of tissue homogenizer to homogenize the tissue suspension, nor requires the use of any tissue homogenizer to pulverize the frozen tissue. Thus, to the extent the Estes Declaration suggests that the products made using the specific tissue homogenizer that is not required by Appellant’s claim may have different structural characteristics from the sponge of Hiles’ Example 11, the evidence is not persuasive that the sponge of Hiles’ Example 11 does not have structure identical to the products required by claims 13 and 20. Similarly, as the Examiner points out and Appellant has not disputed, the Estes Declaration appears to only address a method using cartilage, whereas claim 13 encompasses any human or animal tissue. Non-Final Act. 6; Appeal Br. 14. Thus, the Estes Declaration does not suggest that the sponge of Hiles’ Example 11 would not have structure identical to products encompassed by claim 13 and produced using non-cartilage tissues. Appellant contends that cartilage falls within the scope of claim 1 and all of the examples described in the original Specification refer to cartilage. Appeal Br. 14. Appellant contends that “[i]t is irrelevant to establishing the nature of the structural changes in the tissue whether that tissue is only cartilage, rather than every other possible type of tissue” and that “[t]he Examiner has . . . not provided any evidence that any other tissue obtained from a donor human or animal will not exhibit the same properties as described in the Estes Declaration.” Id. We are not persuaded because, once the Examiner has established a prima facie case with respect to the obviousness of claim 13, the burden shifts to Appellant to “demonstrate the Appeal 2020-003297 Application 15/444,445 23 unobvious character of his claimed invention over the cited references,” In re Fessmann, 489 F.2d at 745. As the Examiner explains, the evidence produced in the Estes Declaration, to the extent it relates only to cartilage, is not commensurate with the scope of the claims. Non-Final Act. 6. Accordingly, we are not persuaded that Dr. Estes’ declaration shows that the sponge of Hiles’ Example 11 is structurally different from the products required by claims 13 and 20, and we affirm the Examiner’s rejection of claims 13 and 20 as obvious over Hiles. C. Anticipation rejection over Hiles (claims 13, 20) 1. Issue The Examiner interprets claims 13 and 20 as product-by-process claims having the characteristics discussed above in connection with the obviousness rejection of claims 13 and 20 over Hiles. The Examiner finds that Hiles teaches “biomaterial comprising purified submucosal tissue treated so as to have shape memory and a shaped configuration” and that Example 11 of Hiles describes “a lyophilized sponge of small intestinal submucosa (SIS)” produced by lyophilizing, in pre- formed molds, a mixture having a “dough-like consistency” (i.e., slurry) of comminuted SIS having mean particles size 150 μm. Ans. 7. The Examiner finds that the lyophilized SIS sponge of Hiles meets all of the structural limitations of claim 13 recited above because (1) SIS is animal tissue; (2) the sponge is “comprised of a plurality of comminuted SIS particles, each particle being smaller than the native SIS tissue”; (3) the sponge is lyophilized; and (4) the sponge “can be placed in a tissue defect” to “help facilitate tissue repair.” Ans. 8. Appeal 2020-003297 Application 15/444,445 24 The Examiner similarly finds that the lyophilized SIS sponge of Hiles meets the structural limitations of claim 20 recited above. Ans. 8. The Examiner finds that SIS is non-mineralized animal tissue and that the sponge is a “unitary structure” comprising “a plurality of comminuted tissue particles.” Id. The Examiner finds that a “‘sponge’ structure will have a plurality of pores” and that the porous structure of Hiles’ sponge is further evidenced by Hiles’ teaching that “the sponge ‘provides three-dimensional structure for cell culture or in vivo growth.’” Id. at 7. Finally, as already discussed, the Examiner finds that Hiles’ sponge is lyophilized and “can be introduced into a tissue site in a human or animal body.” Id. at 8. Appellant contends that the rejection is improper as to claim 13 because the Examiner disregarded step (e) of claim 1, i.e., “homogenizing the tissue suspension using a tissue homogenizer” and “fail[ed] to consider the factual evidence provided in the Estes Declaration.” Appeal Br. 16–17, 20. Appellant contends that “the manner in which the starting material is homogenized imparts critical structural properties to the final product.” Id. at 19. Appellant contends that the rejection of claim 20 “suffers from the same errors . . . so . . . should be reversed for the same reasons.” Id. at 20. The issues with respect to this rejection are (1) whether the Examiner has provided a rationale tending to show that the claimed product appears to be the same or similar to the prior art product and, if so, (2) whether Appellant has provided evidence establishing differences between the claimed and prior art products. 