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 .
Claims 1-17 are pending in this application.
Election/Restrictions
Applicant's election with traverse of Group I (Claims 1-9) in the reply filed on 01/20/2026 is acknowledged. The traversal is on the ground(s) that Group III includes all of the technical features of Group I and Group VI recites a step of treating with a HIPPO pathway inhibitor. This is not found persuasive because Group III is a product-by-process claim which does not necessarily require that the blastoid be “obtained by” the method of Group I and Group IV requires treating an already formed embryo or immature blastocyst with a HIPPO pathway inhibitor, a feature not found in Group I which is drawn to treating an aggregate of human pluripotent stem cells or trophoblast cells with a HIPPO inhibitor in 3D culture. Claims 10-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 01/20/2026.
The requirement is still deemed proper and is therefore made FINAL.
Claims 1-9 were examined on their merits.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2). Alternatively, Applicant may delete references to color in the description of Fig. 21.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at Pgs. 38, 41 and 57. Applicant is required to delete the embedded hyperlinks and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the terms MATRIGEL™, CELLVIS™ and GELTREX™, which are trade names or marks used in commerce, has been noted in this application. The terms should be accompanied by the generic terminology; furthermore the terms should be capitalized wherever they appear 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 Objections
Claim 8 is objected to because of the following informalities: The claim recites “the seeding of the seeding”. Appropriate correction is required.
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.
Claim 8 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. Claim 8 recites the limitations "endometrial cells", “the blastoid” and ”the layer of endometrial cells”.
There is insufficient antecedent basis for this limitation in the claim as Claim 1 contains no reference to endometrial cells.
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 2 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 2 recites, “wherein the aggregate of hPSCs
and trophoblasts is generated by culturing aggregated hPSCs in a medium further
comprising a HIPPO pathway inhibitor”, however the Claim depends from Claim 1 which already requires culturing aggregated hPSCs and trophoblast cells in a medium comprising a HIPPO pathway inhibitor. 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 § 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 9 are rejected under 35 U.S.C. § 103 as being unpatentable over Rivron et al. (US 9,822,336 B2).
Rivron et al. teaches a method comprising 3D culturing (in a non-adherent surface microwell) an aggregate of mouse embryonic stem (pluripotent) cells and trophoblast cells in a medium comprising one or more of: a Rho/ROCK inhibitor, a modulator of the Tgf pathway, a modulator of the PKC pathway, a modulator of the Wnt pathway, a modulator of the STAT pathway and modulator of the HIPPO pathway (Column 23, Lines 22-30 and Column 38, Claims 1, 4 and 5);
wherein the modulator of the HIPPO pathway may be an inhibitor, such as GPCR ligands (lysophosphatidic acid receptor is a GPCR), such as GPR30 ligands, such as estradiol and tamoxifen (Column 22, Lines 66-67 and Column 23, Lines 1-8);
wherein the cell types for use in the present invention, such as trophoblast cells, pluripotent or totipotent cells, can be isolated from natural embryonic structures of any mammalian animal, in particular a mouse or a rat, and further a horse, cow, pig, sheep, goat, dog, cat, monkey or human (Column 9, Lines 1-5 and 12-15);
wherein the cell aggregate forms an inner cell mass-like tissue, as well as a blastocoel, together surrounded by a trophectoderm-like tissue and the double layered cell aggregate has a diameter of about 10 µm to 200 µm (Column 15, Lines 8-14);
and wherein the present method for obtaining a blastoid bears high promise for identifying novel drug targets and enhances the probability of clinical success of new drugs (Column 33, Lines 47-50), and reading on Claims 1-7.
Regarding the “wherein” clause of Claim 1 and the limitations of Claims 2-6 further limiting that wherein clause, regardless of the inhibitor(s) used in the medium to make the aggregated hPSCs/trophoblasts, it appears the same aggregated hPSCs/trophoblast aggregate would be made by the prior art.
The teachings of Rivron et al. were discussed above.
The reference did not teach a method comprising human pluripotent stem cells (hPSC) and trophoblast cells, as required by Claim 1;
or treating the aggregate with at least one candidate compound, as required by Claim 9.
