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 14-15, 17-18, and 30-31 are under examination.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 14-15,17-18, and 30-31 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claims contain subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventors, at the time the application was filed, had possession of the claimed invention. A new limitation has been added that states, “in each of the steps (a), (b), and (c) an artificial material that supports a structure of the three-dimensional cell mass being not mixed” The specification fails to provide insight into which structures are considered part of the 3D cell mass and which structure are considered supportive artificial material that are prohibited and/or not mixed. For example, it is unclear if the artificial material mentioned in the claims is part of the structure of the 3D cell mass or a substrate/structure that somehow supports the 3D cell mass such as a culture medium or a mesh support . The specification only states that its 3D cell mass can be scaffold free (one species example in which a supportive artificial material is not present).
“[T]he purpose of the written description requirement is to ‘ensure that the scope of the right to exclude, as set forth in the claims, does not overreach the scope of the inventor's contribution to the field of art as described in the patent specification.” Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1353-54 (Fed. Cir. 2010) (en banc) (quoting Univ. of Rochester v. G.D. Searle & Co., 358 F.3d 916, 920 (Fed. Cir. 2004)). To satisfy the written description requirement, the specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention.” Vas-Cath, Inc. v. Mahurkar, 935 F.2d 1555, 1562-63, 19 USPQ2d 1111 (Fed. Cir. 1991). See also MPEP 2163.04.
As described in MPEP § 2163, “The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice...reduction to drawings...or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus’...See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus."
The genus is a 3D cell mass without artificial support. In analyzing whether a representative number of species of the genus has been described so that one is able to comprehend the genus, the specification is first assessed to determine whether a representative number of species of the genus have been described so that one is able to comprehend the structure of the genus. The specification must make it clear what the variations in the genus are. The Scaffold Free section of the specification (Page 34) states the following: “A cell mass to be frozen with use of a composition for cryopreservation in accordance with an aspect of the present invention is preferably a scaffold-free, three-dimensional structure. As used herein, the term “scaffold-free” (framework-free, substrate-material-free) means that the structure contains substantially no material conventionally used to produce an artificial tissue (such a material is a substrate material, or a scaffold).” The paragraph does not provide better description of what framework free means. While the specification states that the 3D cell mass can have no interior framework; it does not preclude the use of a supportive mesh substrate for the cells in a cell sheet to lay on.
Conclusion: The specification only provides one example of a 3D structure without an artificial support material (a 3D structure without scaffolding). It is not clear what scaffolding encompasses. It is not clear if scaffolding encompasses a mesh that the cells of Miyagawa are placed on or if it is a more internal structure/framework. More specific examples of scaffolding are not present in the specification. The only species of a 3D cell mass without artificial support material is a scaffold free structure which is only vaguely described in the specification. Thus, applicant is not entitled to the entire genus of a 3D support structure without artificial support material.
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 14-15,17-18, and 30-31 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. A new limitation has been added that recites in claims 14 and 15, “in each of the steps (a), (b), and (c), an artificial material that supports a structure of the three-dimensional cell mass being not mixed.” The specification and/or instant claims do not establish what an artificial material encompasses for purposes of examination. It is not clear how a supportive artificial material differs from a 3D cell mass structure and/or if the supportive artificial material can include something like a mesh substrate support that does not provide interior framework support. For example, it is not clear if the artificial material is a type of structure or a type of medium. For purposes of examination, the former 103 rejection will be left in place until the claims are better clarified.
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 14-15, 17-18, and 30-31 are rejected under 35 U.S.C. 103 as being unpatentable over Miyagawa (WO 2016167332) in view of Herickhoff (US 20150037783) . Miyagawa (US 20180042220) is serving as an English translation for WO 2016167332 and will be referred to in this rejection.
Miyagawa teaches a method of producing a cryopreserved material obtained by freezing cells, the method comprising the following steps (a) and (c), the step (c) being carried out after the step (a): (a) immersing the cells in a cryopreservation medium (Paragraphs 11 and 81 of Miyagawa);
(c) freezing the cells in the cryopreservation medium (Paragraph 14 of Miyagawa),
the method further comprising step (b) of reducing an amount, relative to the cells, of the cryopreservation medium in which the cells are immersed, the step (b) being carried out after the step (a) (Paragraph 12 of Miyagawa), the cells which have been subjected to the step (b) being frozen in the step (c) (Paragraph 14 of Miyagawa),
the cells being mesenchymal stem cells in the form of a three-dimensional cell mass, wherein the three-dimensional cell mass is a three- dimensionally extending object (i) in which a matrix that has been produced by the mesenchymal stem cells is disposed three-dimensionally, (ii) in which cells are arranged three-dimensionally, and (iii) which contains cells that maintain bonds between them and the orientations thereof (Abstract and Paragraph 69),
the cryopreservation medium containing no cytokine (Paragraphs 91-93 of Miyagawa---cytokines are not required) as in instant Claims 14 and 15.
