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 without traverse of Group II (Claims 30-35) in the reply filed on April 27, 2026 is acknowledged. Claims 1,4-10,12-18,21-22,36-39, and 41-42 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected Groups I and III, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on April 27, 2026.
Claim Objections
Claims 30-35 are objected to because of the following informalities: The names of the factors listed in the claims are not clearly written with their abbreviations. For example, “SCF” should be written as –Stem Cell Factor (SCF)--.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 30-35 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of generating bovine primordial germ cell-like cells in vitro comprising administering to bovine embryonic stem cells FGF, activin A, and a GSK3 inhibitor to induce bovine formative cells or administering to bovine embryonic stem cells activin A, a GSK3 inhibitor, and a serum replacement to induce bovine mesoderm-like cells; and administering to the bovine formative cells or the bovine mesoderm-like cells LIF, SCF, EGF, and BMP to induce bovine primordial germ cell-like cells, does not reasonably provide enablement for a method for generating bovine primordial germ cell-like cells in vitro comprising: administering to the bovine embryonic stem cells an inducer of FGF signaling, an inducer of activin A signaling, an inducer of WNT signaling to induce bovine formative cells or administering to bovine embryonic stem cells an inducer of activin A signaling, an inducer of WNT signaling, and a serum replacement to induce bovine mesoderm-like cells; and administering to the bovine formative cells or the bovine mesoderm-like cells an inducer of LIF signaling, an inducer of SCF signaling, an inducer of EGF signaling, and an inducer of BMP signaling to induce bovine primordial germ cell-like cells. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The test of enablement is whether one skilled in the art could make and use the claimed invention from the disclosure in the application coupled with information known in the art without undue experimentation (United States v. Telectronics, Inc. 8 USPQD2d 1217 (Fed. Cir. 1988)). Whether undue experimentation is required is a conclusion reached by weighing several factors. These factors were outlined in Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Inter. 1986) and again in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988) and include the following:
While determining whether a specification is enabling, one considers whether the claimed invention provides sufficient guidance to make and use the claimed invention, if not, whether an artisan would require undue experimentation to make and use the claimed invention and whether working examples have been provided. When determining whether a specification meets the enablement requirements, some of the factors that need to be analyzed are: breadth of the claims, the nature of the invention, the state of the prior art, the level of one of ordinary skill, the level of predictability in the art, the amount of direction provided by the inventor, the existence of working examples, and whether the quantity of any necessary experiment to make and use the invention based on the content of the disclosure is undue.
Nature of the Invention:
The claims recite processes of generating bovine primordial germ cell-like cells. One process recites administering an inducer of activin A signaling, an inducer of WNT signaling, and an inducer of FGF signaling to a population of bovine embryonic stem cells to create bovine formative cells. These bovine formative cells are subsequently exposed to an inducer of LIF signaling, an inducer of SCF signaling, an inducer of EGF signaling, and an inducer of BMP signaling to create bovine primordial germ cell-like cells.
Another process recited in the claims includes administering an inducer of activin A signaling, an inducer of WNT signaling, and a serum replacement to induce a population of bovine embryonic stem cells to create bovine mesoderm-like cells. These bovine mesoderm-like cells are subsequently exposed to an inducer of LIF signaling, an inducer of SCF signaling, an inducer of EGF signaling, and an inducer of BMP signaling to create bovine primordial germ cell-like cells.
Breadth of the Claims:
The claims are so broad that they encompass agents that can induce the following factors: activin A, EGF, FGF, LIF, SCF, etc. An inducer can be any agent/molecule that triggers or activates the factors listed. Claim 32 even states that the factors can be inducers for themselves. For example, activin A can be an inducer of activin A signaling. The claims are so broad that the claims encompass methods in which the inducer of a factor can be present without the actual factor.
For purposes of discussion FGF, activin A, GSK3 inhibitor, BMPs, LIF, SCF, EGF, and a serum replacement are going to be referred to in the discussion as factors since they are the key components that must be present. The other compounds/molecules listed in claims 32 and 34 will be referred to as inducers.