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Rivron et al. of producing a mouse artificial blastoid/blastocyst (e.g. aggregate) comprising mouse embryonic stem (pluripotent) cells and trophoblast cells to use human embryonic (pluripotent) stem cells because the reference teaches that either source of cells may be used in the process. See the MPEP at 2144.06, II. Those of ordinary skill in the art would have been motivated to make this modification in order to assess the effect of candidate drugs on the artificial blastoid/blastocyst model. There would have been a reasonable expectation of success in making this modification because the reference teaches that the pluripotent stem cells and trophoblasts may be obtained from mice or humans.
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Rivron et al. of producing an artificial blastoid/blastocyst (aggregate) to treat the blastoid/blastocyst with at least one candidate compound because the reference teaches the obtained blastoid bears high promise for identifying novel drug targets and enhances the probability of clinical success of new drugs. Those of ordinary skill in the art would have been motivated to make this modification in order to assess the effect of candidate drugs on the artificial blastoid/blastocyst model. There would have been a reasonable expectation of success in making this modification because the reference suggests the use of the artificial blastoid/blastocyst model in drug testing.
With regard to the limitation of Claim 9, “for testing or screening a candidate compound and/or candidate genetic alteration on having an effect at blastoid formation and/or implantation of a blastoid into a layer of endometrial cell”, this amounts to a recitation of an intended use which does not result in a structural/manipulative difference which patentably distinguishes between the claimed invention and the prior art.
The Examiner notes that while the reference does not provide a single anticipating embodiment of the claimed invention it does separately provide each claimed element, the only difference being combination of all the elements into a single process. See the MPEP at 2143, I., A., referencing KSR. It would have been obvious to those of ordinary skill in the art to have combined those separately taught elements into a single process in order to produce an artificial blastoid/blastocyst. Those of ordinary skill in the art would have been motivated to make this modification in order to obtain the desired artificial blastoid/blastocyst. There would have been a reasonable expectation of success in making this modification because all the elements are separately taught in the Rivron et al. reference.
With regard to Claim 7, Rivron et al. teaches the cell aggregate forms an inner cell mass-like tissue, as well as a blastocoel, together surrounded by a trophectoderm-like tissue and the double layered cell aggregate has a diameter of about 10 µm to 200 µm (Column 15, Lines 8-14).
Claims 1-7, 8 and 9 are rejected under 35 U.S.C. § 103 as being unpatentable over Rivron et al. (US 9,822,336 B2) as applied to Claims 1-7 and 9 above, in view of Evans et al. (2019).
The teachings of Rivron et al. were discussed above.
Rivron et al. did not teach a method further comprising the stimulation of endometrial cells with a compound selected from estrogen, estrone, estriol, ethinyl estradiol, 17α-ethylnylestradiol, mestranol, progesterone, a progestin, cAMP, and a Wnt-inhibitor, and the seeding of the seeding of the blastoid onto the layer of stimulated endometrial cells that allows the blastoid to attach and invade the layer of endometrial cells, as required by Claim 8.
Evans et al. teaches stimulation of a monolayer of endometrial cells with either estrogen or progestin before seeding with a Trophectoderm spheroid onto the monolayer allowing attachment and invasion of the monolayer (Pg. 8, Fig. 1e, f and Pg. 9, Column 2, Lines 6-23), wherein the model can be used to discriminate between endometrial epithelial cells obtained from “fertile” vs. “infertile” women and is a potential “diagnostic” tool of endometrial infertility (Pg. 5, Abstract).
It would have been obvious to those of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Rivron et al. of producing an artificial blastoid/blastocyst (aggregate) to combine the method with the method of Evans et al. of applying a trophectoderm spheroid to endometrial cells and assessing attachment and invasion of the monolayer because Rivron et al. provides a blastoid/blastocyst model and Evans et al. provides an embryo/endometrial adhesion model which requires a blastoid/blastocyst/trophectoderm spheroid. Those of ordinary skill in the art would have been motivated to make this modification in order to provide a diagnostic for endometrial infertility in a subject. There would have been a reasonable expectation of success in making this modification because the Rivron reference provides an artificial embryo and Evan teaches a diagnostic method which requires an embryo.
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the Examiner should be directed to PAUL C MARTIN whose telephone number is (571)272-3348. The Examiner can normally be reached Monday-Friday 12pm-8pm EST.
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If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Sharmila G Landau can be reached at (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/PAUL C MARTIN/Examiner, Art Unit 1653 02/12/2026