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 with traverse of Group I, claims 1-8, 10-13, in the reply filed on 10/31/2025 is acknowledged. Claims 14-16, 18-20, 23-27, 29, 32-37, 39-43 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention.
The traversal is on the grounds that the groups I and III share the special technical feature as presently amended and that the prior art reference used in the restriction requirement to break unity no longer teaches the special technical feature (page 2, para 6).
This is not found persuasive because as indicated by the rejection below, the groups do not share the special technical feature which contributes over the prior art at the time the invention was made.
Applicants also argue that “the method claim 15 requires all the claim limitations of the method of claim 1 and only two further steps” such that “Performing a search for the two additional method steps would not be a burden on the Examiner” (page 3, para 3).
This is not found persuasive because the restriction requirement is based on lack of unity of invention under the PCT. As noted above, the groups do not share the special technical feature which contributes over the prior art at the time the invention was made.
The requirement is still deemed proper and is therefore made FINAL.
Claims status
Claims 46-48 is/are newly added. Claims 1-8, 10-13, 14-16, 18-20, 23-27, 29, 32-37, 39-43, 46-48 is/are currently pending with claims 14-16, 18-20, 23-27, 29, 32-37, 39-43 is/are withdrawn. Claims 1-8, 10-13, 46-48 is/are under examination.
Information Disclosure Statement
The listing of references in the specification, such as para [0213], is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because of the following informalities: Repetition of the same reference (WO2016141137A1) is noted in [0004].
Appropriate correction is required.
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. "Essential material" may be incorporated by reference, but only by way of an incorporation by reference to a U.S. patent or U.S. patent application publication, which patent or patent application publication does not itself incorporate such essential material by reference. 37 CFR 1.57(d). 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).
The specification references WO2016141137A1 in [0004], WO2015069619A1 and WO2016141137A1 in [0040] and Erikau (2008), WO2011/055855A1 in [0085]. These references are not deemed essential for the instant claims. However if the Applicant disagrees with this finding then Applicant is requested to follow the guidance above regarding essential material.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 12 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 12 recites culturing “at least two genetically-engineered inducible population of stem cells”. This is same as claim 1 and thus claim 12 does not further limit claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112(b)
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, 3, 46, 47 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.
Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). The term “stem cells” in claim 2 is used to mean “any cell” since it embraces cell types that are not stem cells such as progenitor cells, terminally differentiated cells, endothelial cells, endothelial progenitor cells, immortalized cell lines and primary cells; while the accepted meaning is “cells that are not terminally differentiated and retain at least a multi-potency i.e. ability to differentiate into more than one distinct cell type.” The term is indefinite because the specification does not clearly redefine the term.
Claim 3 recites a product-by-process limitation for generating the product of “genetically-engineered inducible populations of stem cells” of claim 1. The process is introducing “a DNA delivery element comprising at least one of constitutive promoter, small molecule inducible promoter, cell-autonomous promoter, cell non-autonomous promoter, selection marker or a combination thereof”. The specification defines “genetically-engineered inducible populations of stem cells” as “transgenic stem cells that contain inducible promoters to upregulate the expression of a set of specific genes, such as transcription factors, upon addition of an inducing agent” [0066]. It is unclear how the recited process step creates the stem cells of claim 1, especially when the DNA delivery element comprises non-inducible promoters such as recited in the claims. For the purpose of compact prosecution, the claim(s) 3 is/are interpreted as wherein the genetically-engineered inducible populations of stem cells further comprise a constitutive promoter, small molecule inducible promoter, cell-autonomous promoter, cell non-autonomous promoter, selection marker or a combination thereof introduced via a DNA delivery element.
Claim 46 recites the limitation "the at least one transcription factor" in line 2. There is insufficient antecedent basis for this limitation in the claim. Additionally, it is unclear what the inducing agent is acting on to overexpress the transcription factor. Additionally, it is unclear when the recited step is performed in relation to the culturing and differentiation steps of claim 1. For the purpose of compact prosecution, the claim(s) 46 is/are interpreted as wherein the inducing agent increases the activity of the inducible promoter in at least one of the genetically engineered inducible population of stem cells wherein the inducible promoter is operably linked to a transcription factor encoding sequence and the inducing agent is introduced during the culture and/or differentiation step. This interpretation is supported by the specification (Figure 2) and claim 48.
