DETAILED ACTION
Claims 15-34 from the claim set filed 5/17/2024 are pending. Claims 1-14 are cancelled. Claims 17 and 26-34 are withdrawn. Thus, examination on the merits commences for claims 15-16 and 18-25.
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
Applicants’ election without traverse of Group I, claims 15-25, drawn to a method for culturing monoclonal cells derived from salivary gland epithelial stem cells or progenitor cells, in the reply filed 8/5/2026 is acknowledged. Applicants’ election of LDN193189 as the species of BMP inhibitor, i.e., claim 16, is acknowledged. Thus, claims 17 and 26-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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 15-16 and 18-25 will be examined on the merits herein.
Priority
A claim for benefit of a prior-filed application under 35 U.S.C. 119(a)-(f) or under 35
U.S.C. 120, 121, 365(a)-(c), 386 (a) or 386(c) has been made. The effective filing date of the
present application is 11/19/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 5/17/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings are objected to because the character of the letters and numbers is poor in many of the figures causing the writing to be illegible. Examiner notes Figures 1, 2, 3, 5, 7, 10,13, 14, 16, 18 are particularly hard to read.
See 37 CFR 1.84(l)
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 102(a)(1) &102(a)(2)
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 15, 19-20, and 22-25 are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by McKeon (US2024/0158756 A1, published May 16, 2024, EFD October 10, 2019; PTO 892).
In regards to claim 15, McKeon teaches a culture media system that is useful for the isolation and epigenetically stable propagation of stem cells in culture, wherein the stem cells are derived from stratified epithelial tissues (Abstract). McKeon teaches cloned human epithelial stem cells derived from salivary gland [0084]. Further, McKeon teaches single, i.e., monoclonal, human salivary gland stem cell culturing ([0084], Fig 10).
McKeon teaches the invention provides a method for isolating a stem cell from epithelial tissue, preferably stratified epithelial tissue [0009]. McKeon teaches obtaining human salivary gland tissues to obtain salivary gland epithelial stem cells ([0084], Fig 10) (i.e., step 1 of claim 15).
McKeon teaches a defined culture medium for isolating (i.e., step 2 of claim 15) and stably maintaining the epigenetics of stratified epithelial stem cells through a plurality of passaging in culture (i.e., step 3 of claim 15), the medium comprising: …, a ROCK inhibitor, …, a TGFß inhibitor, and a BMP antagonist (i.e., inhibitor), wherein the culture media supports the epigenetically stable growth and proliferation of stem cells of stratified epithelial tissue origin in culture (claim 1, p103).
McKeon teaches culturing the dissociated salivary gland epithelial stem cells to form stem cell colonies, wherein the dissociated cells and cell colonies are cultured in a medium comprising [0011]; a ROCK inhibitor [0012], a TGFß inhibitor [0014], and a BMP inhibitor [0015], [0173]. McKeon teaches said culturing as step (1). McKeon teaches the ROCK inhibitor may be Y-27632 [0033] and the TGFß inhibitor may be A83-01 [0037].
McKeon teaches isolating single stem cells from the cell colonies [0020]. McKeon teaches said isolation as step (2). McKeon teaches culturing said isolated single stem cells from step (2) individually to form cultures of purified stem cell clones, i.e., monoclonal cells [0021]. McKeon teaches said culturing as step (3). McKeon teaches culturing in the same defined media as defined by claim 1, which as noted supra comprises: …, a ROCK inhibitor, …, a TGFß inhibitor, and a BMP antagonist (i.e., inhibitor) (claim 2).
McKeon teaches an object of the present invention is to provide systems and reagents for the rapid isolation/cloning of stratified epithelial stem cells, i.e., of which salivary gland epithelial stem cells are an example, particularly from small biopsies, under conditions which preserve the epigenetic memory and faithfully preserves the in vivo characteristics of the stem cells as they existed in the tissue biopsy through rounds of expansion and passaging in culture, so as to be scalable, efficient and ultimately affordable enough to be done on a patient-by-patient process for patient specific diagnostic and treatment strategy purposes or regenerative medicine purposes [0009].
Thus, McKeon anticipates claim 15.
In regards to claim 19, McKeon teaches the Rock inhibitor (i.e., Y-27632) final concentration is about 1-5µM, or 2.5µM [0154]. It is noted the range disclosed by McKeon is disclosed with sufficient specificity to constitute an anticipation. See MPEP 2131.03(II)
In regards to claim 20, McKeon teaches the TGFß signaling inhibitor (i.e., A83-01) is added at a concentration of between 100nM and 10 µM, or approximately 1 µM [0039]. Thus, the range of McKeon falls within the claimed range. It is noted the range disclosed by McKeon is disclosed with sufficient specificity to constitute an anticipation. See MPEP 2131.03(II)
In regards to claim 22, McKeon teaches wherein in step (2) of the instant application, WNT3A is added to the culture medium [0016], [0161].
