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 .
Claims 1-6, and 8-11 are under examination.
Claim Objections
Claims 1,4,6,8,9-10 is objected to because of the following informalities: “spheroid “ should be spheroids.
Response to Arguments Against the Objection
The artificial cartilage tissue is formed by the fusion of multiple spheroids, not just one. To better clarify the invention, it would be helpful to use the plural form of spheroids, rather than the singular term.
Response to Applicants Amendments/Arguments
The limitations from claim 7 have been amended and moved to claim 1 which discusses spheroid development in detail. The scope of the claims have been changed because of the amendment. Therefore, the former rejections are withdrawn and new rejections put forward. Thank you for amending claims 2-3, the 112(b) rejection has been withdrawn.
Claim Rejections - 35 USC § 103
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.
Claims 1,4-6,8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Le “Production of engineered cartilage from mesenchymal stem cell spheroids” Frontiers in Bioscience, Landmark, 26, 266-285, 2021 in view of Mendes “Advancing osteochondral tissue engineering: bone morphogenetic protein, transforming growth factor, and fibroblast growth factor signaling drive ordered differentiation of periosteal cells resulting in stable cartilage and bone formation in vivo” Stem Cell Res Ther. 2018 Feb 21; 9(1): 42 and Van Osch (WO2019073079)
Le teaches a method for creating an artificial cartilage tissue, comprising making chondrocyte progenitor cell-containing spheroids into a desired shape while seeding the spheroids on a support; culturing the spheroids while feeding a culture medium from both the obverse and reserve sides of the spheroid-seeded surface to therapy perform fusion among the spheroids, and maturing the resultant fused spheroids into a cartilage tissue in vitro (Pages 268-269 of Le) as in instant Claim 1.
Le does not teach culturing a chondrocyte progenitor cell in a culture medium containing TGF-beta, bFGF (FGF), and Wnt/B-catenin inhibitor in order to assist with the development of a chondrocyte progenitor containing spheroid. Mendes teaches that progenitor cells can be cultured in a medium containing a growth factor cocktail comprising TGF-beta, BMP2, growth differentiation factor (GDF)5, BMP6, and FGF2/bFGF to help generate spheroids/aggregates capable of producing cartilage (Abstract of Mendes). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have included Mendes culture components/medium. An artisan would have been motivated to have included Mendes medium since it produces spheroids/aggregates capable of producing cartilage (Abstract and Pages 4-5 of Mendes). Since such medium induces the production of chondrocytes/cartilage, there would have been a high expectation for success (Abstract and Pages 4-5 of Mendes) as in instant Claims 1 and 8.
Van Osch further teaches that TGF-B and a Wnt inhibitor/IWP2 encourages chondrogenic differentiation (Paragraph 65 of Van Osch). It would have been obvious to an artisan of ordinary skill in the art to have also included these components taught in Van Osch. An artisan would have been motivated to have included these components because they encourage chondrogenic differentiation and the production of cartilage (Paragraph 65 of Van Osch). Because such components can encourage the development of chondrocytes/cartilage, there would have been a high expectation for success as in instant Claim 1.
Dependent Claims taught by Le
Le discloses wherein the chondrocyte progenitor cell -containing spheroids are 20-1000 µm in diameter (Figure 3 and Page 272 of Le) as in instant Claim 4. Le discloses wherein one spheroid contains 100-7500 chondrocyte progenitor cells (Figure 4 and Page 272 of Le) as in instant Claim 5. Le discloses wherein the chondrocyte progenitor cell-containing spheroids have been prepared by culturing chondrocyte progenitor cells in a culture vessel having a non-cell adhesive surface (Abstract and Page 268 of Le; the surface does not involve adhesive feeder cells) as in instant Claim 6. Le discloses wherein the time period of culture of the fused spheroids for maturing into a cartilage tissue is 14-42 days (Page 268, Section 3.6 Chondrogenic induction of spheroid-scaffold complexes) as in instant Claim 9, Le further teaches a culturing time of 30 days, not a time period of 42-84 days. MPEP § 2144.05 (II) states the following: Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In reAller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 (“The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages.”); In reHoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc.v.Biocraft Lab. Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In reKulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997); Smith v. Nichols, 88 U.S. 112, 118-19 (1874) (a change in form, proportions, or degree “will not sustain a patent”): In re Williams, 36 F.2d 436, 438 (CCPA 1929) (‘It is a settled principle of law that a mere carrying forward of an original patented conception involving only change of form, proportions, or degree, or the substitution of equivalents doing the same thing as the original invention, by substantially the same means, is not such an invention as will sustain a patent, even though the changes of the kind may produce better results than prior inventions.”). See also KSR Int’ | Co. v. Teleflex Inc., 550 U.S. 398, 416 (2007) (identifying “the need for caution in granting a patent based on the combination of elements found in the prior art.”).
