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 .
Claim Status
Amendments to the claims filed 26 Jun 2026 are acknowledged. Claims 9-10, 19, and 21 are presently amended. Claims 15-18 and 20 were previously canceled. Claims 1-14, 19, and 21-24 are pending.
Election/Restriction
Applicant's election with traverse to Group I, drawn to claims 1-8 and 11-13, in the reply filed 26 Jun 2026 is acknowledged.
Applicant traverses on the grounds that the subject matter of all the claims is sufficiently related that a thorough search on any one of the Groups would encompass the other Groups. This is not found persuasive because the inventions are held to be independent and distinct, rationale for which is provided in each requirement for restriction. Consequently, the inventions are classified in different classes and subclasses, and the inventions would require searching of different fields. See MPEP § 808.02. Moreover, a reference that anticipates in the invention of one group may not anticipate, or even make obvious, the invention of the other Groups.
The requirement for restriction of Groups I, II, and III dated 27 Apr 2026 is still deemed proper and is therefore made FINAL.
Claims 9-10, 14, 19, and 21-24 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim.
Claims 1-8 and 11-13 are presented for examination on the merit.
Information Disclosure Statement
The listing of references in the specification 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
Use of the terms KnockOut™ Serum Replacement, Invitrogen®, Gibco®, and GlutaMAX®, which are trade names or marks used in commerce, has been noted in this application. The term should be accompanied by the generic terminology, the term should be capitalized wherever it appears, and, 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) is 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 Objections
Applicant is advised that should claims 1-4 be found allowable, claims 7-8 and 11-12 will be objected to under 37 CFR 1.75 as being substantial duplicates thereof. The following pairs of claims are substantial duplicates of each other: 1 and 7, 2 and 8, 3 and 11, and 4 and 12. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m).
Claims 1-4 recite identical method steps as the corresponding claims 7-8 and 11-12 with the only difference being the intended use of "separating" recited in claims 1-4 or "producing" in claims 7-8 and 11-12. If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention’s limitations, then the preamble is not considered a limitation and is of no significance to claim construction. See MPEP §2111.02. In the present case, a method for separating and a method for producing do not provide manipulative differences such that a different result is obtained. Accordingly, the pairs of claims are not patentably distinct.
Claims 2 and 8 are objected to because of the following informalities:
The first instance of any abbreviation recited in the claims, such as EpCAM, should be accompanied by the full, written out term, then the abbreviation may be used alone thereafter.
Appropriate correction is required.
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 1, 7, and 13 are rejected under 35 U.S.C. § 103 as being unpatentable over Kuchenbauer (F. Kuchenbauer, et al., Mol Cell Endocrinol, 2001) in view of Farnoud (M.R. Farnoud, et al., Int J Cancer, 1996, previously cited in PTO-892 filed 27 Apr 2026) and Chen (J. Chen, et al., Endocrinology, 2005).
Kuchenbauer teaches a method of separating (or producing) pituitary hormone-producing cells from rat brain for culturing in vitro (Abstract). The method comprises 1) isolating pituitary glands from the brains of adult male Sprague-Dawley rats (cell aggregate comprising adenohypophysis and hypothalamic neuroepithelial tissue, claims 1 and 7), 2) dispersing cells by digesting sliced pituitary gland tissue in collagenase and hyaluronidase followed by washing in Dulbecco's Modified Eagle's Medium (DMEM) (separating, claim 1, producing cells, claim 7), and 3) culturing the separated cells (Materials and Methods § 2.2 p. 142). The isolated cells produce adrenocorticotropic hormone (ACTH, claim 13) (Results § 3.1 pp. 143-144).
Kuchenbauer is silent with regard to CD49c as required by claims 1, 7, and 13.
However, Kuchenbauer further teaches that interaction of cells with surrounding extracellular matrix (ECM) proteins is mediated through α and β integrin subunits and that ECM interaction influences hormone production in the pituitary gland (Abstract and Introduction). Kuchenbauer further teaches that their study on the effect of ECM components on pituitary cell hormone production was limited by contaminating fibroblasts that secrete ECM (Methods 2.2 p. 142).
