DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/29/2025 has been entered.
Claims 1, 10, 12, and 15 have been amended. Claims 6 and 11 have ben newly canceled and no claims have been newly added.
Claims 1-3, 8-10, 12, 14-17 and 19-20 are currently pending.
Claims 10 and 12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/08/2023.
Claims 1-3, 8-9, 14-17 and 19-20 have been examined on their merits.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn due to amendments. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Claim Interpretation
Claim 1 is a product-by-process claim; claims 2-3, 8-9, 14-17, and 19-20 depend from said claim. M.P.E.P. § 2113 reads, “Product-by-process claims are not limited to the manipulations of the recited steps, only the structure implied by the steps.”
“Even though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the 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.” In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985) (citations omitted).
The structure implied by the process steps should be considered when assessing the patentability of product-by-process claims over the prior art, especially where the product can only be defined by the process steps by which the product is made, or where the manufacturing process steps would be expected to impart distinctive structural characteristics to the final product. See, e.g., In re Garnero, 412 F.2d 276, 279, 162 USPQ 221, 223 (CCPA 1979)
The use of 35 U.S.C. §§ 102 and 103 rejections for product-by-process claims has been approved by the courts. “[T]he lack of physical description in a product-by-process claim makes determination of the patentability of the claim more difficult, since in spite of the fact that the claim may recite only process limitations, it is the patentability of the product claimed and not of the recited process steps which must be established. We are therefore of the opinion that when the prior art discloses a product which reasonably appears to be either identical with or only slightly different than a product claimed in a product-by-process claim, a rejection based alternatively on either section 102 or section 103 of the statute is eminently fair and acceptable. As a practical matter, the Patent Office is not equipped to manufacture products by the myriad of processes put before it and then obtain prior art products and make physical comparisons therewith.” In re Brown, 459 F.2d 531, 535, 173 USPQ 685, 688 (CCPA 1972).
The limitations recited in the claims appear to relate to the properties of the fragmented collagen component after its treatment with an ultrasonic homogenizer and freeze-drying according to Applicant’s Specification pages 43-45 para 110-113. It is unclear how this process of preparation ultimately affects the structure of the final collagen component and the extracellular matrix-containing composition as a whole. Baring evidence to the contrary, any collagen component that is fragmented by ultrasonic fragmentation/homogenization and produces the claimed fragment size are deemed to meet the claim limitations.
Applicant has amended claim 1 to include the phrase “the fragmented collagen component is redispersible as determined by: after the fragmented collagen component is freeze-dried, a suspension having a concentration of 0.5% by mass of the fragmented collagen component in water and maintained at 20˚C exhibits a rate of change in light transmittance, for light having a wavelength of 500 nm, of 200% or less for 1 hour from a start of the suspension”.
The claimed property of redispersibility of the fragmented collagen component after being freeze-dried is deemed to be an inherent property of fragmented collagen that is derived from human or pig and has been thermally crosslinked to 12% as determined by TNBS with the average length of 100 micron, in powder form and fragmented using an ultrasonic homogenizer, baring evidence to the contrary.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-3, 8-9, 14-17, 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over Kamimura et al (JP 5169180-machine translation-previously cited) in view of Qin et al (US 2018/0044629-previously cited), Li et al (Ultrasonics Sonochemistry, 2009-previously cited), Madaghiele et al (Journal of Biomedical Materials Research Part A, published online 2015-newly cited) and Liu et al (Biomacromolecules 2006-newly cited) and as evidenced by Kondo et al (Materials Research 2014-previously cited).
Regarding claims 1-3, 14, and 19-20, Kamimura teach a composition comprising a collagen powder that is crosslinked (fragmented extracellular matrix component with at least a part that is crosslinked (page 5, claims). The powder is obtained by chopping a single yarn (fibrillar)(page 5, claims). Kamimura teach wherein their composition is to be used for treatment of damaged tissue (tissue repair) (page 5 Industrial Applicability). Kamimura disclose wherein the collagen may be derived from various tissue sources including pigs and humans (page 2 lines 12-13). Kamimura teach wherein the collagen powder is dispersible in an aqueous medium (page 3 paragraph 4).
Kamimura are silent with regard to the average length of the fragmented extracellular matrix component and the fragmented collagen component resulting from an ultrasonic homogenizer and the retention of a triple helix structure in the collagen.