In regards to claim 23, Examiner notes the limitation “wherein the monoclonal cells derived from salivary gland epithelial stem cells or progenitor cells are CD49f+/CD26- salivary gland basal cells”, is a wherein statement that is directed to an intended result. It is noted that as indicated in MPEP § 2111.04, a wherein clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.
As discussed supra, McKeon teaches the same method steps of obtaining/isolating/culturing monoclonal cells derived from salivary gland epithelial stem cells as disclosed in the instant application. Thus, because the cells are produced by the same method, it therefore stands to reason that the produced cell population must inherently be the same.
Under the principles of inherency, if a prior art method, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered to be anticipated by the prior art method. When the prior art method is the same as the method described in the instant application for carrying out the claimed method, it can be assumed the method will inherently perform the claimed process and produce the identical or substantially identical product. See In re Best, 562 F. 2d, 1252, 1255, 195 USPQ 430, 433 (CCPA 1977) and Ex parte Novitski, 26 USPQ 2d 1389 (Bd. Pat. App. & inter. 1993). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of the invention, but only that the subject matter is in fact inherent in the prior art reference. See Schering Corp. v. Geneva Pharm. Inc, 339 F.3d 1373, 1377, 67, USPQ2d 1664, 1668 (Fed. Cir. 2003). See also Toro Co. v. Deere & Co. 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004). MPEP 2112.01
In regards to claim 24, McKeon teaches wherein the monoclonal cells derived from salivary gland epithelial stem cells express KRT5 [0084]. Examiner notes however, the limitation “wherein the monoclonal cells derived from salivary gland epithelial stem cells or progenitor cells express any one or more selected from KRT14, KRT5, KRT19, SOX9, TP63, and CDH1”, is a wherein statement that is directed to an intended result. It is noted that as indicated in MPEP § 2111.04, a wherein clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.
As discussed supra, McKeon teaches the same method steps of obtaining/isolating/culturing monoclonal cells derived from salivary gland epithelial stem cells as disclosed in the instant application. Thus, because the cells are produced by the same method, it therefore stands to reason that the produced cell population must inherently be the same.
Under the principles of inherency, if a prior art method, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered to be anticipated by the prior art method. When the prior art method is the same as the method described in the instant application for carrying out the claimed method, it can be assumed the method will inherently perform the claimed process and produce the identical or substantially identical product. See In re Best, 562 F. 2d, 1252, 1255, 195 USPQ 430, 433 (CCPA 1977) and Ex parte Novitski, 26 USPQ 2d 1389 (Bd. Pat. App. & inter. 1993). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of the invention, but only that the subject matter is in fact inherent in the prior art reference. See Schering Corp. v. Geneva Pharm. Inc, 339 F.3d 1373, 1377, 67, USPQ2d 1664, 1668 (Fed. Cir. 2003). See also Toro Co. v. Deere & Co. 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004). MPEP 2112.01
In regards to claim 25, Examiner notes the limitation “wherein the monoclonal cells derived from salivary gland epithelial stem cells or progenitor cells have multipotency into salivary gland epithelial tissue” is a wherein statement that is directed to an intended result. It is noted that as indicated in MPEP § 2111.04, a wherein clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.
As discussed supra, McKeon teaches the same method steps of obtaining/isolating/culturing monoclonal cells derived from salivary gland epithelial stem cells as disclosed in the instant application. Thus, because the cells are produced by the same method, it therefore stands to reason that the produced cell population must inherently be the same.
Under the principles of inherency, if a prior art method, in its normal and usual operation, would necessarily perform the method claimed, then the method claimed will be considered to be anticipated by the prior art method. When the prior art method is the same as the method described in the instant application for carrying out the claimed method, it can be assumed the method will inherently perform the claimed process and produce the identical or substantially identical product. See In re Best, 562 F. 2d, 1252, 1255, 195 USPQ 430, 433 (CCPA 1977) and Ex parte Novitski, 26 USPQ 2d 1389 (Bd. Pat. App. & inter. 1993). There is no requirement that a person of ordinary skill in the art would have recognized the inherent disclosure at the time of the invention, but only that the subject matter is in fact inherent in the prior art reference. See Schering Corp. v. Geneva Pharm. Inc, 339 F.3d 1373, 1377, 67, USPQ2d 1664, 1668 (Fed. Cir. 2003). See also Toro Co. v. Deere & Co. 355 F.3d 1313, 1320, 69 USPQ2d 1584, 1590 (Fed. Cir. 2004). MPEP 2112.01
Thus, McKeon anticipates claims 15, 19-20, and 22-25 and therefore said claims are properly rejected.