2. Analysis Unless otherwise noted, we adopt the Examiner’s findings of fact and reasoning regarding the rejection of claims 13 and 20 as anticipated by Hiles Appeal 2020-003297 Application 15/444,445 25 (Final Act. 2–3, 4–10; Ans. 3–4, 5–8, 15–16, 17–19). We address Appellant’s arguments below. Only those arguments timely made by Appellant in the briefs have been considered; arguments not so presented in the briefs are waived. See 37 C.F.R. § 41.37(c)(1)(iv) (2015); see also Ex parte Borden, 93 USPQ2d 1473, 1474 (BPAI 2010) (informative) (“Any bases for asserting error, whether factual or legal, that are not raised in the principal brief are waived.”). Appellant contends that “[i]t is undeniable that Hiles does not disclose homogenizing with a tissue homogenizer” and that the Examiner’s rejection “eliminate[s] the homogenizing step (e) of parent claim 1.” Appeal Br. 17. Even assuming this to be true, we are not persuaded by such a statement standing alone, because, as discussed above, “[t]he patentability of a product does not depend on its method of production.” In re Thorpe, 777 F.2d at 697. In this case, we find that the Examiner has established a prima facie case that Hiles anticipates claim 13 by articulating why the sponge of Hiles’ Example 11 has the same structure as a product encompassed by claim 13. Thus, it is not relevant to the anticipation rejection that Hiles does not teach any particular step in Appellant’s product-by-process claims, unless Appellant provides evidence that the step imparts a structural difference to the product of claim 13 that is not present in Hiles’ prior art product. As already discussed above in the context of the obviousness rejection of claim 13 over Hiles, we are not persuaded that Appellant’s proffered evidence shows such a structural difference. Appellant contends that the Examiner’s improper and incorrect interpretation of “tissue homogenizer” recited in the homogenizing step (d) of claim 1 infects the interpretation of product-by-process claim 13. Again, Appeal 2020-003297 Application 15/444,445 26 the Examiner’s interpretation of “tissue homogenizer” is that it simply mixes or blends components without imparting any structural modification to the tissue being homogenized. . . . [T]his interpretation is at odds with the ordinary and customary meaning of this term to a person of ordinary skill in this art. Appeal Br. 13–14, 17 (contending that the Examiner’s rejection is based on the erroneous assertion that “homogenizing suspended tissue particle does not alter the tissue composition or produce any structural change in the tissue composition (not just the tissue particles), regardless of how the tissue composition is homogenized”). We are not persuaded for the reasons discussed above in the claim construction section of the opinion. Accordingly, we are not persuaded that the sponge of Hiles’ Example 11 would not have the same structure as a product encompassed by claims 13 and 20 merely because Hiles does not disclose homogenization via a “tissue homogenizer” as Appellant defines that term. Appellant contends that the Estes Declaration shows that “the resulting product [of Hiles’ Example 11] is ‘a powder conglomerate made up of non-unified particles,’” which is “very different [from] the product produced according to the present invention, which is an ‘interconnected unitary scaffold or matrix having entangled particulate fibers and an intertwined structure having a cotton candy-like appearance.’” Appeal Br. 17–18. We are not persuaded. As discussed above, the claims are not limited to products prepared using a “rotor-stator” tissue homogenizer, which the Estes Declaration states imparts specific structural characteristics to the tissue that was processed with the rotor-stator tissue homogenizer. Estes Decl. ¶¶ 16–21. Furthermore, as also discussed above, we find that Hiles Appeal 2020-003297 Application 15/444,445 27 teaches specific methods of comminuting the tela submucosa for purposes of preparing its product. FF4. Thus, the Estes Declaration, which does not describe how the SIS particles were comminuted in allegedly preparing a product according to the method described in Hiles’ Example 11, and which appears to have used only a rotor-stator tissue homogenizer in preparing a product according to the claims, does not persuaded us that the products produced by the processes recited in claims 13 and 20 are different than the product of Hiles’ Example 11.9 Appellant disputes the Examiner’s assertion that “the declaration is not commensurate