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 .
Clams 4, 8, 11, 14, 17, 19, 21-22, 29-57 have been canceled, and claims 1-3, 5-7, 9-10, 12-13, 15-16, 18, 20 and 23-28 have been considered on the merits.
Priority
The earliest filing date of the instant application is the filing date of 63/349,205, which is 6/6/2022.
Specification
The use of the term “Matrigel” (p.5 of the specification), 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 § 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 1-3, 5-7, 9-10, 12-13, 15-16, 18, 20 and 23-28 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 1 discloses a method for generating lung progenitor cells comprising the steps (a)-(d). However, claim 1 does not particularly indicate whether or not the dissociated LBO or BLBO in step (d) and the culturing would produce the lung progenitor cells or there is any additional steps in order to generate the claimed cells. In fact, it appears that after step (c), the cells obtained would be also considered lung progenitor cells. The lung progenitor cells would be also generated after step (b) because the specification discloses that the lung progenitor cells may be in the form of lung organoids. Clarification is required.
The language of a claim must make it clear what subject matter the claim encompasses to adequately delineate its "metes and bounds". See, e.g., the following decisions: In re Hammack, 427 F 2d. 1378, 1382, 166 USPQ 204, 208 (CCPA 1970); In re Venezia 530 F 2d. 956, 958, 189 USPQ 149, 151 (CCPA 1976); In re Goffe, 526 F 2d. 1393, 1397, 188 USPQ 131, 135 (CCPA 1975); In re Watson, 517 F 2d. 465, 477, 186 USPQ 11, 20 (CCPA 1975); In re Knowlton 481 F 2d. 1357, 1366, 178 USPQ 486, 492 (CCPA 1973).
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.
Claim(s) 1-3, 5-7, 9, 12-13, 15-16, 18, 20, 23-28 is/are rejected under 35 U.S.C. 103 as being unpatentable over Snoeck et al. (US2021/0115408A1; IDS ref.) in view of Hawkins et al. (US2021/0254016A1; IDS ref.) and Schmeckebier et al. (2013, Tissue Engineering).
Regarding claim 1, Snoeck et al. teach a method for generating lung progenitor cells comprising the steps of (a) producing anterior foregut endoderm cells from mammalian pluripotent stem cells (PSCs); (b) culturing the anterior foregut endoderm cells in a suspension culture to generate at least one lung bud organoid (LBO); ( c) embedding the LBO within a 3D matrix; (d) culturing the embedded LBO to form branched LBO (BLBO), and (e) dissociating the LBO or BLBO and culturing the dissociated LBO or BLBO on feeder cells in a culture medium (para. 12).
While the steps (a), (b), (c) and (d) are identical to the claimed steps, however, step (e) of Snoeck et al. does not teach the use of 3D matrix required by the claimed step (d), rather they use feeder cells instead. However, the feeder cells of Snoeck et al. are broadly interpreted as a 3D matrix. Because the feeder cells would inherently secrete the matrix proteins, and thus, forming a 3D matrix. Even if the feeder cells for step (e) are not considered as a 3D matrix, however, it is well known in the art that lung progenitor cells can be cultured in a 3D matrix as shown in step (c) of Snoeck et al. Furthermore, Snoeck et al. teach that the dissociated cells from the organoids (i.e. LBO or BLBO) at various stages of development can be cultured in the presence of a ROCK inhibitor (e.g., Y27632) and growth factors (e.g., the same growth factor combination that drives the development of branching organoids in Matrigel, such as the GSK3 inhibitor CHIR99021, FGF7, FGFl0, retinoic acid and BMP4) (para. 94). This teaching is understood the same as step (d) of the claimed invention. While Snoeck et al. utilize feeder cells for the step (e), one skilled in the art would recognize that a 3D matrix such as Matrigel would be also utilized for the step (e) with a reasonable expectation of success.
Regarding the step (b) directed to the GSK inhibitor, a BMP agonist, a FGF agonist, and retinoic acid (claim 1) and GSK inhibitor’s concentration (claims 2-3), Snoeck et al. teach that the culture medium comprises a GSK inhibitor including CHIR99021 (para. 15) at about 1 mM or about 10 mM (para. 16), and one or more of FGF7, FGF10 (FGF agonist), BMP4 (i.e. BMP agonist) and retinoic acid (para. 17).
Regarding the step (d) directed to the culturing the dissociated LBO or BLBO in a 3D matrix in presence of a GSK3 inhibitor, an FGF agonist, a corticosteroid, a cAMP activator and a PDE inhibitor, while Snoeck et al. teach the use of a GSK3 inhibitor and an FGF agonist, however, they do not teach the corticosteroid, cAMP activator and the PDE inhibitor.
Hawkins et al. teach NKX2-1+ lung progenitors are cultured in the presence of dexamethasone, 8-bromoadenosine 3’,5’-cyclic monophosphate sodium salt (cAMP), 3-isobutyl-1-methylxanthine to drive airway program and to form airway organoid containing airway progenitors (IBMX; PDE inhibitor) (para. 181-183, 287).
Schmeckebier et al. teach that KGF, dexamethasone (corticosteroid), 8-bromoadenosine-cAMP (cAMP activator) and isobutylmethylxanthine (i.e. PDE inhibitor) synergistically support the differentiation of pluripotent stem cells into alveolar epithelial type II cells (Abstract), and the method of Schmeckebier et al. would produce lung progenitor cells (i.e. Nkx2.1 pos progenitor) differentiated from the PSCs, and ATII cells act as progenitor cells for ATI cells, thus being able to renew the alveolar epithelium (p.939, 1st col.).