Miyagawa teaches a cryopreservation medium in paragraphs 91-92. Miyagawa does not teach that the cryopreservation medium includes fatty acids. Herickhoff teaches that fatty acids such as phosphatidic acid can be used in a cryopreservation medium (Paragraphs 51 and 53 of Herickhoff). It would have been obvious to an artisan of ordinary skill at the time of effective filing to have included in the phosphatidic acid of Herickhoff with the cryopreservation medium taught by Miyagawa. An artisan would have been motivated to have used phosphatidic acid (a fatty acid) in Miyagawa’s cryopreservation medium because it is a cryoprotectant that can be used to aide in the cryopreservation process as taught by Herickhoff paragraphs 51 and 53). Because the Herickhoff reference teaches that such an agent can be used to promote cryopreservation and protect the viable cells thus preserved, there would have been a high expectation for success (Paragraphs 51 and 53 of Herickhoff) as in instant Claims 14-15.
Dependent Claims taught by Miyagawa
Miyagawa teaches that step (b) includes bringing the cells into a state in which the cells are not immersed in the cryopreservation medium (Paragraphs 12 and 28 of Miyagawa) as in instant Claims 17 and 30.
Miyagawa teaches that step (c) includes freezing the cells at -80°C or below (Paragraph 90 of Miyagawa) as in instant Claims 18 and 31.
Miyagawa teaches a method of cryopreservation that includes exposing cells in a matrix (a cell sheet) to a cryopreservation agent/medium, then decreasing the amount of cryopreservation agent/cryopreservation medium before cryopreserving the cells. Miyagawa does not teach including a fatty acid within the cryopreservation medium. However, a skilled artisan would have been motivated to have included a fatty acid such as phosphatic acid because it can assist with the cryopreservation of cells as taught by Herickhoff. 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 predictable results to one of ordinary skill in the art at the time of the invention (See KSA 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 most likely will be knowledgeable and well-read in the relevant literature and have the practical experience in molecular biology, cell culture, and cryopreservation. Therefore, the level of ordinary skill in this art is high.
Response to Applicants Arguments/Amendments
Applicants state that the claim amendments are derived from the specification that teaches that a 3D cell mass was produced without mixing an artificial material for supporting the structure of a three-dimensional cell mass, such as a mesh-shaped support body. The problem with this amendment is that it is not clear what the artificial material encompasses. The specification does not provide examples of structures that cannot be included in the three-dimensional cell mass. Thus, there is a written description issue. An amendment could be added that states specifically what is in the 3D mass instead of describing the 3D structure using negative limitations.
Applicants argue that Miyagawa is an inappropriate reference to use because it is concerned with preventing breakage of a sheet-shaped cell culture that contains a mesh structure facilitating the removal of a cryopreservation solution. Applicants further state, “Indeed, such a person of skill would conclude that the object of Miyagawa is mainly mechanical protection of a sheet-shaped cell culture, and the object is attained mainly by the shape of the support body (the mesh) and its physical properties.”
The support body (mesh support) taught by Miyagawa is more of a substrate and not actually part of the main internal framework of the sheet that keeps the cells together. The mesh support of Miyagawa would not be considered mixed in with the cells. Since Miyagawa’s process is used in cryopreservation of cells, it would have been obvious to have included additional teachings that include protecting cells during cryopreservation.
Applicants further argue the combination of Miyagawa and Herickhoff. Applicants argue, “As described above, the effect yielded by Miyagawa depends on the physical shape and structure of the mesh-shaped support body. Hence, Miyagawa does not have a room for utilizing chemical and biological efforts of an additive such as phosphatidic acid and fatty acid [taught by Herickhoff]. Furthermore, Herickhoff does not describe that phosphatidic acid and fatty acid contribute to the solution of the aforementioned technical problem.”
Both the Miyagawa and the Herickhoff references are analogous art because they still teach methods of cryopreserving cells. An artisan would have been motivated to have combined the teachings of Herickhoff with those of Miyagawa because Herickhoff teaches that phosphatidic acid is able to promote successful cryopreservation and protect viable cells during the cryopreservation process (Paragraphs 51 and 53 of Herickhoff). There is motivation enough to add the phosphatidic acid because it protects cryopreserved cells.
Applicants argue, “The technical problem of Miyagawa is to prevent breakage of a sheet-shaped cell culture due to its fragility and effective removal of cryopreservation solution” not improving post-cryogenic cell viability as taught by Herickhoff. Miyagawa is concerned with improving the cryopreservation of its sheet-shaped cell culture (3D cell mass) (Abstract of Miyagawa). An artisan would have still been motivated to have added the phosphatidic acid taught by Herickhoff because it improves the viability of the cells during cryopreservation.
Applicants further argue that, “the sheet-shaped cell culture” in Miyagawa is essentially different from the three-dimensional cell mass in the present application….applicant feels that the “sheet-shaped cell culture” can be defined as follows: “(a) It is formed with cells connected to each other, (b) it has three-dimensional orientations, but has a higher orientation in a specific plane in particular, (c) although it is possible to laminate sheets, there is a limit in thickness because excessive thickness makes it impossible to supply nutrients and oxygen….” Applicants argue that this sheet-shaped cell culture disclosed in Miyagawa is clearly different than the three-dimensional cell mass in the present application. The sheet-shaped cell culture described by Miyagawa extends in three dimensions (width, height, and depth) so it would still be considered a 3D cell mass. The claims do not provide additional structures for the 3D cell mass that would further distinguish the 3D cell mass recited in the claims from the 3D cell mass disclosed in Miyagawa. Furthermore, the mesh support of Miyagawa can be viewed as a substrate and not as mixed within the cell sheet structure of Miyagawa.
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.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/Tracy Vivlemore/Supervisory Primary Examiner, Art Unit 1638