Qin teach methods of preparing biologically functional scaffolds for use implantation for the repair of various tissue defects (page 1 para 3). The biological scaffold may contain collagen fibers to provide support and stability to the biological composition (page 6 para 57). The collagen fibers are taught to have an average length of 100 µm (page 7 para 60) and an average diameter of about 5, 10, 20 or 30 µm (page 7 para 58).
Li teach methods of using ultrasonic irradiation in the enzymatic extraction of fibrillar collagen for use in biomedical applications (Title, abstract, page 605). During the extraction process the ultrasonic treatment is administered during the mixing with pepsin (ultrasonic homogenization) (page 606, 2.experimental, section 2.1 and 2.2). The methods using ultrasonic treatment are shown to hold the triple helix structure derived from collagen (page 608, column 1, Fig 6). The enhanced efficiency of enzymatic extraction of collagen in the presence of ultrasound is attributed to the effective agitation caused by the ultrasonic cavitation (page 609, 4.Conclusion).
One of ordinary skill in the art would have been motivated to include collagen particles/fibers with an average length of about 100 µm and an average diameter of about 4 to 30 µm, or 20-30 µm in the method and compositions of Kamimura because Qin teach that collagen fibers of this dimension are suitable and desirable in a biological composition intended for implantation and repair of damaged tissue and Kamimura is also making biological collagen containing compositions for the same purpose. One of ordinary skill in the art would have been motivated to include the beneficial effect of collagen particles with the triple helical conformation of native collagen using the ultrasonic extraction technique suggested by Li. One of ordinary skill in the art would have had a reasonable expectation of success because Kamimura, Qin and Li are using fragmented fibrillar collagen matrix for the use in biomedical applications.
The combined teachings of Kamimura, Qin and Li render obvious the composition of claim 1 as described above, and Kamimura teach that multiple crosslinking steps can occur including a thermal crosslinking treatment (heat)(page 5), but are silent with regard to the crosslinking percentage of the composition.
Madaghiele disclose assessment of collagen crosslinking and denaturation for the design of regenerative scaffolds (Title). Coupling a mild DHT (thermal) treatment with further crosslinking may be very useful to modulate the crosslinking density but also to limit the amount of denaturation (abstract). The optimization of the DHT process to observing crosslinking and denaturation is suggested (page 192, Discussion). Conditions that include a DHT temperature of about 120 degrees C provide about 12% crosslinking and are suggested as desirable and beneficial and measured by a TNSB assay (page 191, Figure 3A, page 193 Conclusion).
Therefore, one of ordinary skill in the art would have been motivated to optimize the percentage of crosslinking in the collagen matrix scaffolds of Kamimura to be at around 12% because Madaghiele teach and suggest that this is a desirable crosslinking percentage when forming collagen-based matrices for tissue engineering scaffolds. One of ordinary skill in the art would have had a reasonable expectation of success because both Kamimura and Madaghiele are directed to forming collagen-based scaffolds for tissue engineering.
While Kamimura disclose wherein the collagen may be derived from various tissue sources including pigs and humans (page 2 lines 12-13), they do not include specific embodiments wherein the collagen is from pig or human tissue.
However, Liu disclose that porcine collagen and human collagen implants are preferred to bovine collagen as they are expected to be less prone to causing health problems, such as allergic responses and prion-transmitted diseases. Furthermore, the use of rhc (recombinant human collagen) implants will reduce immunological or allergic reactions and completely prevent the transmission of animal-related infectious agents (especially viral and prion-based) (page 1821, Results and Discussion).
Therefore, one of ordinary skill in the art would have been motivated to select collagen from pigs and humans rather than bovine collagen in the in the collagen matrix scaffolds of Kamimura because Liu teach and suggest that porcine and human sources are preferred over bovine sources. One of ordinary skill in the art would have had a reasonable expectation of success because Kamimura suggest that pigs and humans are suitable alternatives to cattle sources for collagen in their invention.
The claimed property of redispersibility of the fragmented collagen component after being freeze-dried is deemed to be an inherent property of fragmented collagen that is derived from human or pig and has been thermally crosslinked to 12% as determined by TNBS with the average length of 100 micron, in powder form and fragmented using an ultrasonic homogenizer, baring evidence to the contrary. Regarding the issue of inherency, see Persion Pharms. LLC v. Alvogen Malta Operations LTD., 945 F.3d 1184, 1191, 2019 USPQ2d 494084 (Fed. Cir. 2019), where the court stated that a proper finding of inherency does not require that all limitations are taught in a single reference, and that inherency may meet a missing claim limitation when the limitation is "the natural result of the combination of prior art elements." (emphasis in original). The court found that pharmacokinetic limitations of the asserted claims were inherently met by combining prior art references because the limitations were necessarily present in the prior art combination. Id. See also Hospira, Inc. v. Fresenius Kabi USA, LLC, 946 F.3d 1322, 1329-32, 2020 USPQ2d 6227 (Fed. Cir. 2020). (see MPEP 2112 (IV)).