Teachings from the Prior Art:
Saitou (US 20130143321) discloses that bovine embryonic stem cells can be differentiated into bovine formative cells by exposing the embryonic stem cells to a combination of FGF, activin A, CHIR99021 (a GSK3 inhibitor/Wnt agonist). These factors must be present in order to generate the desired bovine formative cells (Paragraph 145 of Saitou). Saitou does not expressly state that inducers of these factors must be present. The bovine formative cells of Saitou are then exposed to LIF, SCF, EGF, a BMP (BMP4 and BMP8b), and KSR—Knockout serum Replacement to induce bovine primordial germ cell-like cells (Paragraph 145 of Saitou). The factors recited in instant claim 30 are required and not their inducers.
Saitou II (US 20180187147) teaches that bovine embryonic stem cells can be differentiated into bovine mesoderm-like cells by exposing the bovine embryonic stem cells to activin A, CHIR99021 (a GSK3 inhibitor/Wnt agonist), and a serum replacement (Paragraphs 93-98 of Saitou II). Saitou II further teaches that these cells can be further differentiated into bovine primordial germ like cells by exposing the bovine mesoderm-like cells to LIF, SCF, EGF, BMP (Paragraphs 32, 112-120). The factors recited in instant claim 30 are required and not their inducers.
Both references acknowledge that the factors recited in claim 30 are required to generate bovine primordial germ like cells.
Claim 32 provides a laundry list of inducers for the factors listed in claim 30. The list of activin A inducers is particularly problematic because not all the activin A inducers listed in claim 32 trigger or activate activin A .
Claim 32 lists examples of inducers of activin A activity that include the following: stauprimide, SB-431542, A01, GDF8, Conophylline. These examples are not true activin A inducers. Stauprimide is not known to be an inducer of activin A signaling. Stauprimide is known to prime/sensitize human and murine embryonal stem cell cultures so that they are able to undergo a more efficient and improved differentiation process (Millipore Sigma/Sigma-Aldrich Fact Sheet—5/26/2026).
SB-431542 is not recognized currently as an inducer of activin A signaling. Instead, SB-431542 is actually an inhibitor of endogenous activin (Abstract of Inman). The abstract is present in Inman’s article, “SB-431542 is a potent and specific inhibitor of transforming growth factor-beta superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7” Mol Pharmacol 62 65-74, 2002.
A01 is not a recognized inducer of activin A. According to the description of the Biotechne/Tocris reference, “A01 is a high affinity Smurf1 E3 ubiquitin ligase inhibitor…Attenuates Smurf1-mediated Smad 1/5 degradation and enhances BMP (bone morphogenic protein) signaling. Potentiates BMP-2-induced osteoblastic activity in C2C12 myoblasts and MC3T3-E1 osteoblast precursor.” It does not appear to have any direct impact on activin A activity.
GDF8 like activin A is a negative regulator of skeletal muscle mass. However, GDF8 does not directly induce activin A as discussed in the entire document of Trotter et al. “GDF8 and activin A are the key negative regulators of muscle mass in postmenopausal females: a randomized phase I trial” Nat Commun. 2025 16:4376.
Conophylline is a differentiation inducer like activin A; however, it does not induce activin A (Abstract of Kojima et al. “Conophylline: A novel differentiation inducer for pancreatic beta cells” The International Journal of Biochemistry and Cell Biology 38 (2006) 923-930.
The prior art requires that specific factors listed in claim 30 be present when generating primordial germ cell-like cells. However, the majority of other inducers listed in claim 32 are not required to be present in order for bovine primordial germ cell-like cells to be generated.
Applicants Specification/Guidance/Working Examples:
Applicants specification states the following on page 33, paragraph 106:
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Paragraph 106 of the specification is stating that factors such as activin A, FGF, GSK3 inhibitor/Wnt agonist, serum free medium are required. Working example 7 of applicants specification also requires the factors recited in claim 30. The other inducers mentioned in claim 32 do not necessarily have to be included. Working example 7 further teaches that the following factors must be present: LIF, SCF, EGF, BMP to generate primordial germ-like cells.
