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 .
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Election/Restrictions
Applicant's election with traverse of group I, claims 203-215 in the reply filed on 3/31/26 is acknowledged. The traversal is on the ground(s) that the examiner has not provided sufficient to demonstrate burden. This is not found persuasive because the requirement for restriction was made under the requirements for lack of unity, not independent and distinctness.. The requirement for unity of invention is only fulfilled when there is a special technical feature present. See PCT Rules 13.1 and 13.2. A finding of lack of unity among the claims is all that is necessary to establish the appropriateness of a restriction requirement.
The requirement is still deemed proper and is therefore made FINAL.
Claims 203-222 are currently pending
Claims 216-222 are withdrawn as directed to non-elected inventions.
Claims 203-215 are elected and examined on the merits.
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.
Claim(s) 203-204 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Pasca et al., US Publication No. 2022/0364053 (hereinafter Pasca).
Regarding claim 203, Pasca discloses methods of making human striatal and midbrain spheroids (Abstract). Pasca explains that human striatal spheroids produced according to the disclosed methods comprise functional GABAergic medium spine neurons ([0063]). Human cortical spheroids produced according to the disclosed methods comprise glutamatergic neurons ([0064]-[0066]). Midbrain spheroids produced according to the disclosed methods comprise dopaminergic neurons ([0074). Pasca further discloses co-culturing the striatal and cortical spheroids to form cortico-striatal assembloids ([0075]-[0077]). Similarly, midbrain spheroids may be co-cultured with striatal spheroids to produce midbrain-striatal assembloids ([0078]-[0080]). In some embodiments, striatal, cortical, and midbrain spheroids may be co-cultures to produce three-part assembloids ([0081]).
Regarding claim 204, Pasca does not explicitly disclose that the spheroid exhibits one or more properties from the ventral tegmental area, prefrontal cortex, nucleus accumbens, amygdala, hippocampus, somatomotor cortex, somatosensory cortex, parietal lobe, occipital lobe, cerebellum, or temporal lobe. However, this limitation recites the intended result of the method rather than requiring an additional, active method step be performed. MPEP § 2111.04 states “[c]laim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore, since this claim only recites the results of the actively recited method steps (e.g., admixing differentiated neurons and culturing), art reading on the method of claim 203, necessarily results in the same characteristics in the absence of evidence to the contrary.
Therefore, every limitation of claims 203-204 is present in Pasca, and the subject matter is anticipated.
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 205-208, 211, 215 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pasca as applied to claims 203-204 above, and further in view of Pasca et al., (2015) Functional cortical neurons and astrocytes from human pluripotent stem cells in 3D culture. Nature Methods, 12(7): 671-678 (hereinafter Pasca 2015).
Regarding claims 205, Pasca does not explicitly disclose that glial cells, such as astrocytes are admixed with the differentiated neurons. However, Pasca explicitly cites to (and purports to incorporate by reference) Pasca 2015 for methods of producing cortical spheroids ([0064]).
Pasca 2015 explains that the disclosed methods produce cortical spheroids comprising both cortical neurons and astrocytes (Introduction, Identification and verification of astrogenesis in hCSs, Discussion). Therefore, it is implicit that the cortical spheroids of Pasca, which utilizes the same methodology of Pasca 2015, would likewise comprise astrocytes.
Regarding claim 206, Pasca discloses that the spheroids are composed of human cells ([0053]).
Regarding claim 207, Pasca discloses that the cells comprising the spheroids may be derived from human pluripotent stem cells ([0053]-[0054]).
Regarding claim 215, Pasca discloses that one or more of the cells may be genetically modified using known methods in the art, including transfection via viral vector ([0009], [0027], [0049], [0097]).
Regarding claim 208, the combination does not explicitly disclose that the spheroid exhibits one or more properties of cells from the prefrontal cortex. However, this limitation clause recites the intended result of the method rather than requiring an additional, active method step be performed. MPEP § 2111.04 states “[c]laim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore, since this claim only recites the results of the actively recited method steps (e.g., admixing differentiated neurons and culturing), art reading on the method of claim 205, necessarily results in the same characteristics in the absence of evidence to the contrary.
Regarding claim 211, the combination does not explicitly disclose that the spheroid exhibits one or more properties of cells from the ventral tegmental area. However, this limitation clause recites the intended result of the method rather than requiring an additional, active method step be performed. MPEP § 2111.04 states “[c]laim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed” and that such a clause ‘"in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.” Therefore, since this claim only recites the results of the actively recited method steps (e.g., admixing differentiated neurons and culturing), art reading on the method of claim 205, necessarily results in the same characteristics in the absence of evidence to the contrary.
Claim(s) 214 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pasca and Pasca 2015 as applied to claims 205-208, 211, 215 above, and further in view of Song et al., (2019) Assembly of human stem cell-derived cortical spheroids and vascular spheroids to model 3-D brain-like tissues. Scientific Reports, 9: 5977 (cited on IDS dated 8/18/23, hereinafter Song).
Regarding claim 214, the combination does not disclose that the admixing further comprises including endothelial cells, pericytes, or both.
Song discloses methods of forming cortical spheroids comprising vasculature (Abstract, Introduction, Discussion). Song explains that neural-vascular interactions play an important role in brain structure and function such that inclusion of neural-vascular in organoids is critical in developing functional brain organoids (Introduction, Discussion). Song discloses co-culturing neural progenitor spheroids, mesenchymal stem cell spheroids, and endothelial cell spheroids such that they fuse into a hybrid spheroid (Aggregate fusion and cell localization of tri-cultured hybrid spheroids). The hybrid spheroids demonstrate cortical neural differentiation, vascular markers, and markers for astrocytes (Cortical neural differentiation of tri-cultured hybrid spheroids). Song explains that the disclosed methods result in spheroids which demonstrate anatomical features of the blood-brain barrier and accelerates development of 3D cortical tissue (Discussion). Song concludes that the hybrid spheroids allows for formation of spheroids with angiogenic potential, neo-brain patterning, and neural maturation (Introduction, Discussion).
As each of the references are directed to methods of forming neural cortical spheroids, it would be obvious to one of ordinary skill in the art that the references could be combined. A skilled artisan would be motivated to incorporate the endothelial and mesenchymal stem cells of Song into the methods of the combination for more the formation of more functional brain organoids which replicate the blood-brain barrier.
Allowable Subject Matter
Claims 209-210, 212-213 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARA D JOHNSON whose telephone number is (571)270-1414. The examiner can normally be reached Monday-Friday 8:00-4:00 CT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Peter Paras can be reached at (571) 272-4517. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARA D JOHNSON/Primary Examiner, Art Unit 1632
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