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 .
Election/Restrictions
Applicant’s election of Group I, claims 1-6, 10-12, 14, 16, and 25-28, in the reply filed on 05/06/2026 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 32, 34, and 38 are being rejoined with Group I and examined below.
Claims 40-41 and 47 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Group, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 05/06/2026.
Status of the Claims
Claims 1-6, 10-12, 14, 16, 25-28, 32, 34, 38, 40-41, and 47 are currently pending.
Claims 4-6, 10-12, 14, 16, 25-28, 32, 34, 38, 40-41, and 47 are amended.
Claims 40-41 and 47 have been withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected Invention, there being no allowable generic or linking claim.
Claims 7-9, 13, 15, 17-24, 29-31, 33, 35-37, 39, 42-46, and 48-51 are cancelled.
Claims 1-6, 10-12, 14, 16, 25-28. 32, 34, and 38 have been considered on the merits.
Claim Objections
Claim 28 objected to because of the following informalities: claim 28 appears to contain a typo where “RXR” should be amended to “FXR”. The term “RXR” does not appear in the specification, thus the recitation of RXR in claim 28 is being interpreted to be a typo of “FXR”. Appropriate correction is required.
Specification
The use of the term GentleMACS™, autoMACS™, MACS™ (at least throughout the Examples), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1 and 32 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chen et al (Biofabrication, 2018).
Regarding claim 1, Chen teaches providing a population of cholangiocytes and culturing the population of cholangiocytes in the presence of a FXR agonist to produce a population of FXR-treated cholangiocytes (pg. 3, col. 1, last para)
Regarding claim 32, Chen teaches an isolated population of FXR-treated cholangiocytes produced by the method of claim 1 (pg. 3 col. 1, last para spanning col. 2).
Therefore, Chen renders claim 1 obvious.
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.
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 2 is rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (Biofabrication, 2018), as applied to independent claim 1 above, and in further view of Singh et al (Translational Science, 2018).
With regards to claim 2, the limitations of the independent claim 1 are taught by Chen above.
Chen does not teach that the FXR agonist is selected from chenodeoxylic acid (CDA) or obeticholic acid (OCA) as required by claim 2. Chen does teach the use of the FXR agonist GW4064 (pg. 3, col. 1, last para).
However, Singh teaches the examination of the effects of three different FXR agonists including GW4064, FXR-450 and OCA on human liver cells and found that “All 3 agonists at effective doses elevated LDLR mRNA and protein levels to similar extents (Figure 5D and 5E)” (see pg. 2455, col. 1, para 2).
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of treating cholangiocytes with an FXR agonist taught by Chen with the specific OCA FXR agonist taught by Singh to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Singh teaches that “All 3 agonists at effective doses elevated LDLR mRNA and protein levels to similar extents (Figure 5D and 5E)” (see pg. 2455, col. 1, para 2). One of ordinary skill in the art would have a reasonable expectation of success when combining Chen with Singh because Singh teaches that GW4064 and OCA produce similar results in human liver cells and Chen teaches the necessary information to produce a FXR treated population of cholangiocytes.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Claims 3-6, 10-12, 14, 16, 25-28, 34, and 38 are rejected under 35 U.S.C. 103 as being unpatentable over Chen et al (Biofabrication, 2018), as applied to independent claim 1 above, and in further view of Vallier et al (WO 2018234323 A1).
Claim interpretation: Dependent claim 28 contains the term “RXR”, which does not appear in the specification, thus the recitation of RXR in claim 28 is being interpreted to be a typo of “FXR” and has been objected to above.
Regarding claims 3-6, 10-12, 14, 16, 25-28, 34, and 38, the limitations of the independent claim 1 are taught by Chen above.
Regarding claims 4, 16, and 28, Chen teaches the treatment of cholangiocytes with the FXR agonist (pg. 3, col. 1, last para).
Chen does not teach the required limitations of dependent claims 3-6, 10-12, 14, 16, and 25-28.
However, Vallier teaches methods of expanding cholangiocytes (pg. 2 lines 5-9). Vallier teaches that the combination of a canonical Wnt signal inhibitor and a non-canonical Wnt/PCP signaling potentiator “unexpectedly allow the efficient expansion of primary cholangiocytes in the form of cholangiocyte organoids” (pg. 2, lines 5-9).
