DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Applicants’ response of 6/3/2026 has been received and entered into the application file.
Priority
Applicants submitted a petition for modified priority claim (petition to accept an unintentionally delayed priority claim) . The petition was GRANTED.
Acknowledgement is made of Applicants’ claim for benefit under 35 USC 120 as a continuation of prior-filed US application 15/444445 (filed 2/28/2017, now US Patent 11357889), which claims benefit under 35 USC 120 as a continuation of prior-filed US application 10/874402 (filed 6/23/2004, now abandoned).
The effective filing date for the instant claims is 6/23/2004.
Election/Restrictions
Applicants previously elected the species of claimed product comprising a suspension of morselized or pulverized cartilage, meniscus or IVD, and further comprising growth factors.
Claims 1-4, 6-14 read on the elected species and have been examined on the merits. Claims 5 and 15 have been withdrawn from consideration as being directed to non-elected species (there being no allowable generic or linking claim at this time).
Claim Interpretation
Claim 1 is directed to a product. The preamble states that the product is “for introduction within a soft tissue site of the human body”. The preamble recites an intended use of the product. In this case, the preamble is considered only in so far as it limits the product as being physically capable of being placed in a soft tissue site of the human body. Any material that is sized/shaped in such a manner that could be placed at soft tissue site will meet this limitation. MPEP § 2111.02.
The product comprises a suspension. A suspension is being given its ordinary meaning in the art, which is “a heterogeneous mixture of a fluid that contains solid particles sufficiently large for sedimentation, wherein the particles do not dissolve.” (See Wikipedia “Suspension (chemistry)”).
The terms soft tissue (e.g. of the NSTM) as well as non-mineralized soft tissue is understood to refer to all tissues except teeth and bones (See ¶009 of specification).
The following interpretation has been edited based on Applicants’ remarks: Regarding the term native soft tissue matrix (NSTM): Applicants have asserted “NSTM” is a term coined in the instant application and is defined in the instant application as meaning a pulverized soft tissue in the form of morsels (See ¶007).
Thus, “NSTM” is not a “matrix”, per se (the term “matrix” in the current field (biology/tissue engineering) being “a surrounding substance within which something can be contained or embedded” (from The Farlex Partner Medical Dictionary: matrix: 3. “A surrounding substance within which something is contained or embedded, for example, the fatty tissue in which blood vessels or lymph nodes lie provides a matrix for those embedded”)). The NSTM is not a unitary structure, but rather a collection of particulate matter. Applicants highlight in their response that NSTM and a “matrix” (unitary structure) are distinct (Response at Pg 5).
Given that Applicants assert NSTM is defined as pulverized soft tissue in the form of morsels, the limitation at lines 2-3 stating “the NSTM consisting of a morselized or pulverized substantially non-mineralized native soft tissue of the human body” only further limits the NSTM as being from human tissue.
Status of Prior Rejections/Response to Arguments
RE: Rejection of claims 1-4 and 6-14 under 35 USC 112, second paragraph: Applicants’ arguments and statements on the record are effective to overcome the rejections under 35 USC 112(b). The rejection is withdrawn.
RE: Rejection of claims 1-4 and 6-14 under 35 USC 102(b) over Awad et al:
The correction to the priority claim chain is effective to Awad et al not available as prior art. The rejection is withdrawn.
RE: Rejection of claims 1, 2, 6-8 and 10-13 under 35 USC 103(a) over Badylak et al:
Applicants have traversed the rejection asserting that the “fluidized form of submucosa” of Badylak et al is not a suspension of insoluble submucosal tissue particulate, but rather the submucosal tissue is solubilized. In support, Applicants point to the fact that Badylak et al says the powdered submucosal tissue can optionally be subjected to protease digestion to form a homogeneous solution (Badylak et al, col. 3, ln 46-49; emphasis added).
This argument has been fully considered, but is not found persuasive. Badylak et al teaches the protease digestion is optional. Thus Badylak et al teach embodiments where the submucosal powder is not subject to protease digestion, and thus remains in insoluble form.
Applicants further traverse the rejection asserting that Badylak et al does not teach 10-20% w/v concentration, and there is insufficient basis to find this value obvious. Applicants again assert that Badylak et al does not teach the fluidized form can be a suspension of the submucosa in a fluid. Applicants further assert that because there is no foundation to determine what is “routine optimization”.
This argument has been fully considered, but is not found persuasive. As above, Badylak et al teach protease digestion to solubilize the powder is optional, so there are embodiments of the fluidized form where the powder is not solubilized (i.e. remains insoluble). Badylak et al clearly state the viscosity of the fluidized composition can be manipulated by controlling the concentration of the submucosa component and the degree of hydration (See Badylak et al, col. 3, ln 67-col. 4, ln 2). This is considered a clear teaching that the concentration of the submucosal component is a result effective variable: directly effecting the final viscosity. Generally differences in concentration are not considered patentable, absent evidence of criticality. No evidence of criticality of the claimed range is present in the current prosecution file.
