DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Priority
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).
Acknowledgement is further made of Applicants claim for benefit under 35 USC 120 as a continuation of prior-filed US application 10/874402 (filed 6/23/2004, now abandoned).
Applicant has not complied with one or more conditions for receiving the benefit of the earlier filing date of US Application 10/874492 under 35 U.S.C. 120 as follows:
This application is claiming the benefit of prior-filed application No. 10/874402 under 35 U.S.C. 120. Copendency between the current application and the prior application is required. Since the applications were never copending, the benefit claim to the prior-filed ‘402 application is improper. Applicant is required to delete the claim to the benefit of the prior-filed application, unless applicant can establish copendency between the applications.
The effective filing date for the instant claims is thus 2/28/2017, the filling date of the 15/444445 application.
Election/Restrictions
Applicant’s election without traverse of the species of claimed product comprising a suspension of morselized or pulverized cartilage, meniscus or IVD, suspended in a volume of biologically compatible fluid comprising synovial fluid, blood serum, blood plasma, or serum, and further comprising growth factors, in the reply filed on 10/23/2025 is acknowledged.
Upon reconsideration, the requirement to define the biologically compatible fluid is withdrawn.
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 Claims 5 and 15 have been withdrawn from consideration as being directed to non-elected species (there being no allowable generic or linking claim at this time).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).
Regarding the term native soft tissue matrix (NSTM): The broadest reasonable interpretation of the term “matrix” in the current field (biology/tissue engineering) is “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”). Thus, the NSTM must be a unitary structure (it cannot be a loose powder), and must be capable of containing or embedding other substances, such as cells.
Regarding the term morselized or pulverized substantially non-mineralized native soft tissue of the human body: The broadest reasonable interpretation of this phrase is morsels or pulverized particles derived from substantially non-mineralized native soft tissue. Morselization and/or pulverization of NSTM will yield morselized or pulverized substantially non-mineralized native soft tissue particles. The morselized or pulverized particles need not be a unitary structure (it can be a loose powder). The morselized or pulverized particles need not be capable of containing or embedding other substances, such as cells.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-4 and 6-14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claim 1: Claim 1 is to a product. The product comprises “a suspension of NSTM consisting of a morselized or pulverized substantially non-mineralized native soft tissue of the human body”. It is unclear if the transitional phrase “consisting of” is limiting the suspension, or the NSTM, per se. That is, it is unclear if the claim is meant to be read: (i) A product…. comprising a suspension of NSTM, said suspension consisting of a morselized or pulverized substantially non-mineralized native soft tissue of the human body and a volume of a biologically compatible fluid, said NSTM suspended in the [[a]] volume of a biologically compatible fluid such that the concentration of the NSTM is 10-20% w/v, wherein the…. or
(ii) A product…comprising a suspension of NSTM, said NSTM consisting of a morselized or pulverized substantially non-mineralized native soft tissue of the human body, said NSTM suspended in a volume of a biologically compatible fluid such that the concentration of the NSTM is 10-20% w/v, wherein the …
For purposes of compact prosecution, the (ii) interpretation is being adopted for the remainder of examination. Correction is required.
Furthermore, in claim 1, when interpreting the claim as being directed to “A product…comprising a suspension of NSTM, said NSTM consisting of a morselized or pulverized substantially non-mineralized native soft tissue of the human body, said NSTM being suspended in a volume of biologically compatible fluid…” it is unclear whether the suspension comprises multiple matrices (i.e. native soft tissue matrices) or if the suspension comprises morselized or pulverized particles of substantially non-mineralized native soft tissue of the human body. The problem is based on the fact that a matrix (as in NSTM) is considered a unitary structure (not a loose powder or individual particles) capable of containing or embedding other substances, such as cells. NSTM can be morselized or pulverized to create morselized or pulverized particles of substantially non-mineralized native soft tissue. A matrix is not synonymous with a morsel or pulverized particle. The difference has been important during prosecution and claim construction of the prior-filed applications, and thus is relevant to claim construction in the instant case. Thus, in order to determine claim scope, it is necessary to know if the claimed product comprises matrices (unitary structures) in suspension, or if the claimed product merely comprises morsels or particles in suspension. The metes and bounds of the claim cannot be determined.
Dependent claims 2-4 and 6-14 inherit the deficiency and are rejected on the same basis.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
Claims 1-4, and 6-14 are rejected under pre-AIA 35 U.S.C. 102(b) as being anticipated by Awad et al (US 2005/0288796).
Noting the effective filing date of the instant claims is 2/28/2017, the Awad et al PGPub is available as 102(b) art.
Regarding claims 1, 2, 4, and 6-9: At Example 1 Awad et al teach a NSTM-CH preparation. The NSTM-CH dry formulation consists of morselized or pulverized cartilage (a substantially non-mineralized native soft tissue) (See ¶0047-0050). The cartilage is devitalized by plunging in liquid nitrogen. The particle size can be 1-100 µm.
At point of care, the dry formulation of NSTM-CH is reconstituted with saline or a pharmaceutical solution of chondro-inductive growth factors. Awad et al teach chondro-inductive growth factors include TGF-beta, IGF, bFGF and BMPs (See ¶0045). The dry formulation of NSTM-CH can be 20% (w/v) of the solution. The solution with 20% (w/v) NSTM-CH in saline anticipates the product of claims 1, 2, 4 and 5-9. The solution with 20% (w/v) NSTM-CH in pharmaceutical solution of chondro-inductive growth factors anticipates the product of claims 1, 2, 4, 6-9 and 13-14.
Regarding claims 1-4, 6-12: At Example 4, Awad et al teach combining the NSTM-CH (of Example 1) with chondrocytes and synovial fluid (which contains proteoglycans and hyaluronic acid), such that the concentration of NSTM-CH is 10-20% (w/v) (See ¶0054-0055). The injectable suspension anticipates the product of claims 1-4 and 6-12.
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 are 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.
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 are 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 biocomposite 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). They do not define gel as meaning a ‘colloid’. Based on this definition of “gel”, the “gel” can read 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
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