A review of the specification fails to provide evidence that the amount of time in culture (impacting amount exposure of elements in the culture) carries patentable weight. Absent such evidence it would have been obvious to an artisan of ordinary skill at the time of effectively filing Le to try a number of different culture time periods to see which one arrived at the most desirable type and/or amount of cartilage. An artisan would have a reasonable expectation of success in optimizing the concentration/exposure culture conditions/culture medium because such optimization was long established in the art as demonstrated by Le. Thus, Le renders the culture time period above in claim 10. Le discloses transplanting the cartilage tissue matured in vitro into a non-human animal and maturing the cartilage tissue furthermore (Page 269, Section 3.10 In vivo functions of cartilage tissues formed from spheroid-scaffold complexes section) as in instant Claim 11.
Le teaches culturing cartilage progenitor cells to generate cartilage tissue using a mesh support. Le does not teach culturing a chondrocyte progenitor cell in a culture medium containing TGF-beta, bFGF, and Wnt/beta-catenin inhibitor. However, an artisan would have been motivated to have included these components in the culture medium since Mendes and Van Osch teach that these components promote chondrogenic differentiation. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicants’ invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predicable results to one of ordinary skill in the art at the time of the invention (See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people will most likely be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology and microbiology. Therefore, the level of ordinary skill in this art is high.
Claims 1-2,4-6,8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Le “Production of engineered cartilage from mesenchymal stem cell spheroids” Frontiers in Bioscience, Landmark, 26, 266-285, 2021 in view of Mendes “Advancing osteochondral tissue engineering: bone morphogenetic protein, transforming growth factor, and fibroblast growth factor signaling drive ordered differentiation of periosteal cells resulting in stable cartilage and bone formation in vivo” Stem Cell Res Ther. 2018 Feb 21; 9(1): 42, Van Osch (WO2019073079), and Takarada (WO2021054449 in which USPG 20220372443 can serve as a translation).
Le, Mendes, and Van Osch apply as above to teach claims 1,4-6,8-11. Le does not teach that its progenitor cells are derived from IPS/embryonic stem cells/pluripotent stem cells. However, Takarada discloses that IPS/embryonal/pluripotent stem cells can be differentiated into a chondrocyte progenitor cell population (Paragraph 54 of Takarada). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have generated cartilage progenitor cells form IPS/embryonal/pluripotent cells as taught by Takarada. An artisan would have been motivated to have generated cartilage progenitor cells from IPS/embryonal/pluripotent stem cells since they are a readily available population of cells which can be easily obtained and further differentiated into more mature populations of chondrocyte progenitor cells (Paragraph 54 and Figure 62 of Takarada) as in instant Claims 2.
Le teaches culturing cartilage progenitor cells to generate cartilage tissue using a mesh support. Le does not teach culturing a chondrocyte progenitor cell in a culture medium containing TGF-beta, bFGF, and Wnt/beta-catenin inhibitor. However, an artisan would have been motivated to have included these components in the culture medium since Mendes and Van Osch teach that these components promote chondrogenic differentiation. Le does not teach generating the progenitor cells from IPS/embryonal/pluripotent cells. However, Takarada teaches that embryonal stem cells/IPS/pluripotent stem cells can successfully be used to generate cartilage tissue/cartilage progenitor cells. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicants’ invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predicable results to one of ordinary skill in the art at the time of the invention (See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people will most likely be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology and microbiology. Therefore, the level of ordinary skill in this art is high.