The rejection is maintained.
RE: Rejection of claims 1-4 and 6-14 under 35 USC 103(a) over Gomes et al: Applicants assert that Gomes et al teaches gels. Applicants assert the gel of Gomes is not a suspension.
The argument has been fully considered, but is not found persuasive. Gomes et al provide the same material, cartilage NSTM, in the same biological carriers (hyaluronic acid, gelatin, collagen, or buffered PBS) at generally the same concentrations as currently claimed. The gel of Gomes et al thus has the same composition as the currently claimed product and is appropriately considered to read on the claimed composition, and can be considered a suspension. Particularly when no crosslinking or gelling agent is provided (e.g. when the biocompatible fluid is buffered PBS), the combination of the cartilage powder and biocompatible fluid will create a suspension.
The rejection is maintained.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1, 2, 6-8, and 10-13 stand rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Badylak et al (US Patent 5695998).
Badylak et al disclose use of vertebrate submucosa-derived matrices as substrates for growth and attachment of cells (See col 1, ln 41-43). Small intestinal submucosa (SIS) is preferred (See col. 2, ln 76-col. 3, ln 2).
The submucosa can be in fluidized form. The fluidized submucosa can be formed by grinding frozen or freeze-dried submucosa tissue to form a powder, which can then be hydrated with water or a buffered saline to form a submucosal fluid of, inter alia, fluid consistency (See col. 3, ln 45-59). The viscosity of the fluidized submucosa can be manipulated by controlling the concentration of the submucosa component and the degree of hydration. Viscosities ranging from about 2 to about 300,000 cps (at room temperature) are disclosed (See col. 3, ln 66- col. 4, ln 5).
Badylak et al teach the compositions comprising submucosa, including the fluidized form, can be implanted into a host to regenerate tissue (See col. 6, ln 17-25). The compositions comprising the submucosa can be seeded with cells prior to the implantation The cells can be, inter alia, mesenchymal cells (stem cells), endothelial cells, keratinocytes or islets (See col. 6, ln 27-46).
Regarding claim 1: The fluidized form of submucosa is comparable to the instant claimed product. Submucosa is a substantially non-mineralized native soft tissue. Badylak et al report grinding the frozen or freeze-dried submucosa to form a powder. The powdered submucosa reads on morselized or pulverized substantially non-mineralized native soft tissue. The powder is resuspended in water or buffered saline. Both water and buffered saline read on a volume of a biologically compatible fluid. Given the powdered submucosa is rehydrated fluidized submucosa, and given that powdered submucosa is not soluble, per se, the fluidized submucosa reads on a suspension. It is emphasized that Badylak et alt each an optional step of protease digestion to solubilize all or a major portion of the submucosal tissue components. The embodiment wherein the submucosa is not subject to protease digestion is relied upon. In the absence of protease digestion, the powdered submucosa remains insoluble and will be present as a suspension within the water or buffered saline.
The fluidized submucosa of Badylak et al differs from the instant claims in that Badylak et al does not disclose the concentration of the submucosa powder is 10-20% w/v. However, Badylak et al does teach that the concentration of the submucosa can be manipulated to achieve a desired viscosity. As such, the concentration of submucosa powder is considered a result effective variable, and as such, would have been routinely optimized by one having ordinary skill in the art to achieve a desired viscosity for downstream applications.
Regarding the limitation wherein the suspension is operable to promote cellular growth within and through the NSTM, Badylak et al teach that their compositions, including fluidized compositions, can be seeded with eukaryotic cells (See col. 6, ln 27-46). Given the fluidized composition is capable of supporting cells, and contains essentially the same components as the material currently claimed (particulated soft tissue suspended in a biocompatible liquid), there is reasonable basis to conclude that the fluidized submucosal composition of Badylak et al also has the property is operable to promote cellular growth within and through the [particulated submucosa]. When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01.
Regarding claim 2: Following the discussion of claim 1 above, the buffered saline reads on a saline solution. Both water and buffered saline read on pharmaceutical solutions.
Regarding claim 6: Claim 6 limits the NSTM by the intended application site. However, since no specific application site is claimed, any NSTM can be considered to meet the limitation of claim 6, as it necessarily matches a soft tissue site. In the instant case, the small intestinal submucosa of Badylak et al satisfies the claim limitation.
Regarding claim 7: Following the discussion of claim 1 above, Badylak et al does not specify that the submucosa can be obtained from multiple intestinal sites, but it would have been prima facie obvious to have pooled multiple intestines to increase the available submucosal tissue available. Intestines from different donor animals will read on a combination of soft tissues from multiple soft tissue sites.
Regarding claim 8: Following the discussion of claim 1 above, the powdered submucosa is derived from freeze-dried submucosa. Freeze-drying will serve to devitalize the submucosal tissue.
