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
Claims 1 – 9 are pending.
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 1 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.
Regarding claim 1, the phrase “the stromal extracellular matrix-containing gel contains the stromal extracellular matrix- containing gel in an amount of 70 vol% or more” renders the claim indefinite because it is unclear how the ECM-containing gel can contain only 70% of itself.
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.
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.
Claims 1 – 6 are rejected under 35 U.S.C. 103 as being unpatentable over Abbas et al. (Generation of a three-dimensional collagen scaffold-based model of the human endometrium, Interface Focus, Vol. 10, No. 2, 6 April 2020, page 20190079, XP093166192; cited on IDS, hereinafter Abbas), in view of Allbritton (U.S. Patent Application Publication No. 2019/0211296 A1) and Drury et al. (Hydrogels for tissue engineering: scaffold design variables and applications, Biomaterials 24 (2003) 4337 – 4351; hereinafter Drury).
Regarding claims 1 – 6, Abbas teaches the isolation and embedment of stromal cells and endometrium organoid (EO) fragments (p. 3 – 4, Sections 2.3 and 2.4) into Matrigel and further seeded onto scaffolds for co-culture experiments. Abbas further discloses in Figure 1a, a schematic of the human endometrium that shows a continuous luminal and non-luminal structure; and Figure 1b discloses how porous collagen scaffolds are used to develop a model of the endometrium. Furthermore, Abbas teaches the use of type I collagen (p.3, Section 2.1) scaffolds in order to provide structural support for endometrial cells to adhere to (p. 3 – 4, Section 2.4); have a permissive environment that enables cells to grow and produce their own extracellular matrix (ECM); and to study cell migration (p. 2, Second Paragraph). Finally, Abbas teaches that the EO fragments, once seeded, start the formation of luminal-like structures (p. 8, Section 3.3; Figure 4) on the type I collagen scaffold. Abbas teaches that their porous collagen scaffolds are produced by the lyophilization (Fig. 1b) of an aqueous slurry of collagen I.
However, Allbritton discloses methods to generate polymer scaffolds that include collagen hydrogels (para. [0005]) for the improvement of molecular transport in luminal surfaces (para. [0003]; [0112 – 0113]) of spheroidal organoids. Albritton further discloses/provides motivation for fabricating the scaffold (para. [0064], e.g. collagen, gelatin) at different densities is in order to mimic the biophysical microenvironment at about 0 – 49 wt % polymer to about 51 – 100 wt % water (para. [0064]).
Drury discloses, in a review article on hydrogels for tissue engineering, a variety of hydrogels that have a water content of > or = 30% by weight. This suggests that the 70 vol% gels have been in use for tissue fabrication (p. 4338, 1st full paragraph) since 2003.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the lyophilized type I collagen scaffold of Abbas with the hydrogel of Allbritton and Drury in order to better mimic the biophysical microenvironment in terms of luminal surface availability and formation (non-luminal included), permeability, stiffness, and presence of ECM components in the endometrium model of Abbas.
Claims 7 – 8 are rejected under 35 U.S.C. 103 as being unpatentable over Abbas, Allbritton, and Drury as applied to claims 1 – 6 above, and further in view of Buck et al. (Interaction of human trophoblast cells with gland-like endometrial spheroids: a model system for trophoblast invasion, Human Repro, Vol. 0, No. 0 pp. 1 – 11, 2015; cited on IDS, hereinafter Buck).
Regarding claims 7 – 8, Abbas, Allbritton, and Drury teach all of the elements of the current invention as stated above except for an endometrial implantation model. However, Buck discloses an endometrial model system that mimics implantation and invasion events occurring in vivo. The single cell suspensions of endometrial epithelial cells (EEC) are mixed with Matrigel and plated individually into the center of glass chambers to solidify (pp. 2 – 3, Combined culture of EEC spheroids and monolayers; Figure 1a – c). At Day 4 of the combined 2D/3D EEC cultures, trophoblast AC-1M88 (embryonic) cells are added (p. 3, Confrontation of EEC monolayers and spheroids with trophoblast cells; Figure 1d – f). Lumen formation was assessed by staining the tight junction protein ZO-1 (Figures 2; 3c and g). Human trophoblast – endometrial interactions are depicted in Figures 4 – 6.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the endometrial implantation model of Buck and the motivation from the teaching of Abbas, Allbritton, and Drury to use type I collagen-gel scaffolds to provide structural support, facilitate endometrial cell migration, and improve luminal and non-luminal structure formation (Abbas – p. 8, Section 3.3; Figure 4) in the process of generating an adequate three-dimensional implantation model of the endometrium.