Farnoud teaches that all parenchymal cells in normal human anterior pituitary gland stain strongly for integrin α3 (ITGA3, another term for CD49c), which includes ACTH-producing cells (Results p. 46-47 and Fig. 1). Farnoud further teaches that none of the cells in the connective tissue compartment of the normal anterior pituitary gland express CD49c, which includes fibroblasts (Results p. 47 and Fig. 2).
Chen teaches that fluorescence-activated cell sorting (FACS) can be used to isolate specific pituitary cell populations, which can then reaggregate in culture (Materials and Methods p. 3987 and Results p. 3992). Chen teaches that infusion of the pituitary gland with Hoescht 33342 positively selects for main population cells, which can then be sorted from side population cells, which do not express growth hormone (GH), prolactin (PRL), or luteinizing hormone (LH) (Introduction, Results p. 3990, and Fig. 2C). Therefore, a skilled artisan would recognize that FACS can be used as a tool to enrich hormone-producing cells from the pituitary gland by using a positive selection marker.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the method of separating pituitary hormone-producing cells from hypothalamic neuroepithelial tissue and purification to remove fibroblasts as taught by Kuchenbauer with using CD49c as a marker to distinguish pituitary hormone-producing cells from fibroblasts as taught by Farnoud and FACS to isolate pituitary hormone-producing cell populations as taught by Chen to arrive at the claimed invention. One would be motivated to make such a combination as Kuchenbauer teaches that studying pituitary hormone-producing cells in vitro is limited by fibroblast contamination and that use of a marker for an α integrin, such as CD49c, would enrich hormone-producing cells. One would have a reasonable expectation of success in making the combination as Farnoud teaches that 100% of pituitary hormone-producing cells express CD49c and as 0% of fibroblasts in the pituitary gland express CD49c and as Chen demonstrates that FACS using a positive selection marker can be used to enrich hormone-producing cells from the pituitary gland.
Claims 1-8 and 11-13 are rejected under 35 U.S.C. § 103 as being unpatentable over Kodani (JP 2018011527A, 2018, citations are to translation of the originally filed application provided by the JPO generated 19 Jul 2016) as evidenced by Suga (H. Suga, et al., Nature, 2011) in view of Farnoud (M.R. Farnoud, et al., Int J Cancer, 1996, previously cited in PTO-892 filed 27 Apr 2026) and Zimmer (B. Zimmer, et al., Stem Cell Rep, 2016).
Regarding claims 1-2, 5, and 7-8, Kodani teaches a method of separating cells that express epithelial cell adhesion molecule (EpCAM, claims 2 and 8) by magnetic assisted cell sorting (MACS) from a cell aggregate containing adenohypophysis and hypothalamic neuroepithelial tissue (par. 2 and 8 and Fig. 12, 14, and 16). Kodani teaches that the separation method may be applied to cell aggregates generated using a SFEBq method, which comprises differentiation of embryonic stem cells into a cell aggregate comprising adenohypophysis and hypothalamic neuroectoderm (hypothalamic neuroepithelial tissue, claims 1 and 7, obtain a cell aggregate by inducing differentiation of pluripotent stem cells, claim 5) (Kodani par. 2, 37 and Suga Abstract and p. 1 2nd par.). Kodani teaches using EpCAM as a negative selection marker for separating hypothalamic progenitor cells from EpCAM-positive non-hypothalamic progenitor cells, which would include pituitary hormone-producing cells in the adenohypophysis (par. 8). Although Kodani teaches using EpCAM as a negative selection marker for purifying hypothalamic progenitor cells, a skilled artisan would recognize that EpCAM could, therefore, be used as a positive selection marker in a panel for isolating pituitary hormone-producing cells.
Regarding claim 6, the cell aggregate produced by the SFEBq method taught by Kodani and as evidenced by Suga comprises pituitary placode and Rathke's pouch (Suga Abstract, p. 1, Results .p. 58, and Fig. 2j).
Regarding claim 13, pituitary progenitors in the cell aggregate produced by the SFEBq method taught by Kodani and as evidenced by Suga produce adrenocorticotropic hormone (ACTH), growth hormone (GH), prolactin (PRL), luteinizing hormone (LH), follicle-stimulating hormone (FSH), and thyroid stimulating hormone (TSH) (Results pp. 59-60 and Fig. 3c-3d and 3k-3r).