Regarding claim 3, Vallier teaches that the cholangiocytes are primary cholangiocytes (pg. 2, lines 5-10) or iPSC derived (pg. 5, lines 11-13).
Regarding claim 4, Vallier teaches wherein the population of cholangiocytes is cultured in an expansion medium comprising EGF, a canonical wnt inhibitor and a non-canonical wnt potentiator (pg. 2, lines 10-16).
Regarding claim 5, Vallier teaches wherein the treated cells form organoids in the expansion medium of claim 4 (pg. 2, line 18).
Regarding claim 6, Vallier teaches wherein the cholangiocytes are extrahepatic cholangiocytes, intrahepatic cholangiocytes, or gallbladder cholangiocytes (pg. 2, line 36 and pg. 8, lines 27-30).
Regarding claim 10, Vallier teaches that the non-canonical wnt signalling potentiator is a wnt agonist (pg. 2, lines 20-21).
Regarding claim 11, Vallier teaches that the wnt agonist is R-spondin (pg. 2, lines 20-21).
Regarding claim 12, Vallier teaches that the canonical wnt signalling inhibitor is DKK-1 (pg. 2, line 23) .
Regarding claim 14, Vallier teaches wherein the population is cultured in a 3D culture in the expansion medium of claim 4 (pg. 2, lines 25-26).
Regarding claim 16, Vallier teaches wherein the expansion medium of claim 1 comprises a scaffold matrix and a nutrient medium supplemented with EGF, the canonical wnt inhibitor, and the non-canonical wnt potentiator (pg. 13, lines 9-12 and lines 32-34).
Regarding claim 25, Vallier teaches wherein the cholangiocytes are cultured in the expansion medium for 20 or more passages (pg. 14, lines 36-37 spanning line 1 of pg. 15).
Regarding claim 26, Vallier teaches wherein the method comprises disrupting cholangiocyte organoids such that the expanded population comprises individual cells (pg. 2, lines 28-30).
Regarding claim 27, Vallier teaches the method comprises seeding the population of cholangiocytes into a biocompatible scaffold, optionally within the scaffold matrix is a decellularized human or non-human tissue extracellular matrix (pg. 20, line 25 spanning pg. 21 line 7).
Regarding claim 28, Vallier teaches the method comprises culturing the biocompatible scaffold in an expansion medium comprising EGF, a canonical wnt signaling inhibitor and a non-canonical wnt signaling potentiator such that the cholangiocytes populate the scaffold (pg. 13, lines 14-20 and lines 32-34.
Regarding claim 34, Vallier teaches the method comprises seeding the population of cholangiocytes into a biocompatible scaffold, optionally within the scaffold matrix is a decellularized human or non-human tissue extracellular matrix (pg. 20, line 25 spanning pg. 21 line 7).
Regarding claim 38, Vallier teaches a biocompatible scaffold containing cholangiocytes (pg. 20, line 25 spanning pg. 21 line 7). Further, Chen teaches the isolated population of FXR-treated cholangiocytes, and in combination with the biocompatible scaffold of Vallier would provide a biocompatible scaffold containing the isolated population of FXR-treated cholangiocytes.
One of ordinary skill in the art would find it obvious at the effective filling date of the instant invention to combine the method of treating cholangiocytes with an FXR agonist taught by Chen with the method of expanding cholangiocytes taught by Vallier to arrive at the instant invention. One of ordinary skill in the art would be motivated to make this combination because Vallier teaches that the combination of a canonical Wnt signal inhibitor and a non-canonical Wnt/PCP signaling potentiator “unexpectedly allow the efficient expansion of primary cholangiocytes in the form of cholangiocyte organoids” (pg. 2, lines 5-9). One of ordinary skill in the art would have a reasonable expectation of success when combining Chen with Vallier because Vallier teaches a method of expansion of cholangiocytes which provides unexpected results and Chen provides a method of FXR agonist treatment which provides cholangiocytes which “possess key functionalities of primary cholangiocytes and display an adequate response to external stimuli” (Chen, Pg. 3, col. 2, para 1).
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the effective time of filing of the invention, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
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CONSTANTINA E. STAVROU
Examiner
Art Unit 1632
/TITILAYO MOLOYE/Primary Examiner, Art Unit 1632
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