DETAILED CORRESPONDENCE
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
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 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 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 negatived by the manner in which the invention was made.
The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under pre-AIA 35 U.S.C. 103(a) 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 under pre-AIA 35 U.S.C. 103(a), the examiner presumes that the subject matter of the various claims was commonly owned at the time any inventions covered therein were made absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and invention dates of each claim that was not commonly owned at the time a later invention was made in order for the examiner to consider the applicability of pre-AIA 35 U.S.C. 103(c) and potential pre-AIA 35 U.S.C. 102(e), (f) or (g) prior art under pre-AIA 35 U.S.C. 103(a).
Claims 1-14 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Antwiler (PGPub 2008/0220523 [IDS Reference]) and Furcht, et al (US Pat. 7,015,037 [IDS Reference]) and evidenced by Whitford, et al (BioProcess Technical, 7, 54-63, 2009). Antwiler teaches a method of ex vivo expanding stem cells on a hollow fiber substrate. Antwiler specifically teaches that the substrate can be selectively modified to allow for stem cell adherence. See paragraphs [0005] [0006] [0055] [0122]. Antwiler teaches methods of harvesting cells, which by definition, would include removing the expanded cells from the hollow fiber substrate. Antwiler specifically notes that stem cells can be expanded/harvested by this method. See paragraphs [0127]-[0131]. While Antwiler does broadly teach stem cells, Antwiler does not teach the specifically claimed cells. However, purely based upon the disclosure of Antwiler, the ordinary artisan would expect that hollow fiber bioreactors would predictably ex vivo expand any type of stem cell. Although Antwiler does not explicitly state that the “hollow fiber substrate is in a closed perfusion bioreactor,” based upon terms used throughout the disclosure, it would suggest that the system of Antwiler also provides for the same limitation. For example, Antwiler continually states that the system comprises “flow circuits,” and “circulation paths,” wherein the fluid flow is driven by a peristaltic pump. See paragraphs [0006]-[0011] and [0100]-[0105]. Additionally, Antwiler defines these “circulation paths” as “loops,” suggesting a closed perfusion system. See paragraph [0040]. Coupling this information with the figures provided by Antwiler would inform the ordinary artisan that the system of Antwiler achieves the claimed limitations. It should also be noted that the system of Antwiler must be compatible with the claim limitations, since it is explicitly stated in the instant specification that the system of Antwiler is used in the claimed method. See paragraph [0193] of the instant specification.
Furcht teaches adherent stem cells that are non-embryonic, non-germ cells; the cells express telomerase, possess a normal karyotype, and are not transformed. See column 6, lines 3 and 60; column 16, line 8. It can be reasoned that Furcht’s cells are not transformed because Furcht does not describe transformation of the stem-like cell. Furcht suggests that these cells can be applied to a hollow fiber bioreactor system. See column 31, lines 44 and 45. While Furcht does state that these cells can be genetically altered there is nothing in Furcht or Antwiler to suggest that unmodified cells would be capable of being effectively expanded. Furcht indicates that the cells are capable of a significant number of doublings, wherein the cell maintains its pluripotent status. See column 6, lines 59-67; column 15, lines 60-67. As such, there is nothing unpredictable about using the cells of Furcht, that have been doubled 10-40 times, since there is an expectation that the cells will be nearly identical to each other regardless of the number of doublings (to a point). Additionally, the instant specification explicitly states that the cells of Furcht are those that are claimed. See paragraph [0095] [0097] [0163] [0165] [0166] [0170] [0176] [0181].
Whitford provides a general idea of what the ordinary artisan would be aware of, regarding hollow fiber bioreactor state-of-the-art, prior to the effective filing date of the instant invention. Whitford specifically notes that, broadly speaking, hollow fiber bioreactors can be of particular utility when expanding stem cells. Page 58, Table 1; pages 62 and 63, “Stem Cells” section. Based upon the disclosures of Antwiler and Furcht, and further confirmed by Whitford, the ordinary artisan would find it obvious to expand the cells of Furcht in the hollow fiber bioreactor of Antwiler, because Furcht teaches the expansion of cells with therapeutic utility (see column 8, lines 1-4), and both Antwiler and Whitford teach that stem cells can be reliably and effectively expanded using hollow fiber bioreactors. The ordinary artisan would expect the stem cells of Furcht to be predictably expanded using the hollow fiber bioreactor method of Antwiler.