Claims 1,3-6,8-11 are rejected under 35 U.S.C. 103 as being unpatentable over Le “Production of engineered cartilage from mesenchymal stem cell spheroids” Frontiers in Bioscience, Landmark, 26, 266-285, 2021 in view of Mendes “Advancing osteochondral tissue engineering: bone morphogenetic protein, transforming growth factor, and fibroblast growth factor signaling drive ordered differentiation of periosteal cells resulting in stable cartilage and bone formation in vivo” Stem Cell Res Ther. 2018 Feb 21; 9(1): 42, Van Osch (WO2019073079), and Kovalev (RU 2731314)
Le, Mendes, and Van Osch apply as above to teach claims 1,4-6,8-11. Le does not teach that the chondrocyte progenitor cells can be obtained by differentiating perichondrocytes that are collected from perichondrium. Kovalev teaches that chondrocyte progenitor cells can be obtained by differentiating perichondrocytes collected from the perichondrium. It would have been obvious to an artisan of ordinary skill at the effective filing to have differentiated the perichondrocytes as taught in Kovalev into progenitor cells (Detailed disclosure of the invention and Paragraphs 1-3 of Kovalev). An artisan would have been motivated to have differentiated cells derived from the perichondrium because they can successfully generate chondrocyte progenitor cells which can be used in the present invention. Because such cells can generate chondrocyte progenitor cells, there would have been a high expectation for success (Detailed disclosure of the Invention, Paragraphs 1-3 of Kovalev) as in instant Claim 3.
Dependent Claims taught by Kovalev
Kovalev teaches wherein the chondrocyte progenitor cell-containing spheroids are 20-1000 µm in diameter (Disclosure of the Invention) as in instant Claim 4. Kovalev teaches wherein the chondrocyte progenitor cell-containing spheroids have been prepared by culturing chondrocyte progenitor cells in a culture vessel having a non-cell adhesive surface (Detailed Disclosure of the Invention Section in Kovalev states that the adhesive is agarose not feeder cells) as in instant Claim 6, Kovalev teaches wherein the time period of culture of the fused spheroid for maturing into a cartilage tissue is 14-42 days (Claim 6 of Kovalev) as in instant Claim 9.
Le teaches culturing cartilage progenitor cells to generate cartilage tissue using a mesh support. Le does not teach culturing a chondrocyte progenitor cell in a culture medium containing TGF-beta, bFGF, and Wnt/beta-catenin inhibitor. However, an artisan would have been motivated to have included these components in the culture medium since Mendes and Van Osch teach that these components promote chondrogenic differentiation. Le does not teach that chondrocytes can be generated from perichondrocytes from the perichondrium. However, an artisan would have been motivated to have differentiate the perichondrocytes from the perichondrium as taught in Kovalev since they can successfully generate progenitor cells. Given the teachings of the cited references and the level of skill of an ordinary skilled artisan at the time of applicants’ invention, it must be considered, absent evidence to the contrary, that the ordinary skilled artisan would have had a reasonable expectation of success in practicing the claimed invention.
All of the claimed elements were known in the prior art, and one skilled in the art could have combined the elements as claimed by known methods with no change in their respective functions, and the combination would have yielded predicable results to one of ordinary skill in the art at the time of the invention (See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007). People of ordinary skill in the art will be highly educated individuals, possessing advanced degrees, including M.D.s and Ph.D.s. They will be medical doctors, scientists, or engineers. Thus, these people will most likely be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology and microbiology. Therefore, the level of ordinary skill in this art is high.
Conclusion
All claims stand rejected.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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 LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Tracy Vivlemore can be reached at 571-272-2914. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638