in scope with the method/product of the instant claims” by pointing to its arguments above. Appeal Br. 18. We understand Appellant to be referring to its arguments that the declaration is commensurate with the scope of the claims because “tissue homogenizer” should be construed as Appellant proposes. We are not persuaded for the same reasons discussed above, namely that we agree with the Examiner that Appellant’s construction of “tissue homogenizer” is unduly narrow. Appellant also contends that “[t]here is no basis to conclude that how the starting material is comminuted to the requisite 150 µm is critical in any matter.” Appeal Br. 18. More particularly, Appellant contends that the comminuted SIS starting material in Example 11 of Hiles corresponds to steps (a)-(d) of parent claim 1. Thus, whether or not the comminuted SIS starting material of Hiles Example 11 is comminuted by a high-speed blender is irrelevant to the subsequent steps of Applicant’s invention. Second, as explained above, a high-speed blender is not a tissue homogenizer to a 9 In this regard, we also note that, in contrast to the description in Estes Declaration of “a powder conglomerate,” Estes Decl. ¶ 13, Hiles’ Example 11 teaches that its process produced a “sponge,” FF8. Appeal 2020-003297 Application 15/444,445 28 person of ordinary skill according to the only evidence of record - the Estes Declaration. Third, as noted above, Hiles does not describe a homogenization step in Example 11 that is distinct from the comminution step used to prepare the starting material. The Examiner cannot dismiss the comparative study undertaken by Dr. Estes by arbitrarily declaring that a data point not provided by Hiles (how the comminuted SIS of Example 11 is obtained) is a result-critical piece of information. Moreover, even considering how the initial comminuted SIS starting material is produced fails to consider that the homogenizing step of claim 1 is separate from and subsequent to a comminution step, such as the step used to prepare the comminuted SIS in Hiles Example 11. Id. at 19–20. We are not persuaded. We have explained why we agree with the Examiner’s construction of the term “tissue homogenizer.” Similarly, as we have explained above, for purposes of a product-by-process claim, it is the product, not the method of its production, that must be different from the prior art product. In re Thorpe, 777 F.2d at 697. In this case, the Examiner has pointed to Example 11 of Hiles, which teaches a lyophilized SIS sponge that appears to be “identical with or only slightly different than a product claimed” in Appellant’s product-by-process claims. In re Brown, 459 F.2d 531, 535 (CCPA 1972). Thus, the burden shifts to Appellant to come forward with evidence establishing a difference between the claimed product and the prior art product. In re Marosi, 710 F.2d 799, 803 (Fed. Cir. 1983). Appellant has not produced persuasive evidence to meet this burden. Appellant also contends that “Hiles[’] only mention of homogeneity concerns the use of protease digestion of tela submucosa ‘to solubilize the tissue and form substantially homogeneous solution’” and that, even if “Hiles does disclose using a blender and dewatering to produce a powder,” Appeal 2020-003297 Application 15/444,445 29 “the method for producing the product of Hiles Example 11 does not refer to homogenizing or the use of the high-speed blender described in other excerpts.” Appeal Br. 17. We are not persuaded. Hiles’ Example 11 teaches using comminuted SIS to prepare a lyophilized sponge. FF8. Hiles also teaches producing solutions or suspensions of SIS by “comminuting and/or digesting the tela submucosa with a protease . . . , for a period of time sufficient to solubilize the tissue and form substantially homogeneous solution.” FF4. Hiles further teaches comminuting the SIS by “tearing, cutting, grinding, shearing or the like,” especially “[g]rinding the submucosa in a frozen or freeze-dried state” or “subjecting a suspension of pieces of the submucosa to treatment in a high speed blender and dewatering, if necessary, by centrifuging and decanting excess waste.” FF4. Thus, these disclosures are directly related to each other by Hiles’ teachings. Accordingly, for the reasons discussed above, we affirm the Examiner’s rejection of claim 13 as anticipated by Hiles. Appellant does not separately argue claim 20, which falls with claim 13. D. Anticipation rejection over Gertzman (claim 13) 1. Issue Gertzman’s Example 1 teaches “[a] malleable putty of hyaluronic acid 4% with 100-800 micron sized demineralized cortical allograft bone powder having a residual calcium weight of 0.95% constituting approximately @ 32% total weight percentage of the composition.” Gertzman ¶ 71. Gertzman further teaches that Appeal 2020-003297 Application 