Claim 47 recites the limitation "the at least one transcription factor" in line 2. There is insufficient antecedent basis for this limitation in the claim. It is unclear what the inducing agent is acting on to overexpress the transcription factor. Additionally, it is unclear when the recited step is performed in relation to the culturing and differentiation steps of claim 1, specifically if the recited step is in addition to or an alternate to the differentiation step of claim 1. An interpretation similar to claim 46 is applied to claim 47 as well.
Claim Interpretation
Claim 1 is directed to a method of generating a programmable multicellular organoid and/or a 3D organ-specific tissue. The speciation defines “The term "a programmable multicellular organoid" refers to an organoid that is formed from multiple populations of human induced pluripotent stem cells (hiPSCs) that upregulate differing sets of transcription factors, such that they undergo orthogonally induced differentiation from a pluripotent tissue into a multicellular differentiated tissue.” [0043]. No definition for “3D organ-specific tissue” is provided and thus plain meaning of the term is used for claim interpretation - a 3D construct with multiple cell types (=tissue) that are specific to any organ. Although the definition for a programmable multicellular organoid requires the stem cells used in the method to be hiPSC that upregulate differing sets of transcription factors, such that they undergo orthogonally induced differentiation from a pluripotent tissue into a multicellular differentiated tissue, no such requirement is necessary for generation of 3D organ-specific tissue and thus no such requirement is necessary for the claimed method as a whole. This is evident from claim 2 that is not limited to hiPSC.
The claim comprises a step of culturing two genetically-engineered inducible population of stem cells and a step of concurrently inducing direct/trans-differentiation of the said stem cells into at least two divergent populations of cells.
The specification defines “genetically-engineered inducible populations of stem cells” as “transgenic stem cells that contain inducible promoters to upregulate the expression of a set of specific genes, such as transcription factors, upon addition of an inducing agent” [0066]. However, although the claimed genetically-engineered inducible populations of stem cells contain inducible promoter that regulates expression of a set of genes upon addition of an inducing agent, the claimed method does not recite addition of an inducing agent that activates the inducible promoter. Additionally the claim does not require that the activation of the inducible promoter in the claimed stem cells upregulate the expression of a set of specific genes, such as transcription factors, resulting in their direct/trans-differentiation.
Taken together, claim 1 comprises a step of culturing two genetically-engineered inducible population of stem cells and a step of concurrently inducing direct/trans-differentiation of the said stem cells into at least two divergent populations of cells, wherein the induction of direct/trans-differentiation of the said stem cells can occur by any means as long as a divergent populations of cells is generated.
Claim 3 recites “cell-autonomous promoter” and “cell non-autonomous promoter”. These are not terms in the art. The specification provides the following guidance: as an example of cell-autonomous promoters, the specification discloses “cell type-specific promoters” and as an example of cell non-autonomous promoters, the specification discloses “heat induced and light induced promoters” [0068]. Thus, cell-autonomous promoters are understood as promoters that are activated/inactivated based on the cell type itself whereas cell non-autonomous promoters are understood as promoters that are activated/inactivated by external stimuli.
Claim 4 requires the genetically-engineered inducible population of stem cells to overexpress a transcription factor. The claim does not require the transcription factor to be induced by an inducing agent and/or be operably linked to the inducible promoter of the said stem cells and/or be involved in direct/trans-differentiation of the said stem cells. Thus, claim 4 is broadly interpreted to require the genetically-engineered inducible population of stem cells to overexpress any transcription factor at any time during the method. Considering that expression levels of transcription factor fluctuate throughout a cell’s lifetime and especially during differentiation, this limitation is inherent to a stem cell undergoing differentiation. Thus, prior art that anticipates and/or renders obvious the method of claim 1, meets the limitation of claim 4.