Regarding claims 10-12: Following the discussion of claim 1 above, the fluidized submucosa can be further seeded with cells. Badylak et al disclose mesenchymal stem cells (which read on multipotential stem cells), as well as endothelial cells, keratinocytes and islets (which read on differentiated, and phenotype-specific cells). Any cell will necessarily be at least one of autologous, allogeneic or xenogeneic to the submucosa.
Regarding claim 13: Following the discussion of claim 10 above, the cells also read on bioactive molecules.
Claims 1-4 and 6-14 stand rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Gomes et al (US PGPub 2004/0219182).
Gomes et al discloses a cartilage defect implant material in paste or gel form for repairing articular cartilage defects. The material comprises milled allograft cartilage pieces in a bioabsorbable carrier. Autologous chondrocytes and/or chondrogenic stimulating factors, such as TGF-beta, BMP2, BMP7, PDGF, IGF-1, FGF2 (i.e. bFGF), and VEGF can also be added (See ¶0019).
In Example 1, Gomes et al teach formation of a cartilage implant material. Minced, lyophilized cartilage pieces, ranging in size from 0.01 mm to 1 mm, are combined with a bioabsorbable carrier. The bioabsorbable carrier can be, inter alia, hyaluronic acid, gelatin, collagen, or buffered PBS. The putty or paste can comprise 25-50% wt cartilage pieces, and 75-50% wt bioabsorbable carrier. Gel formulations can comprise 15-30% wt cartilage and 85-70% wt bioabsorbable carrier (See ¶0038). It is noted Gomes et al defines gel as a “mixture of minced or milled pretreated allograft cartilage in a bio composite carrier having a viscosity which is less than and is less rigid than a mixture of minced or milled pretreated allograft cartilage in a biocompatible carrier referred to by the terms “putty” or “paste” and contains less cartilage by weight than putty or paste” (See ¶0033). Based on this definition of “gel”, the “gel” reads on a suspension.
Regarding claims 1 and 4: The cartilage gel is comparable to the claimed product. The milled cartilage pieces reads on NSTM consisting of morselized or pulverized substantially non-mineralized native soft tissue. The bioabsorbable carrier, specifically at least the hyaluronic acid, gelatin, collagen or buffered PBS, reads on a biologically compatible fluid. Combining milled cartilage pieces with hyaluronic acid, gelatin, collagen or buffered PBS will create a suspension.
The gel is disclosed as containing 15-30% wt cartilage. This range substantially over laps with the claimed range of 10-20% w/v. In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976). See MPEP 2144.05(I). Therefore, the cartilage gel of Gomes et al is considered to at least render obvious the physical suspension of the instant claims.
Regarding the limitation wherein the suspension is operable to promote cellular growth within and through the NSTM, Gomes et al teach that their compositions can be combined with chondrocytes (See, e.g. Example 2 at ¶0039). Given the gel formulation is capable of being seeded with cells, and contains essentially the same components as the material currently claimed (particulated cartilage suspended in a biocompatible liquid), there is reasonable basis to conclude that the cartilage gel composition of Gomes et al also has the property is operable to promote cellular growth within and through the [particulated cartilage]. When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not." In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). See MPEP 2112.01.
Regarding claim 2: Following the discussion of claim 1 above, the buffered PBS reads on a saline solution, as well as a pharmaceutical solution.
Regarding claim 3: Following the discussion of claim 1 above, the gelatin, collagen, and hyaluronic acid all meet the claim limitations.
Regarding claim 6: Claim 6 limits the NSTM by the intended application site. However, since no specific application site is claimed, any NSTM can be considered to meet the limitation of claim 6, as it necessarily matches a soft tissue site. In the instant case, the cartilage of Gomes et al satisfies the claim limitation.
Regarding claim 7: Following the discussion of claim 1 above, Gomes et al does not specify that the cartilage can be obtained from allogenic donor sites, but it would have been prima facie obvious to obtained donor allograft cartilage from multiple cartilage sites within the donor body to maximize the available cartilage available. This is considered optimization of available materials and is thus prima facie obvious.
Regarding claim 8: Gomes et al discloses preparation of the donor cartilage material involves freezing to -70oC and lyophilization, both of which will devitalize the cartilage (See ¶0035).
Regarding claim 9: Following the discussion of claim 1 above, Gomes et al teaches milling the cartilage to 0.01 mm to 1 mm (10 µm to 1000 µm). This size range overlaps with the claimed size range. As above, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. As such, the claimed range is considered prima facie obvious.
Regarding claims 10-12: Following the discussion of claim 1 above, Gomes et al teaches autologous chondrocytes can be combined with the cartilage implant material. The chondrocytes are autologous to the intended recipient, but would be allogenic with respect to the cartilage pieces (noting allogenic cartilage is used).
Regarding claims 13-14: Following the discussion of claim 1 above, Gomes et al teaches chondrogenic stimulating factors, including TGF-beta, IGF, bFGF, PDGF, VEGF and BMPs can be included.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALLISON M FOX whose telephone number is (571)272-2936. The examiner can normally be reached M-F 10-6 EST.
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/ALLISON M FOX/Primary Examiner, Art Unit 1633
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