The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
This action is responsive to papers filed 06/18/2025
Claims 24, and 39-40 have been amended. Claims 31-34, 38, 43, and 45-46 have been newly canceled and claims 47-53 have been newly added.
Claims 24, 26-27, 35-37, 39-42, 44, and 47-53 are currently pending.
Claim 44 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 01/09/2019.
Claims 37 and 39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 01/09/2019.
Claims 24, 26-27, 35-36, 40-42, 44, and 47-53 have been examined on their merits.
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn due to amendment. The following rejections and/or objections are either reiterated or newly applied. They constitute the complete set presently being applied to the instant application.
Information Disclosure Statement
The information disclosure statement (IDSs) submitted on 06/18/2025 has been considered by the examiner.
Claim Interpretation
The transitional phrase “consisting essentially of” limits the scope of a claim to the specified materials or steps and those that do not materially affect the basic and novel characteristic(s) of the claimed invention. A “consisting essentially of” claim occupies a middle ground between closed claims that are written in a consisting of format and fully open claims that are drafted in a comprising format. For the purposes of searching for and applying prior art under 35 U.S.C. 102 and 103, absent a clear indication in the specification or claims of what the basic and novel characteristics actually are, “consisting essentially of” will be construed as equivalent to “comprising.” See, MPEP 2111.03 and 2163.
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 of this title, 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 24, 26-27, 35-36, 40-42, 47 and 53 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Kuo et al (US 2010/0047853-previously cited).
Regarding claims 24 and 53, Kuo disclose a composition comprising a three-dimensional organoid having a lumen surrounded by cells that comprise a combination of in vitro expanded Lgr5+ adult epithelial stem cells and differentiated epithelial stem cell progeny, wherein the cells are derived from one or more Lgr5+ adult epithelial stem cells from an adult tissue and further comprising an exogenous extracellular matrix (page 1 para 8, page 2 para 23, page 3 para 33 para 36, page 4 para 46 para 50, page 13 example 4 para 128-132).
Regarding claims 26-27, Kuo disclose wherein the exogenous extracellular matrix is Matrigel which is obtained from EHS mouse sarcoma cells and contains collagen (page 4 para 50, page 15 para 149).
Regarding claim 35, Kuo disclose wherein their epithelial cells are adult, human (page 3 para 33) and include epithelial stem cells (page 3 para 36).
Regarding claim 36, Kuo disclose wherein their intestinal epithelial cells are carcinoma cells (page 1 para 9, page 5 para 58, page 10 para 104).
Regarding claim 40, Kuo disclose wherein their ultrastructure refers to three-dimensional structure of intestinal epithelium observed in vivo and that this includes the polarity of the intestinal epithelial cells (random orientation towards either the periphery or lumen) and the morphology observed in the intestinal epithelium, such as the presence of crypt structures (page 4 para 48).
Regarding claim 41, Kuo are silent with regard to presence of nuclear beta-catenin in their epithelial structures cells, however Applicant’s specification teaches that when a Wnt agonist is added to the culture medium that this results in enriched nuclear beta-catenin (page 8 line 28-page 29 line 2). Since Kuo includes a Wnt agonist in their culture medium that activates the beta-catenin dependent signaling (page 4 para 49), the nuclear beta-catenin is deemed to be inherently enriched as well.
Regarding claim 42, Kuo disclose freezing their cultured cells at temperatures lower than -5˚C (page 16 para 159).
Regarding claim 47, Kuo include wherein their composition includes a culture medium (page 2 para 14, page 4 para 42, pages 4-5 para 51, pages 5-6 para 63-65).
The specific combination of features claimed is disclosed within the broad genera of epithelial cell types, sources, culture and storage conditions taught by Kuo, but such “picking and choosing” within several variables does not necessarily give rise to anticipation. Corning Glass Works v. Sumitomo Elec., 868 F.2d 1251, 1262 (Fed. Circ. 1989). Where, as here, the reference does not provide any specific teaching to select this specific combination of variables, anticipation cannot be found.
That being said, however, it must be remembered that “[w]hen a patent simply arranges old elements with each performing the same function it had been known to perform and yields no more than one would expect from such an arrangement, the combination is obvious”. KSR v. Teleflex, 127 S.Ct. 1727, 1740 (2007) (quoting Sakraida v. A.G. Pro, 425 U.S. 273, 282 (1976)). “[W]hen the question is whether a patent claiming the combination of elements of prior art is obvious”, the relevant question is “whether the improvement is more than the predictable use of prior art elements according to their established functions.” (Id.). Addressing the issue of obviousness, the Supreme Court noted that the analysis under 35 USC 103 “need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ.” KSR v. Teleflex, 127 S.Ct. 1727, 1741 (2007). The Court emphasized that “[a] person of ordinary skill is… a person of ordinary creativity, not an automaton.” Id. at 1742.
Consistent with this reasoning, it would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have selected various combinations of epithelial cell types, sources, culture and storage conditions from within the disclosure of Kuo to arrive at methods and compositions “yielding no more than one would expect from such an arrangement”.