Claim 6 requires addition or removal of various factors such as “small molecules, growth factors, dissolved gases, or morphogens” to induce direct/trans-differentiation of the genetically-engineered inducible population of stem cells. The claim does not require the recited factors to be an inducing agent that induce the activity of the inducible promoter of the said stem cells resulting in direct/trans-differentiation of the said stem cells. Thus, the recited factors embrace both an inducing agent that induce the activity of the inducible promoter of the said stem cells resulting in direct/trans-differentiation of the said stem cells and other factors that are known in the art to induce differentiation of stem cells, such as Wnt signaling modulators, SMAD modulators etc. This is also evident from claim 11 that also recites the same factors but for differentiation of wild-type cells i.e. not genetically engineered and thus not comprising an inducible promoter.
Claim 13 recites “wherein the method is used to enable”. The claim does not recite an active step rather is reciting an intended use of the method of claim 1. A prior art that anticipates and/or renders obvious the method of claim 1, is capable of the same use as the method of claim 1. Thus, prior art that anticipates and/or renders obvious the method of claim 1, meets the limitation of claim 13.
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.
Claim(s) 1-8, 10-13, 46-48 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ng, Hon Man Alex. April 2018. Differentiation of Human Cells and Tissues Using a Comprehensive Human Transcription Factor Library. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences. Publication date 2018-04-24
Regarding claims 1 and 12, Ng teaches a method for generating a multicellular cerebral organoid which is 3D brain-specific tissue (Chapter 3). The method comprises culturing unmodified i.e. wild type hiPSC with genetically-engineered hiPSCs that comprise a doxycycline-inducible endothelial transcription factor (Figure 3.1, 3.7; 3.3.7 Generation of stable vasculature within cerebral organoids; 3.5.9 Cerebral organoid culture.). The method further comprises inducing differentiation of the wild type hiPSC and the genetically-engineered hiPSCs concurrently by exposure to neural differentiation medium along with doxycycline which results in differentiation of wild type hiPSC into neural cells and differentiation of genetically-engineered hiPSCs comprising the doxycycline-inducible endothelial transcription factor into endothelial cells (Figure 3.1, 3.7; 3.3.7 Generation of stable vasculature within cerebral organoids; 3.5.9 Cerebral organoid culture.). The method, thus, results in differentiation of the wild type hiPSC and the genetically-engineered hiPSCs into divergent cells i.e. neural cells and endothelial cells thereby forming a multicellular organoid which is 3D brain-specific tissue that can be programmed by doxycycline.
Regarding claim 2, Ng teaches pluripotent stem cells (Figure 3.1, 3.7; 3.5.9 Cerebral organoid culture).
Regarding claim 3, Ng teaches genetically-engineered hiPSCs with inducible promoters introduced by lentivirus or Piggy-bac transposon (=DNA delivery element; 2.5.7 Lentiviral production and transduction.; 2.5.14 Nucleofection of PiggyBac and generation of stable cell lines.)
Regarding claim 4 and 5, Ng teaches ETV2, NGN1 transcription factors (page 16, 24).
Regarding claims 6-8, Ng teaches differentiation induction via neural induction medium comprising small molecules and growth factors and also via addition of doxycycline during culture (3.5.9 Cerebral organoid culture.).
Regarding claims 10 and 11, Ng teaches culturing wild type hiPSC and inducing their differentiation into neural cells by addition of neural induction medium comprising small molecules and growth factors (3.5.9 Cerebral organoid culture.).
Regarding claim 13, in view of claim interpretation presented above, Ng renders obvious the method of claim 1 and thus meets its intended use. Additionally, Ng teaches inclusion of additional cell types in the organoid (page 69, 70).
Regarding claim 46, Ng teaches adding doxycycline as an inducing agent to induce over expression of a transcription factor, ETV2, in one of the genetically-engineered inducible hiPSC (Figure 3.1, 3.7; 3.3.7 Generation of stable vasculature within cerebral organoids; 3.5.9 Cerebral organoid culture).
Regarding claim 47, Ng teaches adding doxycycline as an inducing agent to induce over expression of a transcription factor, ETV2, in one of the genetically-engineered inducible hiPSC to concurrently induce differentiation of the wild type hiPSC and the genetically-engineered hiPSCs into divergent cells i.e. neural cells and endothelial cells (Figure 3.1, 3.7; 3.3.7 Generation of stable vasculature within cerebral organoids; 3.5.9 Cerebral organoid culture).