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.
Claims 16 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over McKeon in view of StemMACS (StemMACS (copyright 2020), retrieved from the internet 9/22/2026, file:///C:/Users/ksmall/Downloads/StemMACS%E2%84%A2%20LDN-193189%20(1).pdf; PTO 892).
In regards to claims 16 and 18, as discussed supra, McKeon teaches BMP inhibitors. McKeon does not teach LDN193189. McKeon teaches a BMP inhibitor as used herein includes an agent that inhibits BMP signaling through its receptors [0174] and teaches the BMP inhibitor may include an agent that acts as an antagonist [0175]. McKeon teaches Noggin [0177].
StemMACS teaches LDN193189 is a highly potent, selective, and cell permeable inhibitor of BMP signaling. StemMACS teaches LDN193189 inhibits BMP type I receptors. StemMACS teaches LDN193189 is a derivative of dorsomorphin and has been used instead of the protein Noggin for inhibition of BMP signaling (p1, 1.1).
Therefore, it would have been obvious to a POSITA, before the effective filing date of the claimed invention, to make a simple substitution of one known element for another to obtain predictable results. It would have been obvious to substitute the BMP inhibitor Noggin, as taught by McKeon, for the BMP inhibitor LDN193189, as taught by StemMACS. The skilled artisan would have had a reasonable expectation of successfully substituting said BMP inhibitors as StemMACS teaches LDN193189 has been used instead of Noggin for inhibition of BMP signaling. Substitution of one element for another known in the field is considered to be obvious, absent a showing that the result of the substitution yields more than predictable results. See KSR International Co. v Teleflex Inc 82 USPQ2d 1385 (US 2007) at page 1395.
Additionally, Examiner notes StemMACS teaches effective concentrations of LDN193189 for cell culture applications range from 0.01µM to 1µm (p1, 2.1) (i.e., claim 18). In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). MPEP 2144.05
Thus McKeon, in view of StemMACS makes obvious claims 16 and 18 and therefore said claims are properly rejected.
Claim 21 is rejected under 35 U.S.C. 103 as being unpatentable over McKeon in view of Yi (Yi, et al., Nature Scientific Reports (2016) 6:36303; PTO 892).
In regards to claim 21, McKeon does not teach wherein culturing is performed by a subfractionation culturing method (SCM).
Yi teaches the isolation of glandular stem cells (GSCs), i.e., salivary gland epithelial stem cells, from a small biopsy specimen from human parotid glands. Yi teaches single colony-forming unit-derived clonal cells (i.e., monoclonal cells) were isolated through a modified subfractionation culture method (Abstract; p7 last paragraph).
Yi teaches stem/progenitor cells isolated by conventional methods generally produce a mixed and heterogeneous population. The isolated cells may readily undergo cell death or differentiation during ex vivo culture expansion unless they are appropriately cultured. Yi teaches a modified subfractionation culture method for rapid enrichment of single CFU-derived clonal GSCs (i.e., monoclonal cells derived from salivary gland epithelial stem cells). Yi teaches said subfractionation method can be applied to isolation and expansion of highly homogenous human GSCs (i.e., salivary gland epithelial stem cells) (p10, 1st full paragraph).
Thus, it would have been obvious to a POSITA, before the effective filing date of the claimed invention, to combine the teachings of McKeon and Yi. A POSITA would have been so motivated due to McKeon teaching a culture media system that is useful for the isolation and epigenetically stable propagation of stem cells in culture, wherein the stem cells are derived from stratified epithelial tissues and further teaching cloned human epithelial stem cells derived from salivary gland and Yi teaching a modified subfractionation culture method for rapid enrichment of single CFU-derived clonal GSCs (i.e., monoclonal cells derived from salivary gland epithelial stem cells). A POSITA would have been motivated to combine the subfractionation culture method of Yi with the culture media system of McKeon to have the most beneficial culture media and system for producing monoclonal cells derived from salivary gland epithelial stem cells or progenitor cells. A POSITA would have had a reasonable expectation of success in combining said teachings due to all studying culture methods for isolating tissue-specific epithelial stem cells from small amounts of tissue and culturing monoclonal epithelial stem cells.
Thus, the claim is obvious and is properly rejected.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KATHERINE R SMALL whose telephone number is (703)756-4783. The examiner can normally be reached Monday - Friday 8:30am-4pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Chris Babic can be reached on 571-272-8507. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/KATHERINE R SMALL/Examiner, Art Unit 1633
/EVELYN Y PYLA/Primary Examiner, Art Unit 1633