Conclusion: The specific factors recited in claim 30 are the factors required to differentiate the bovine embryonic stem cells into progenitor (intermediate) cells and then into primordial germ cell-like cells. The embryonic stem cells (starting cell population) can be exposed to FGF, activin A, a GSK3 inhibitor to generate bovine formative cells (an intermediate cell population). The embryonic stem cells (starting cell population) can be exposed to activin A, a GSK3 inhibitor, and a serum replacement to induce bovine mesoderm-like cells (another intermediate cell population). These two intermediate cell populations can be exposed to LIF, SCF, EGF, BMP in order to generate the bovine primordial germ cell-like cells. Therefore, claims that require these specific factors are enabled. Additional components such as the inducers recited in claims 32 and claim 34, but not claim 30 do not appear to be required in the prior art or in the specification when generating primordial germ-like cells although they may help with the activation of factors recited in claim 30. There is no teaching in the prior art that the inducers without the main factors can produce the primordial germ cell-like cells. Applicants have not provided working examples that show that the inducers by themselves without the key factors can produce the primordial germ cell-like cells. Furthermore, many of the activin A inducers listed in claim 32 do not appear able to induce activin A activity. The claims need to be amended to require the key factors. For example “inducer of activin A” can be amended to –activin A--.
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.
Claim 35 is 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.
The first portion of claim 35 appears to be referring to the differentiation process where bovine embryonic stem cells are induced to differentiate into bovine formative cells, not bovine mesoderm-like cells since FGF, activin A, and CHIR99021 (a Wnt agonist) are required. In order to differentiate embryonal stem cells into bovine mesoderm-like cells, the following factors are required: activin A, a Wnt agent, and a serum replacement; this is not recited in the limitations where the embryonal stem cells are differentiated into the intermediate cell types. There was a portion that mentioned the bovine mesoderm-like cells; however, that portion has been crossed out in the latest claim amendment.
An additional limitation of claim 35 that discusses differentiating the intermediate cells types into the PGCLCs recites “administering to the bovine formative cells or the bovine mesoderm-like cells further comprising administering a serum replacement to produce bPGCLCs.” This causes indefiniteness because the first part of claim 35 recites factors that produce bovine formative cells as the intermediate cell type not, both bovine formative cells and bovine mesoderm-like cells.
Claim Rejections - 35 USC § 102
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.
Claims 30-32 and 34-35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Saitou (US 20130143321)
Saitou discloses administering to bovine embryonic stem cells (starting cell population) in-vitro: FGF (bFGF), activin A, a Wnt agonist (CHIR99021) to induce bovine formative cells (an intermediate cell population) (Paragraphs 142 and 144 of Saitou). Saitou further teaches administering to the bovine formative cells (intermediate cells): LIF (Invitrogen recombinant LIF), SCF, EGF, BMP (BMP4 and BMP8b), and KSR—KnockOut Serum replacement (serum replacement) to induce bovine primordial germ cell-like cells (PGCLCs) (Paragraph 145 of Saitou) as in instant Claims 30,32,34,35. The Wnt signaling agonist (CHIR99021) inhibits GSK3 (Paragraph 142 of Saitou) as in instant Claim 31.
The reference anticipates the claim limitation.
Claims 30,33-34 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Saitou II (US 20180187147).
Saitou II discloses administering to bovine embryonic stem cells in-vitro activin A (Paragraphs 96-97 of Saitou II), (a GSK-3β inhibitor/CHIR99021/Wnt agonist—Paragraph 98 of Saitou II), and a serum replacement (Paragraph 94 of Saitou II) to induce bovine mesoderm-like cells (Paragraphs 93-98 of Saitou II). Saitou II teaches administering to the bovine mesoderm-like cells (the intermediate cells): LIF (leukemia inhibitory factor), SCF (Stem Cell Factor), an inducer of EGF signaling (EGF/epithelial cell growth factor), and BMP (BMP2, BMP4, BMP7, and BMP8a) to induce bovine primordial germ like cells (PGCLCs) (Paragraphs 32,112-120 of Saitou II) as in instant Claims 30 and 33, 34.
The reference anticipates the claim limitation.
Conclusion
All claims stand rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAUREN K VAN BUREN whose telephone number is (571)270-1025. The examiner can normally be reached M-F:9:30am-5:40pm; 9:00-10:00pm.
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LAUREN K. VAN BUREN
Examiner
Art Unit 1638
/PETER PARAS JR/Supervisory Patent Examiner, Art Unit 1632
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