Regarding claim 48, Ng teaches a method for generating a multicellular cerebral organoid which is 3D brain-specific tissue (Chapter 3). The method comprises culturing unmodified i.e. wild type hiPSC with genetically-engineered hiPSCs that comprise a doxycycline-inducible endothelial transcription factor (= step (i) in part; Figure 3.1, 3.7; 3.3.7 Generation of stable vasculature within cerebral organoids; 3.5.9 Cerebral organoid culture.). The method further comprises adding doxycycline as an inducing agent to induce over expression of a transcription factor, ETV2, in one of the genetically-engineered inducible hiPSC to concurrently induce differentiation of the wild type hiPSC and the genetically-engineered hiPSCs into divergent cells i.e. neural cells and endothelial cells (= step (ii); Figure 3.1, 3.7; 3.3.7 Generation of stable vasculature within cerebral organoids; 3.5.9 Cerebral organoid culture.). The method, thus results in differentiation of the wild type hiPSC and the genetically-engineered hiPSCs into divergent cells i.e. neural cells and endothelial cells thereby forming a multicellular organoid which is 3D brain-specific tissue that can be programmed by doxycycline (= iii).
Ng generated their cerebral organoid by mixing wild type hiPSC and the genetically-engineered inducible hiPSCs and not two genetically-engineered inducible hiPSCs as required by claims 1 and 48.
However, Ng provides teaching, suggestion and motivation to include more than one genetically-engineered inducible hiPSCs in organoids.
Ng identifies transcription factors that can induce differentiation in stem cells without need for additional differentiation inducing factors (Figure 2.3D; 2.3.3 A pooled, FACS-based TFome screen reveals hundreds of TFs can induce loss of pluripotency) and validate some of these identified transcription factor in hiPSC by generating genetically-engineered hiPSCs comprising the doxycycline-inducible transcription factors (2.3.5 Validation of hits reveal diverse morphologies). They teach “ATOH1 and NEUROG3-induced cells appeared to exhibit neurites similar to neuronal cells. NKX3.2 and ETV2-induced cells had large, flatten morphologies. However they were subtly different, as ETV2 cells appeared to be space-filling whereas NKX3.2 cells were larger and in contact with each other. FOXC1, SOX14, HOXB6, ZSCAN1 and MITF appeared flat with comparatively smaller size” (page 24, last para; Figure 2.5; 2.3.7 NKX3-2 induces stromal fibroblast-like cells; 2.3.8 NEUROG3 induces neuronal differentiation; 3.3.2 A splice isoform of ETV2 induces potent endothelial differentiation). Critically, they teach that this ability of certain transcription factors to rapidly induce differentiation in stem cells, without any need of external differentiation factors, was already known based on prior work from their lab showing “based on our previous work using NEUROG1/2 to induce neuronal differentiation with >90% efficiency in only four days in pluripotency-maintaining conditions (28), we hypothesized the existence of other TFs that are equally potent at differentiating cells under the same conditions” (page 16, para 1; 1.3 Transcription factors for cell conversion).
Ng teaches several genetically-engineered hiPSCs with inducible promoters operably linked to transcription factors that upon induction differentiate the hiPSC into other cell types. For example, in addition to hiPSCs with doxycycline-inducible endothelial transcription factor, Ng also teaches genetically-engineered hiPSCs with doxycycline-inducible neural transcription factor and genetically-engineered hiPSCs with doxycycline-inducible stromal transcription factor (2.3.7 NKX3-2 induces stromal fibroblast-like cells; 2.3.8 NEUROG3 induces neuronal differentiation; 3.3.2 A splice isoform of ETV2 induces potent endothelial differentiation).
Furthermore, Ng teaches “the ability to induce alternative cell fates within the same media conditions using genetic components could enable sophisticated genetic circuits that carefully guide organoid development. This approach may be used to incorporate additional missing cell types,” (page 69) and “With this strategy, we can incorporate additional cell types to organoids and control their timing. Additional modes of control would be ideal: orthogonal inducible or conditional promoters would allow additional cell types to be differentiated separately, rather than all at once under doxycycline control” (page 70).