Antwiler teaches that adherent mesenchymal stem cells can be predictably expanded in a hollow fiber system, and Furcht teaches that the claimed cells are adherent cells that are a subpopulation of bone marrow-derived mesenchymal stem cells. See column 10, lines 20-30; columns 44 and 45, Example 1. Furthermore, Antwiler notes that mesenchymal stem cells will adhere to substrates treated with fibronectin, and Furcht notes that the claimed cell population is adherent to fibronectin. See Antwiler, paragraphs [0055] [0059] [0120] [0123]; see Furcht, column 15, lines 5 and 6; column 18, lines 9-25; columns 44 and 45, Example 1. Based upon this analysis, the ordinary artisan would predict that if the hollow fibers of Antwiler were coated with fibrionectin, there would be an expectation that the cells of Furcht would be capable of expanding on the fibronectin hollow fibers. This is reasonable because Furcht teaches that the instantly claimed cells, which are a subpopulation of adherent mesenchymal stem cells, can be expanded on a culture plate that is coated with fibronectin.
With respect to claim 1, Antwiler teaches an identical method of ex vivo expanding adherent stem cells, by using a hollow fiber bioreactor. Furcht teaches stem cells that are identical to those claimed. Since Antwiler teaches the general expansion of stem cells using hollow fiber bioreactors, and Whitford indicates that the ordinary artisan is already aware that stem cells are particularly suitable for hollow fiber bioreactor expansion, it would be obvious to the ordinary artisan to expand the stem cells of Furcht, using the stem cell expanding hollow fiber bioreactor method taught by Antwiler. There would be an expectation of success because there is nothing of record to suggest that there would be any expectation that the stem cells of Furcht would be incompatible with the hollow fiber bioreactor of Antwiler; furthermore, the ordinary artisan would expect that the hollow fiber bioreactor method of Antwiler would predictably expand the cells of Furcht.
With respect to claim 2, Furcht teaches that the substrates can be reseeded, wherein they are doubled at least 40 times, suggesting that the steps of expanding, removing and reseeding cells are repeated as many times as the ordinary artisan desires. See column 16, lines 49-51. It should further be noted that a general method of expanding cells, by seeding, expanding, removing, and repeating the three steps is how the ordinary artisan would perform a cell population expansion, since this is common in the art.
With respect to claim 3, Furcht teaches the pharmacological utility of the claimed cells, as well as methods of administering the claimed cells. See column 7, lines 42, 43 and 53-60.
With respect to claim 4, Furcht teaches that the cells are capable of at least 40 doublings. See column 16, lines 49-51.
With respect to claims 5 and 6, Antwiler teaches that the hollow fibers can be coated with fibronectin. See paragraph [0123].
With respect to claim 7, Antwiler teaches a hollow fiber bioreactor constructed with PA/PAES/PVP. See paragraph [0056].
With respect to claim 8, Furcht teaches that the further expansion of the instantly claimed cells leads to increasingly homogenous populations. See column 16, lines 49 and 50.
With respect to claim 9, Furcht teaches that the cells express oct3/4 (synonymous with oct4), Rex-1, Rox-1 and Sox-2. See column 18, lines 5-7.
With respect to claims 10, 11 and 13, Furcht teaches that the cells can differentiate into any of endodermal, ectodermal or mesodermal-lines. See column 6, lines 8-11.
With respect to claims 12 and 14, Furcht indicates that the cells are marrow-derived. Column 1, line 21. Furcht indicates that the cells can be derived from humans. See column 6, line 16.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DAVID W BERKE-SCHLESSEL whose telephone number is (571)270-3643. The examiner can normally be reached M-F 8AM-5:30PM.
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, Melenie Gordon can be reached at 571-272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/DAVID W BERKE-SCHLESSEL/Primary Examiner, Art Unit 1651
Prosecution Insights