15/444,445 30 [t]he example was formulated with 66 grams of freeze dried demineralized cortical allograft bone of particle size of 100-800 microns mixed into 140.3 grams of a 4% solution of hyaluronic acid (mol. wt, approximately 700,000 Daltons) in phosphate buffered saline. The bone component is added to achieve a bone concentration of approximately 32% (w/w). The solution is well mixed and allowed to stand for 2-3 hours at room temperature. This provides a malleable putty with a penetration unit of 61 and excellent formability properties and a pH of 7.2. Id. ¶ 72. The Examiner finds that Gertzman teaches the application of the malleable putty to a bone defect site and further finds that the bone powder used to create the putty reads on instant claim 13 as construed above. Ans. 8–9. Appellant contends that the rejection is based on an “improper interpretation of claim 13 as only requiring a loose powder.” Appeal Br. 22. Appellant further contends that “Gertzman does not disclose a product that results from homogenizing a tissue suspension using a tissue homogenizer.” Id. Appellant contends that “[t]he Examiner has not suggested, nor is it possible, that the product disclosed in Gertzman, achieves the product of the present invention ‘having entangled particulate fibers and an intertwined structure.’” Id. The issue with respect to this rejection is whether a preponderance of the evidence of record supports the Examiner’s finding that the bone powder disclosed in Gertzman’s Example 1 reads on the product recited in claim 13. 2. Findings of Fact 10. Gertzman teaches a malleable bone putty and a flowable pastel composition for application to a bone defect site to promote new bone growth at the site which comprises a new bone growth inducing compound Appeal 2020-003297 Application 15/444,445 31 of partially demineralized lyophilized allograft bone material having a residual calcium content ranging from 4 to 8% dry weight. Gertzman Abstract. 11. Gertzman teaches that the bone powders used in its composition “has a particle size ranging from about 100 to about 800 microns.” Gertzman Abstract. 12. Gertzman teaches an example of “[a] malleable putty of hyaluronic acid 4% with 100-800 micron sized demineralized cortical allograft bone powder having a residual calcium weight of 0.95% constituting approximately @ 32% total weight percentage of the composition.” Gertzman ¶ 71 (Example 1). 13. Gertzman teaches that Example 1 “was formulated with 66 grams of freeze dried demineralized cortical allograft bone of particle size of 100-800 microns mixed into 140.3 grams of a 4% solution of hyaluronic acid (mol. wt, approximately 700,000 Daltons) in phosphate buffered saline.” Gertzman ¶ 72. 14. Gertzman teaches that, in the preferred embodiment, [t]he bone segments are milled and placed in a sieve to size the milled bone to 100-800 microns or coarse ground to achieve cortical/cancellous chips in the form of irregularly shaped polyhedra with an edge dimension up to 5 mm. The milled bone material is placed in mixing container and cleaned with a 5:1 ratio of 3% Hydrogen Peroxide and stirred for 15 minutes, removed and rinsed with a minimum of 3000 ml of sterile water. The rinsed bone powder is placed back into the cleaned mixing container and at least 1000 ml of 70% sterile ethanol is added and the solution is mixed for 30 minutes. The bone powder is then transferred into a No. 70 sieve and an open vacuum is applied to the bottom of the sieve and the bone powder is dried for 20 minutes. The dried bone powder is transferred to the Appeal 2020-003297 Application 15/444,445 32 demineralization process where it is weighed. The bone weight in grams is compared to a chart which determines the acid volume to be applied which is approximately 1 gram equals approximately 16 ml of acid. The bone powder is mixed with 0.6N HCl for about 2½ hours to achieve maximum bone powder surface engagement with the HCl to remove most of the mineral content. Gertzman ¶ 42. Gertzman teaches a slightly different demineralization process when cortical/cancellous bone chips are used. Id. ¶ 43 (treating bone chips with 0.6N HCl at a different ratio and/or for different length of time). Gertzman further teaches rinsing the bone material with water, adding buffer solution, then rinsing the buffered bone powder with sterile water. Id. ¶ 44. 15. Gertzman teaches that “[d]emineralized allograft bone is usually available in a lyophilized or freeze dried and sterile form to provide for extended shelf life.” Gertzman ¶ 11. 