Kodani does not teach separation of cells expressing CD49c as required by claims 1-8 and 7-13; a method of separating CD49c comprising a culture step as required by claims 3 and 11; use of the negative selection markers CD90, CD29, CD44, CD58, or CD166 to separate cells as required by claims 4 and 12.
However, regarding claims 1-8 and 7-13; Farnoud teaches that all parenchymal cells in normal human anterior pituitary gland (adenohypophysis) stain strongly for integrin α3 (ITGA3, another term for CD49c), which includes endocrine cell types that produce ACTH, GH, PRL, LH, FSH, and TSH (Results pp. 46-47 and Fig. 1).
Furthermore, regarding claims 1-8 and 7-13; Zimmer teaches a similar method to Kodani for generating a cell aggregate comprising adenohypophysis generated from pluripotent stem cells but uses a hypothalamic-conditioned medium rather than direct contact with hypothalamic neuroectoderm cells (Abstract and Results p. 862). Zimmer teaches characterization of pituitary hormone-producing adenohypophyseal cells in the cell aggregate by dispersal of the cells from the aggregate and measuring the percent of cells positive for cell surface markers and found that 100% of the cells express CD326 (another term for EpCAM) and about 50% of cells express CD49c (Results pp. 864-865, Supp Experimental Procedures 7th section, and Supp Fig. 6b). Zimmer further teaches that the "cell-surface epitope screen presents candidate markers that may be suitable for isolating specific hormone lineages" (Discussion p. 869). Therefore, taken with the teachings of Farnoud, a skilled artisan would recognize that EpCAM and CD49c would act as a positive selection markers for pituitary hormone-producing cells and EpCAM would act as a negative selection marker for hypothalamic cells for separating cells in a cell aggregate comprising adenohypophysis and hypothalamic neuroepithelial tissue.
Regarding claims 3 and 11, Zimmer further teaches generation of cell aggregate from pluripotent stem cells induced to differentiate to a pituitary placode state followed by flow cytometry-assisted cell sorting (FACS) (a first step of dispersing the cell aggregate into a cell population), then culturing the dispersed cells on a plates coated with laminin (a second step of culturing the cell population on a culture vessel coated with laminin), and in some embodiments, the dispersed pituitary cells are grown in co-culture with hypothalamic neuroectodermal cells (Supp Experimental Procedures, 2nd section). Zimmer further teaches that delivery of a highly-defined cell population is desired for orthotopic transplant into the pituitary gland or hypothalamic region for the treatment of pituitary disorders (Discussion p. 869).
Regarding claims 4 and 12, Zimmer further teaches that 0% pituitary hormone-producing adenohypophyseal cells in the cell aggregate express CD166 and less than 20% of cells express CD29, CD44, or CD58 (Supp Fig. 6b). Therefore, a skilled artisan would recognize that using EpCAM as a positive selection marker would yield cells negative for at least one of CD29, CD44, CD58, and CD166.
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the method of separating pituitary hormone-producing cells and hypothalamic cells in a cell aggregate comprising adenohypophysis and hypothalamic neuroepithelial tissue using EpCAM as a negative selection marker taught by Kodani and evidenced by Suga with the method of using EpCAM as a positive selection marker for pituitary hormone-producing cells as taught by Zimmer and CD49c as a positive selection marker as taught by Farnoud and Zimmer to arrive at the claimed invention. One would be motivated to make such a combination as Zimmer teaches that highly defined and purified cells are desired for therapeutic application and that cell surface markers including EpCAM can be used for positive selection of specific hormone-producing populations from a cell aggregate comprising multiple pituitary hormone-producing lineages. One would have a reasonable expectation of success in making the combination as Zimmer teaches that pituitary hormone-producing cells in a cell aggregate produced by a similar method as taught by Kodani and Suga express EpCAM that EpCAM-positive cells comprise CD49c-positive cells and as Farnoud teaches that pituitary hormone-producing cells in situ express CD49c.