Claim 9 is rejected under 35 U.S.C. 103 as being unpatentable over Abbas, Allbritton, Drury, and Buck as applied to claims 7 – 8 above, and further in view of Schmitz et al. (Role for the endometrial epithelial protein MFG-E8 and its receptor integrin αvβ3 in human implantation: results of an in vitro trophoblast attachment study using established human cell lines, Fertility and Sterility, Volume 101, Issue 3, 2014, pp. 874-882; hereinafter Schmitz).
Regarding claim 9, Abbas, Allbritton, Drury, and Buck teach all of the limitations of claim 7 except an endometrial implantation model where the embryonic cells form spheroids or organoids. However, Schmitz discloses a common in vitro model for studying early implantation events (p. 875, last paragraph of Introduction), in which the embryonic cells (Jar cells) form spheroids when cultured under appropriate conditions to mimic early embryogenesis.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the endometrial implantation model of Buck, the type I collagen (gel) scaffolds of Abbas, Allbright, and Drury, with the motivation of Schmitz’s teaching on the use of spheroid-forming embryonic cells to engineer an adequate model for studying early implantation events.
Response to Arguments
Applicant’s arguments, see p. 4 of The Remarks, filed 06/29/2026, with respect to the 102 – Anticipation rejection of claims 1 – 6 under 102 have been fully considered and are persuasive. Therefore, the rejection has been withdrawn. However, upon further consideration, a new ground(s) of rejection is made in view of Abbas, Allbritton, and Drury. Allbritton discloses methods to generate polymer scaffolds that include collagen hydrogels. Drury discloses hydrogels for tissue engineering.
Applicant argues that Abbas fails to teach or suggest each element of the claim, in particular porous collagen scaffolds that are not gel. The rejection has been withdrawn, and a new rejection based on the amended hydrogel composition has been added in view of Abbas, Allbritton, and Drury. Allbritton discloses methods to generate polymer scaffolds that include collagen hydrogels. Drury discloses hydrogels for tissue engineering. The type I collagen of Abbas at the composition (polymer to water) concentrations of Allbritton and Drury would generate the porous collagen gel scaffold that the applicant claims is not in Abbas. Thus, the luminal and non-luminal structure continuously forming are characteristics of the type I collagen gel scaffold generated by combining Abbas, Allbritton, and Drury.
Claims 7 and 8 were rejected under 35 U.S.C. 103 over Abbas in view of Buck. The rejection of each claim has been maintained and modified to include claims 1 – 6 in view of Abbas, Allbritton, and Drury.
Applicant argues that Abbas in view of Buck, alone or in combination, fail to make out a prima facie case of obviousness. Abbas has been modified to include Allbritton and Drury. Applicant argues that Buck uses laminin and Matrigel. However, paragraph [0019] of the instant applications’ specification includes the usage of laminin and Matrigel in stromal extracellular matrix containing gel. Buck
Claim 9 was rejected under 35 U.S.C. 103 over Abbas in view of Schmitz. The rejection of the claim has been maintained and modified to include claims 7 – 8 in view of Abbas, Allbritton, Drury, and Buck.
Applicant argues that Abbas, Buck, and Schmitz, alone or in combination, fail to make out a prima facie case of obviousness. Abbas has been modified to include Albritton and Drury. Buck does disclose an endometrial model system that mimics implantation and invasion using Matrigel. Schmitz’s common in vitro model for studying early implantation events provides the motivation for generating a more accurate spheroid-forming embryonic/implantation model by disclosing that their model mimics early embryogenesis.
Conclusion
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to WALTER JACKSON III whose telephone number is (571)272-0247. The examiner can normally be reached M-F 9:00A - 5:00P.
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/WALTER JACKSON III/ Examiner, Art Unit 1638
/Tracy Vivlemore/ Supervisory Primary Examiner, Art Unit 1638
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