3. Analysis Unless otherwise noted, we adopt the Examiner’s findings of fact and reasoning regarding the rejection of claim 13 as anticipated by Gertzman (Final Act. 10–11; Ans. 8–9, 19). We address Appellant’s arguments below. Only those arguments timely made by Appellant in the briefs have been considered; arguments not so presented in the briefs are waived. See 37 C.F.R. § 41.37(c)(1)(iv); see also Ex parte Borden, 93 USPQ2d at 1474. Appellant contends that the rejection is based on an “improper interpretation of claim 13 as only requiring a loose powder.” Appeal Br. 22. Appellant contends “[a] loose powder with no structure or form is not capable of repairing a lesion or defect at a tissue site,” as required by the preamble of claim 1 to which claim 13 refers, “in part because there is Appeal 2020-003297 Application 15/444,445 33 nothing to hold the powder at the site.” Appeal Br. 5. We are not persuaded because, as discussed above, the claims do not preclude use of devices (e.g., bandages) that would retain a loose powder at a tissue site so as to allow it to repair a lesion or defect at a tissue site. Appellant further contends that “Gertzman does not disclose a product that results from homogenizing a tissue suspension using a tissue homogenizer.” Appeal Br. 22. Appellant contends that, “[n]otably, Gertzman makes no mention of homogenization in any respect” and that, “[i]nstead, in Example I relied on by the Examiner, the freeze-d[r]ied [demineralized bone matrix (DBM)] is ‘mixed into’ a solution of hyaluronic acid, and ‘well mixed and allowed to stand for 2-3 hours at room temperature.’” Id. We are not persuaded. Claim 13 recites a product produced according to the method of claim 1, which includes a step of homogenizing a suspension of pulverized tissue using a tissue homogenizer. However, as discussed above, “[t]he patentability of a product does not depend on its method of production.” In re Thorpe, 777 F.2d at 697. Instead, “[i]f the product in a product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process.” Id. In this case, after the homogenizing step, claim 1 recites precipitating the particles from the homogenized suspension and re-suspending the precipitated tissue particles without further homogenizing the re-suspension. For reasons similar to those discussed above with respect to the rejection over Hiles and reiterated below, we are not persuaded by Appellant’s argument that a re-suspension of particles precipitated from a homogenized Appeal 2020-003297 Application 15/444,445 34 suspension of tissue pulverized using a tissue homogenizer, which is then lyophilized, would result in a product having a different structure than the demineralized bone powder of Gertzman. Appellant contends that “[t]he Examiner has not suggested, nor is it possible, that the product disclosed in Gertzman, achieves the product of the present invention ‘having entangled particulate fibers and an intertwined structure.’” Appeal Br. 22. We are not persuaded because Appellant relies on the Estes Declaration as evidence that the claimed product will have entangled particulate fibers and an intertwined structure, and, as discussed above, the Estes Declaration at most suggests that homogenizing the tissue using a particular type of tissue homogenizer (i.e., a rotor stator) would result in products having entangled particulate fibers and an intertwined structure. Claim 1, however, is not limited as to the particular type of rotor stator used. Accordingly, we affirm the Examiner’s rejection of claim 13 as anticipated by Gertzman. E. Anticipation rejection over Lin (claim 13) 1. Issue The Examiner finds that Lin teaches “compositions for delivering osteotherapeutic materials . . . containing demineralized bone matrix (DBM)” and “methods of applying the compositions to defective bone tissue and/or other viable tissue to promote formation of new bone.” Ans. 9. The Examiner finds that, “[i]n Example 16 Lin . . . teach[es] forming a DBM/Bone-chip/Hydrogel matrix by mixing DBM[] having particle size of <0.5 mm, bone chips and macromers into a solution,” pouring the resulting Appeal 2020-003297 Application 15/444,445 35 “thick slurry” into a mold and freezing, lyophilizing, and crosslinking it to form “a cohesive flexible matrix.” Id. The Examiner finds that “[t]he DBM/Bone-chip/hydrogel matrix of Example 16 of Lin” reads on claim 13 because it is “from animal tissue (bone, . . . comprised of a plurality of particles, each particle being smaller than the native bone tissue, and is lyophilized.” Id. Appellant contends that “[t]his rejection is improper for the same reasons as the other improper prior art rejections of claim 13 and because the Examiner’s interpretation of claim 13 is improper.” Appeal Br. 22. In particular, Appellant contends that “Lin makes no mention of homogenization in any respect” and that, because the matrix of Lin results from the cross-linking or polymerization of the constituents rather than the DMB/bone-chip component, “there is no need for a homogenization step as recited in [Appellant’s] claims.” Id. at 22–23. The issue with respect to this rejection is whether a preponderance of the evidence of record supports the Examiner’s finding that the bone powder disclosed in Lin’s Example 16 reads on the product recited in claim 13. 