Double Patenting
Claims 1-2, 5-8, and 13 of this application is patentably indistinct from claims 1, 7, and 12 of Application No. 17/995,043. Pursuant to 37 CFR 1.78(f), when two or more applications filed by the same applicant or assignee contain patentably indistinct claims, elimination of such claims from all but one application may be required in the absence of good and sufficient reason for their retention during pendency in more than one application. Applicant is required to either cancel the patentably indistinct claims from all but one application or maintain a clear line of demarcation between the applications. See MPEP § 822.
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 § 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 1-2, 5-8, and 13 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 7, and 12 of copending Application No. 17/995,043 (reference application, '043 hereafter) in view of Farnoud (M.R. Farnoud, et al., Int J Cancer, 1996, previously cited in PTO-892 filed 27 Apr 2026) and Zimmer (B. Zimmer, et al., Stem Cell Rep, 2016). This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claim 1 '043 recites a method for separating pituitary hormone-producing cells and/or progenitor cells thereof comprising a step of separating cells that express EpCAM from a cell aggregate containing adenohypophysis and/or a precursor tissue thereof derived from pluripotent stem cells. Claim 1 of '043 recites each of the elements of claims 1-2, 5, and 7-8 of the immediate application except that the present claims require separation of cells that express CD49c.
Claim 7 of '043 further recites that the precursor tissue is a pituitary placode and/or Rathke's pouch. Claim 7 of '043 recites each of the elements of claim 6 of the immediate application except that the present claim requires separation of cells that express CD49c.
Claim 12 of '043 further recites that the pituitary hormone-producing cells is selected from a cell that produces at least one of growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), follicle-stimulating hormone (FSH), and luteinizing hormone (LH). Claim 12 of '043 recites each of the elements of claim 13 of the immediate application except that the present claim requires separation of cells that express CD49c.
However, Farnoud teaches that all parenchymal cells in normal human anterior pituitary gland (adenohypophysis) stain strongly for integrin α3 (ITGA3, another term for CD49c), which includes endocrine cell types that produce ACTH, GH, PRL, LH, FSH, and TSH (Results pp. 46-47 and Fig. 1).
Furthermore, Zimmer teaches characterization of pituitary hormone-producing adenohypophyseal cells in the cell aggregate by dispersal of the cells from the aggregate and measuring the percent of cells positive for cell surface markers and found that 100% of the cells express CD326 (another term for EpCAM) and about 50% of cells express CD49c (Results pp. 864-865, Supp Experimental Procedures 7th section, and Supp Fig. 6b). Therefore, taken with the teachings of Farnoud, a skilled artisan would recognize that using EpCAM as a positive selection marker for separating cells in a cell aggregate comprising adenohypophysis and hypothalamic neuroepithelial tissue would yield pituitary hormone-producing cells that express both EpCAM and CD49c. Zimmer further teaches that delivery of a highly-defined cell population is desired for orthotopic transplant into the pituitary gland or hypothalamic region for the treatment of pituitary disorders (Discussion p. 869).
Therefore, it would have been obvious to one of ordinary skill in the art, before the effective filing date of the claimed invention, to combine the method of separating pituitary hormone-producing cells and hypothalamic cells in a cell aggregate comprising adenohypophysis and hypothalamic neuroepithelial tissue as presented in claims 1, 7, and 12 of Application No. 17/955,043 with the method of using EpCAM as a positive selection marker for pituitary hormone-producing cells as taught by Zimmer and CD49c as a positive selection marker as taught by Farnoud and Zimmer to arrive at the claimed invention. One would be motivated to make such a combination as Zimmer teaches that highly defined and purified cells are desired for therapeutic application. One would have a reasonable expectation of success in making the combination as Zimmer teaches that pituitary hormone-producing cells in a cell aggregate express EpCAM that EpCAM-positive cells comprise CD49c-positive cells, and as Farnoud teaches that pituitary hormone-producing cells in situ express CD49c.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Eric B Wright whose telephone number is (571) 272-2607. The examiner can normally be reached Mo - Fr, 09:00 a.m. - 05:00 p.m. Eastern. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571) 272-4517.
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Eric B Wright, PhD
Examiner
Art Unit 1632
/Eric B Wright/Examiner, Art Unit 1632
/VALARIE E BERTOGLIO/Primary Examiner, Art Unit 1632
Prosecution Insights