The motivation and reasonable expectation of success in making these combinations comes from the fact that Kuo suggests that all these cited variables are suitable for inclusion in their method/composition.
Therefore, the teaching of Kuo et al renders obvious Applicant’s invention as claimed.
Claims 47-51 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Kuo et al (US 2010/0047853-previously cited) as applied to claims 24, 26-27, 35-36, 40-42, 47 and 53 above, and further in view of Guha et al (WO 2008/101215-from IDS filed 10/23/2017).
Regarding claims 47-51, Kuo disclose including a culture medium that contains growth factors (page 4 para 42) such as R-spondin 1 (page 4 para 49, page 6 para 65, and FGF (page 11 para 112), but do not specifically teach including a BMP inhibitor.
Guha disclose a culture medium for the expansion of ex vivo cells wherein the cells are human, adult stem cells and intestinal cells and the mitogenic growth factors include one or more of HGF, EGF, FGF, Noggin (BMP inhibitor), and R-spondin 1 (pages 11-12 para 31, pages 22-23 para 70, page 63 claims 38-39).
One of ordinary skill in the art would have been motivated with a reasonable expectation of success to include the mitogenic growth factors of HGF, EGF, FGF and Noggin in addition to R-spondin 1 in the culture medium of Kuo because Guha teach and suggest that these are suitable and beneficial mitogenic growth factors for the expansion of cells that include adult stem cells of the intestines.
Therefore, the combined teachings of Kuo et al and Guha et al render obvious Applicant’s invention as claimed.
Claim 52 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Kuo et al (US 2010/0047853-previously cited) in view of Guha et al (WO 2008/101215-from IDS filed 10/23/2017) as applied to claims 47-51 above, and further in view of Sala et al (Developmental Biology 2006) and Li et al (Current Medicinal Chemistry, 2006).
Regarding claim 52, the combined teachings of Kuo et al and Guha et al render obvious the claimed invention as described above, and include FGF in the culture medium, but do not specifically teach wherein the FGF is FGF-10 or the inclusion of nicotinamide in the culture medium.
Sala disclose that fibroblast growth factor 10 is required for the survival and proliferation of intestinal epithelial progenitor cells (Title, abstract, page 382).
One of ordinary skill in the art would have been motivated to include FGF-10 in the culture medium of Kuo as the type of FGF because Sala disclose that fibroblast growth factor 10 is required for the survival and proliferation of intestinal epithelial progenitor cells. One of ordinary skill in the art would have had a reasonable expectation of success because both Kuo and Guha teach and suggest that FGF is suitable and desirable for the culture human adult intestinal stem cells.
Li disclose that nicotinamide plays a significant role during the enhancement of cell survival as well as cell longevity (abstract) and is rapidly absorbed through intestinal epithelium (page 1, page 7). The ability of nicotinamide to function as an essential cellular nutrient as well as assist and guide the development of progenitor cells appears to provide nicotinamide with essential qualities also necessary to protect cells against toxic insults (page 7, Table 1).
One of ordinary skill in the art would have been motivated to include nicotinamide in the culture media of Kuo because Li disclose that nicotinamide plays a significant role during the enhancement of cell survival as well as cell longevity (abstract). The ability of nicotinamide to function as an essential cellular nutrient as well as assist and guide the development of progenitor cells appears to provide nicotinamide with essential qualities also necessary to protect cells against toxic insults (page 7, Table 1). One of ordinary skill in the art would have had a reasonable expectation of success because Li disclose that nicotinamide is rapidly absorbed through intestinal epithelium (page 1, page 7) and Kuo is directed to culturing intestinal epithelial cells.
Therefore, the combined teachings of Kuo et al, Guha et al, Sila et al and Li et al render obvious Applicant’s invention as claimed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the claims at issue are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO internet Web site contains terminal disclaimer forms which may be used. Please visit http://www.uspto.gov/forms/. The filing date of the application will determine what form should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 24, 26-27, 35-36, 40-42, 44, 47-51 and 53 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 9,752,124.
Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of the patent are also drawn to an organoid obtainable by a similar method that does not appear to be structurally different from the currently claimed organoid.
The patented composition comprises a three-dimensional organoid obtained by in vitro expansion of one ore more adult adenoma stem cells with a sealed central lumen lined by epithelial cells comprising cells expressing Lgr5, with an exogenous extracellular matrix and a culture medium.
Therefore, the claims of the patent render obvious the claims of the current application.
Response to Arguments
Applicant’s arguments with respect to claim(s) 24, 26-27, 35-36, 40-42, 44, and 47-53 have been considered but are moot because the new ground of rejection does not rely on any reference applied in the prior rejection of record for any teaching or matter specifically challenged in the argument.
Conclusion
No claims are allowed.
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 LAURA J SCHUBERG whose telephone number is (571)272-3347. The examiner can normally be reached on 8:30-5:00 EST.
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LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/ Primary Examiner, Art Unit 1631