2. Findings of Fact 16. Lin teaches that demineralized bone matrix (DBM) is “the protein component of bone,” “prepared from donated bone tissue by first grinding the cortical bone to desired particle size, then removing minerals from the bone particles in hydrochloric acid, and finally lyophilizing demineralized particles to eliminate water.” Lin ¶ 18. 17. Lin teaches that [d]emineralized allograft bone powder is typically available in a lyophilized or freeze dried and sterile form to provide for extended shelf life. The demineralized bone component of the Appeal 2020-003297 Application 15/444,445 36 composition herein is a known type of pulverized or powdered material and is prepared in accordance with known procedures. It should be understood that the term “demineralized bone matrix” includes bone particles of a wide range of average particle size ranging from relatively fine powders to coarse grains and even larger chips. So, for example (which example is intended to be illustrative and not restrictive), the bone powder present in the composition of this invention may range in average particle size from about 100 to about 1,200 μm or from about 125 to 850 μm. Id. ¶ 20. 18. Example 16 of Lin teaches: Other manners of polymerization may be used for grafts containing DBM. For example (which example is intended to be illustrative and not restrictive), polymerization may be initiated by thermal initiation. A 0.700 g solution of macromer with 0.147 g solids, containing 5.88 mg of benzoyl peroxide, was prepared. Then 0.1039 g (10.4% by weight) of bone chips with a particle size of >0.5-<1.18 mm, and 0.1959 g (19.6% by weight) of DBM (demineralized bone material) with a particle size of <0.5 mm was incorporated into the solution. The resulting thick slurry was shaped into a 12 mmx2.5 mm disc, frozen and lyophilized. Once lyophilized, crosslinking of macromer in the shaped disks was initiated at 50° C. over a 10-hour time period under vacuum. The resulting material had formed a single, cohesive flexible matrix. The matrix was able to be rehydrated in water and was easily manipulated without fragmenting or disrupting. Re-drying and rewetting of the DBM/Bone-chip/Hydrogel matrix at room temperature was feasible. Lin ¶ 150. 3. Analysis Unless otherwise noted, we adopt the Examiner’s findings of fact and reasoning regarding the rejection of claim 13 as anticipated by Lin (Final Act. 11–12; Ans. 9, 19–20). We address Appellant’s arguments below. Only those arguments timely made by Appellant in the briefs have been Appeal 2020-003297 Application 15/444,445 37 considered; arguments not so presented in the briefs are waived. See 37 C.F.R. § 41.37(c)(1)(iv); see also Ex parte Borden, 93 USPQ2d at 1474. Appellant contends that the rejection of claim 13 over Lin “is improper for the same reasons as the other improper prior art rejections of claim 13 and because the Examiner’s interpretation of claim 13 is improper.” Appeal Br. 22. We are not persuaded for the reasons already discussed above. Appellant contends that “Lin makes no mention of homogenization in any respect.” Appeal Br. 22. Appellant contends that, because “[t]he matrix of Lin is not due to the [DBM]/bone chip component,” “there is no need for a homogenization step as recited in Applicant’s claims,” and “the DBM/Bone chip/hydrogel matrix in Example 16 of Lin does not meet the limitations of Applicant’s claim 13 and parent claim 1.” Id. at 23. We are not persuaded because, as discussed above, the patentability of a product-by-process claim does not depend on the process by which the product is made. Appellant has not provided persuasive evidence that a product prepared by precipitating tissue particles from a homogenized suspension and then re-suspending the precipitated particles (without further homogenizing the re-suspension) would result in a product that is structurally different from a product that is not homogenized in the first instance. Accordingly, for the reasons discussed above, we affirm the Examiner’s rejection of claim 13 as anticipated by Lin. Appellant does not separately argue claim 20, which falls with claim 13. CONCLUSION Appeal 2020-003297 Application 15/444,445 38 In summary: Claim(s) Rejected 35 U.S.C. § Reference(s)/Basis Affirmed Reversed 1–20 103(a) Hiles 13, 20 1–12, 14–19 13, 20 102(b) Hiles 13, 20 13 102(a), 102(e) Gertzman 13 13 102(a), 102(e) Lin 13 Overall Outcome 13, 20 1–12, 14–19 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). See 37 C.F.R. § 1.136(a)(1)(iv). AFFIRMED IN PART Copy with citationCopy as parenthetical citation