Taken together, Ng provides teachings regarding various hiPSCs with doxycycline-inducible transcription factors and their use in organoids. Ng also suggests that organoids with several cell types could be combined and induced to differentiate into divergent cell types based on the inducible genetic components.
Therefore, it would be obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine more than one genetically-engineered inducible hiPSCs in the method to produce an programmable multicellular organoid, as taught by Ng. An ordinary artisan would be motivated to combine more than one genetically-engineered inducible hiPSCs in an organoid because it would allow for precise spatial and/or temporal control of hiPSC differentiation into divergent cell types based on exposure to the inducing agent resulting in a more controlled organoid. An ordinary artisan would reasonably expect to combine more than one genetically-engineered inducible hiPSCs in an organoid because Ng teaches various hiPSC with inducible promoters that drive transcription factors that rapidly differentiate the hiPSCs into distinct cells without need for any additional elements and also teaches the use of an hiPSC with inducible promoters that drive transcription factors in an organoid.
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.
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 conflicting claims 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); 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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) 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 www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-4, 6-8, 10, 11, 12, 13, 46, 47, 48 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 24, 26-28, 30, 31 of U.S. Patent No. 11,214,768 in view of Ng, Hon Man Alex. April 2018. Differentiation of Human Cells and Tissues Using a Comprehensive Human Transcription Factor Library. Doctoral dissertation, Harvard University, Graduate School of Arts & Sciences. Publication date 2018-04-24.
Regarding instant claim 1, 12, Claim 24 of `768 is directed to a method of generating a functional human tissue wherein the tissue comprises organoids produced by the steps recited in claim 24. The steps recites are culturing a wild type population of cells and a genetically-engineered inducible population of cells and then inducing differentiation of the genetically-engineered inducible population of cells into a first organoid cells and differentiating the wild-type cells into a second organoid cells. Thus, the method of `768 produces a multicellular organoid that is programmable due to the presence of the genetically-engineered inducible population of cells.
Regarding instant claim 2, Claim 27, 31 of `768 identifies the cells as pluripotent stem cells.
Regarding instant claim 3, 4, Claim 26 of `768 identifies promoters comprised in the genetically-engineered inducible population of cells.
Regarding instant claims 6-8, claims 28, 30 of `768 identify use of inducing agent such as doxycycline.
Regarding instant claim 10, Claim 24 of `768 teach a wild type population of cells that are differentiated into a first organoid cells.
Regarding instant claims 46-48, claim 28 and 30 of `768 teach introducing an inducing agent to induce differentiation.
Claims of `768 does not teach culturing two genetically-engineered inducible population of cells.
Ng teaches various hiPSCs with doxycycline-inducible transcription factors and their use in organoids (page 24, last para; Figure 2.5; 2.3.7 NKX3-2 induces stromal fibroblast-like cells; 2.3.8 NEUROG3 induces neuronal differentiation; 3.3.2 A splice isoform of ETV2 induces potent endothelial differentiation; Figure 3.1, 3.7; 3.3.7 Generation of stable vasculature within cerebral organoids; 3.5.9 Cerebral organoid culture). Ng also suggests that organoids with several cell types could be combined and induced to differentiate into divergent cell types based on the inducible genetic components (page 16, 69, 70).
Therefore, it would be obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention to combine more than one genetically-engineered inducible hiPSCs, taught by Ng, in the method to produce an programmable multicellular organoid, as taught by `768. An ordinary artisan would be motivated to combine more than one genetically-engineered inducible hiPSCs in an organoid because it would allow for precise spatial and/or temporal control of hiPSC differentiation into divergent cell types based on exposure to the inducing agent resulting in a more controlled organoid, based on teachings from Ng. An ordinary artisan would reasonably expect to combine more than one genetically-engineered inducible hiPSCs in an organoid because Ng teaches various hiPSC with inducible promoters that induce rapidly differentiation of hiPSCs into distinct cells and `768 teaches the use of an hiPSC with inducible promoters that drive differentiation of hiPSC in an organoid.
Conclusion
No claim is allowed.
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/MATASHA DHAR/Examiner, Art Unit 1632