Regarding claims 8-9, Kamimura teach wherein the collagen powder is combined with cells and used to form (formation agent) a 3D tissue construct (page 5 Industrial Applicability).
Regarding claims 15-17, the modification of the collagen fragments with ultrasonic treatment extraction (homogenization) as suggested by Li, produces collagen fragments that transmit light in a dispersed state (as evidenced by Kondo, page 8 section 3.2 Figure 5). Thus, baring evidence to the contrary, the collagen fragments produced through ultrasonic extraction (homogenization) and used in the composition of Kamimura, include the same structure as the claimed composition.
Therefore, the combined teachings of Kamimura et al, Qin et al, Li et al., Madaghiele et al and Liu et al render obvious Applicant’s invention as claimed.
Response to Arguments
Applicant's arguments filed 07/29/2025 have been fully considered but they are not persuasive given the new grounds of rejection presented above.
Applicant argues that their amendment to claim 15 to clarify the crosslinking percentage of the fragmented collagen component renders the Office’s interpretation of the claims as a product by process type claim.
This is not found persuasive. Applicant’s claims are drawn to a product and include limitations drawn to how the product is produced and thus these limitations render the claim a product by process type claim.
Applicant argues that the work of Davidenko is based on collagen and gelatin of bovine origin and does not teach or suggest the features of amended claim 1.
This is not found persuasive. The obviousness rejection has been modified and no longer relies on the teaching of Davidenko.
Applicant argues that according to their Declaration that bovine collagen has been found to be non-dispersible in testing. Applicant asserts that bovine collagen was non-uniform in comparison to porcine collagen.
This is not found persuasive as the current obviousness rejection includes evidence that it was known in the prior art that porcine and human collagen were preferred sources for collagen intended for therapeutic use as described above.
Applicant argues that their Declaration provides evidence that the present claims reflect unexpected results of water-dispersion stability which is supported by their Specification at paragraphs 37, 106-107 and Figure 6. Applicant asserts that the crosslinking temperature affects the property of re-dispersibility after a frozen fragmented collagen component and that a temperature of 200 degrees C is required.
This is not found persuasive. First, the evidence provided is not commensurate in scope with the claims. The claims do not require a specific temperature for the thermal crosslinking. In addition, the evidence does not disclose any crosslinking percentages above 12% wherein the claim requires this property for an open-ended range of “crosslinking percentage of at least 12% or more”.
In submitting evidence asserted to establish unobvious results, there is a burden on an applicant to indicate how the examples asserted to represent the claimed invention are considered to relate to the examples intended to represent the prior art and, particularly, to indicate how those latter examples do represent the closest prior art. See In re Borkowski, 595 F.2d 713, 184 USPQ 29 (CCPA 1974); In re Goodman, 339 F.2d 228, 144 USPQ 30 (CCPA 1964).
The evidence relied upon should also be reasonably commensurate in scope with the subject matter claimed and illustrate the claimed subject matter "as a class" relative to the prior art subject matter "as a class." In re Susi, 440 F.2d 442, 169 USPQ 423 (CCPA 1971 ); In re Hostettler, 429 F.2d 464, 166 USPQ 558 (CCPA 1970). See, also, In re Lindner, 457 F.2d 506, 173 USPQ 356 (CCPA 1972).
It should also be established that the differences in the results are in factunexpected and unobvious and of both statistical and practical significance. In reMerck, 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986); In re Longi, 759 F. 2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Klosak, 455 F2d 1077, 173 UAPQ 14 (CCPA 1972); In re D'Ancicco, 429 F.2d 1244, 169 USPQ 303 (CCPA 1971 ). Ex parte Gelles, 22 USPQ2d 1318 (BPAI 1992).
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Grover et al., “Crosslinking and composition influence the surface properties, mechanical stiffness and cell reactivity of collagen-based films”, Acta Biomaterialia, 2012, Vol. 8, pp. 3080-3093.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631