It would have been obvious to a person skilled in the art to use the factors taught by Hawkins et al. and Schmeckebier et al. including cAMP, a corticosteroid (dexamethasone) and a PDE inhibitor (IBMX) for the method of Snoeck et al. with a reasonable expectation of success.
Regarding claims 5-7 directed to FGF10 and KGF, Snoeck et al. teach FGF7 and FGF10 (para. 17), and FGF7 is known as keratinocyte growth factor. Snoeck et al. teach the concentration of the FGF agonist, i.e. FGF7 and FGF10 are about 10 ng/ml (para. 17).
Regarding claim 9, the combined teachings of Snoeck et al. in view of Hawkins et al. and Schmeckebier et al. disclose dexamethasone (see above).
Regarding claim 12, Hawkins et al. and Schmeckebier et al. both teach 8-bromo-cAMP (see above).
Regarding claim 13 directed to the concentration of 8-bromo-cAMP being 0.05-0.2 mM, Schmeckebier et al. teach the concentration of 8-bromo-cAMP is 0.1 mM (p.939, 2nd col.; Materials and Methods). Thus, it would have been obvious to a person skilled in the art to use 0.1 mM of 8-bromo-cAMP for the method of Snoeck et al. in view of Hawkins et al. and Schmeckebier et al. with a reasonable expectation of success because 0.1 mM 8-bromo-cAMP is utilized for the method of generating lung progenitors according to Schmeckebier et al.
Regarding claim 15-16, Schmeckebier et al. teach the use of IBMX at 0.1 mM (p.939, 2nd col.; Materials and Methods). Thus, it would have been obvious to a person skilled in the art to use 0.2 mM of IBMX for the method of Snoeck et al. in view of Hawkins et al. and Schmeckebier et al. with a reasonable expectation of success because 0.2 mM IBMX is utilized for the method of generating lung progenitors according to Schmeckebier et al.
Regarding claim 18 directed to the BMP4, as discussed above, Snoeck et al. teach the use of BMP4 for the method (para. 17).
Regarding claim 20 directed to the concentration of retinoic acid being about 50 nM, Snoeck et al. teach the concentration of retinoic acid is about 50 nM (para. 17).
Regarding claims 23-25 directed to the types of lung progenitor cells generated by the method of claim 1, Snoeck et al. teach that the cells from the lung bud organoids would become “lung progenitor cells” or “basal cell-like” (para. 147), however, neither Snoeck et al. nor Hawkins et al. and Schmeckebier et al. do not teach all the claimed cell types of the lung progenitor cells listed in the claims obtained by the method. However, as the method steps of Snoeck et al. in view of Hawkins et al. and Schmeckebier et al. are identical to the claimed method steps of claim 1 as discussed above, the results obtainable from the method, i.e. types of lung progenitor cells generated by the claimed method, would be expected the same.
Regarding claim 26 directed to the LBO comprising lung epithelial cells expressing FOXA2, FOXA1, NKX2.1 and EPCAM and mesenchymal progenitor cells expressing PDGFRa, CD90, TBX4 and HOXA5, Snoeck et al. teach that lung bud organoid(s) (LBO(s)) may be derived from pluripotent stem cells ( e.g., human pluripotent stem cells) in suspension and contain lung epithelial (expressing FOXA2, FOXAl, NKX2.1 and EPCAM) and/or mesenchymal progenitors (expressing PDGFRa, CD90, TBX4, and HOXA5) (para. 136).
Regarding claim 27, Snoeck et al. teach that the 3D matrix comprises a gelatinous extracellular protein mixture secreted by Engelbreth-Holm -Swarm (EHS) mouse sarcoma cells (para. 83).
Regarding claim 28 directed to the mammalian PSCs being human, Snoeck et al. teach human PSCs (hPSCs) (para.24).
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Claim(s) 10 is/are rejected under 35 U.S.C. 103 as being unpatentable over Snoeck et al. in view of Hawkins et al. and Schmeckebier et al. as applied to claim 1 above, and further in view of Osafune et al. (US20160068816A1).
Regarding claim 10 directed to the concentration of dexamethasone, Hawkins et al. teach 50 nM (para. 287) and Schmeckebier et al. teach 10 nM of dexamethasone. However, they do not teach the claimed range of 100-150 nM.
Osafune et al. teach a method of producing alveolar epithelial progenitor cells from pluripotent stem cells (Abstract), and the method utilizes dexamethasone along with 8Br-cAMP and IBMX (para. 10, step [13]). Osafune et al. teach that the concentration of dexamethasone can be 1 nM up to 1 mM, including 100 nM (para. 88).
It would have been obvious to a person skilled in the art to use 100 nM dexamethasone for the method of Snoeck et al. in view of Hawkins et al. and Schmeckebier et al. A person of ordinary skill in the art would have been motivated to do so because 100 nM dexamethasone taught by Osafune et al. is for the same purpose as the method of Snoeck et al. in view of Hawkins et al. and Schmeckebier et al.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the effective filing date of the claimed invention.
Conclusion
No claims are allowed.
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/TAEYOON KIM/ Primary Examiner, Art Unit 1631
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