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
Claims 10-17, 34, 35, 39-42 and 46 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected group, there being no allowable generic or linking claim.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 1/9/2026.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The incorporation of essential material in the specification by reference to an unpublished U.S. application, foreign application or patent, or to a publication is improper. Applicant is required to amend the disclosure to include the material incorporated by reference, if the material is relied upon to overcome any objection, rejection, or other requirement imposed by the Office. The amendment must be accompanied by a statement executed by the applicant, or a practitioner representing the applicant, stating that the material being inserted is the material previously incorporated by reference and that the amendment contains no new matter. 37 CFR 1.57(g).
Claim Rejections - 35 USC § 112
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 2 and 4 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.
Claim 2 is indefinite because it is unclear what the source of the claimed cells is. The parent claim (claim 1) provides for “hepatic-derived cells,” and based upon the general accepted definition of the term “derived,” this would suggest that the origin of these cells is from the liver. Claim 2 provides for indefiniteness because it further defines the hepatic-derived cells as “adult stem-cell derived” or “induced pluripotent derived stem cells.;” This is indefinite because it suggests that the cells which must be sourced from the liver (hepatic-derived) must be source somewhere that is not the liver; that is to say, the limitation makes the source of the cells unclear, since the dictionary and biological definition for “derived” would be interpreted to mean “originated.” For the sake of examining the claim on its merit, it will be assumed that the stem cells of claim 2 are induced into a hepatic lineage; however, this interpretation suggests a product-by-process limitation, wherein the claim requires that the hepatic cells of claim 1 are generated by a method of inducing the stem cells of claim 2. Based upon this interpretation, there is no clear distinction between hepatic-derived cells and cells induced to appear hepatic-derived, and as such, barring evidence to the contrary, they can be assumed to be the same. See MPEP 2113.
Claim 4 recites the limitation "the organ’s three-dimensional structures" in the second line. There is insufficient antecedent basis for this limitation in the claim. Although it is noted that the parent claim provides for “organ-like functionality,” claim 4 describes an anatomical limitation that was not described in the parent claim, whereas the limitation “organ-like functionality” is only drawn to the organoid’s physiology. Since there is nothing in the parent claim regarding and fine “structures,” three-dimensional or otherwise, there is no antecedent support for the limitation.
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.
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, 2 and 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Nantasanti, et al (Stem Cell Reports, 5, 895-907, 2015 [IDS Reference]) Groba, et al (Metallomics, 9, 1279-1287, 2017) and Lin, et al (Clinical Pharmacokinetics, 42, 59-98, 2003). Nantasanti teaches a canine hepatic organoid that is derived from hepatic cells. See page 904, “Experimental Procedures” section. Nantasanti’s canine hepatic organoid possesses organ-like functionality. See page 895, “Abstract” section. Nantasanti alters the expression of the COMMD1 gene, Nantasanti does not alter the expression of P-glycoprotein.
Groba provides for methods of downregulating MDR1, which controls P-glycoprotein expression, by inserting a vector into hepatic-derived cells. See page 1279, “Abstract” section. Groba does not teach controlling P-glycoprotein in an organoid.
Lin provides a review paper regarding the importance of P-glycoprotein in pharmacokinetics. Specifically, Lin notes how this protein affects the efflux and metabolism of pharmaceuticals in the hepatic space. The content of Lin is used to provide a general idea of the state-of-the-art regarding P-glycoprotein regulation in hepatic cells, and implicit motivations that the ordinary artisan would find obvious, even if it is not stated in the other prior art used to reject the claims.
Nantasanti describes the canine hepatic organoid as a disease model. See page 896, left column, first [full] paragraph. This would suggest to the ordinary artisan that the organoid can be modified in a number of ways in order to elicit certain disease types and other physiological effects. Since the ordinary artisan possesses ample academic and applied knowledge in the instant field, there would be reasonable motivation for the ordinary artisan to modify Nantasanti so that it can model other diseases, pharmaceutical metabolism and excretion, and other physiological states. See MPEP 2141.03. Lin shows what the ordinary artisan would be aware of, with respect to P-glycoprotein, and indicates its clear importance regarding pharmacokinetic modeling when the P-glycoprotein gene is knocked out. See page 69, left column, first [full] paragraph; page 78, right column; page 80 and 81, “Drug metabolism” section; page 81, “Drug Excretion” section. Lin also shows examples of P-glycoprotein upregulation, and motivation to apply some form of knock-in gene. See page 88, “P-Glycoprotein Induction is a Complex Process” section.
With respect to claim 1, Nantasanti teaches the claimed canine hepatic-derived organoid. Groba and Lin provide motivation to modify the P-glycoprotein of the organoid.
With respect to claim 2, the claim is interpreted (see the 35 USC 112(b) rejection of this claim) as being a hepatic organoid, wherein the hepatic cells were derived from adult or induced pluripotent stem cells. This limitation is interpreted as a product-by-process limitation, wherein the hepatic cells are derived from a method of inducing the aforementioned stem cells. See MPEP 2113. Since hepatic cells derived from stem cells should appear and behave identical to their naturally-occurring counterparts, the claim describes cells that must be either the same or obvious variants of the hepatic cells in Nantasanti. Barring evidence to the contrary, the claimed cells are assumed to be identical to the hepatic cells of Nantasanti.
With respect to claim 4, Nantasanti describes that the cells are cultured in Matrigel, which is an extracellular matrix derived from the basement membrane of mouse sarcoma cells. See page 904, “Hepatocyte Differentiation” section.
With respect to claim 5, Nantasanti shows epithelial cells that express tight junction proteins. See page 899, right column, first [incomplete] paragraph.
With respect to claim 6, both Groba and Lin describe P-glycoprotein downregulation.
Claim 7 is rejected under 35 U.S.C. 103 as being unpatentable over Nantasanti, et al (Stem Cell Reports, 5, 895-907, 2015 [IDS Reference]) Groba, et al (Metallomics, 9, 1279-1287, 2017) Lin, et al (Clinical Pharmacokinetics, 42, 59-98, 2003) and Borst, et al (The Journal of Clinical Investigations, 123, 4131-4133, 2013) Although both Groba and Lin indicate that the P-glycoprotein functionality is linked to an ABC transporter, there is nothing in either reference that suggests mutating the ABCB1-1Δ gene. However, it would be obvious to the ordinary artisan to mutate any gene that would affect P-glycoprotein expression, if the intent is to up- or downregulate the expression of P-glycoprotein. This assessment is underscored by Borst, who notes that P-glycoprotein expression can be affected by inserting a mutant ABCB1-1Δ gene. See page 4131, “Abstract” section.
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.
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/DAVID W BERKE-SCHLESSEL/ Primary Examiner, Art Unit 1651