DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Response to Amendments
Applicant's amendments filed 6/01/2026 to claim 1 have been entered. Claims 3-7, 10, 12, 13, 19, 24, 27-29, 31-37, 39, 42-54 are canceled. Claims 1, 2, 8, 9, 11, 14-18, 20-23, 25, 26, 30, 38, 40, and 41 remain pending, and are subject to the election requirement dated 4/02/2026.
Election/Restrictions
Applicant's election with traverse of Group I, presently claims 1, 2, 8, 9, and 11 in the reply filed on 6/01/2026 is acknowledged. The traversal is on the ground(s) that the instant amendments to claim 1 obviate the restriction requirement. This is not found persuasive because the groups of inventions listed above do not relate to a single general inventive concept under PCT Rule 13.1 because, under PCT Rule 13.2, they lack the same or corresponding special technical features for the following reasons: Groups I-IX lack unity of invention because even though the inventions of these groups require the technical feature of the amended organoid composition of claim 1, this technical feature is not a special technical feature as it does not make a contribution over the prior art in view of Quadrato et al. (WO 2017/117547; provided in the IDS dated 2/28/2024) in view of Bruder et al. (WO 2020/053257; provided in the IDS dated 2/28/2024) and Zhu al. (PLoS One (2013), 8(1), e54552, 13 pages; Reference U). Quadrato teaches brain organoids obtained from human pluripotent stem cells (Abstract), comprising cerebral tissue expressing FOXG1 and PAX6 and comprising retinal cells such as retinal ganglion cells and known retinal cell types (page 38, lines 7-19; the paragraph spanning pages 40-41; page 47, lines 14-21), reading in-part on claim 1. While Quadrato does not teach any concentric ring arrangement, Bruder teaches neural organoids exhibiting a plurality of concentric zones exhibiting tissue-specific activity (page 9, lines 19-31). As such, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further formulate the brain organoids of Quadrato into concentric zones according Bruder to predictably subdivide the brain organoids of Quadrato into concentric zones having tissue-specific activity and being more representative of in vivo brain structure. While Quadrato does not teach any PAX2+ cells, Zhu teaches methods of differentiated human pluripotent stem cells into a retinal cyst in vitro, wherein said cyst is PAX2+ and wherein PAX2+ is indicative retinal identify (page 2, paragraph starting “We next identified…” and Fig. 2A). As such, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further differentiate Quadrato’s human pluripotent stem cells in to PAX2+ retinal cells in view of Zhu in view of Zhu to general retinal organoids as Quadrato expressly contemplates retinal organoids as set forth above.
The requirement is still deemed proper and is therefore made FINAL.
Claims 14-18, 20-23, 25, 26, 30, 38, 40, and 41 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 6/01/2026.
Claims 1, 2, 8, 9, and 11 are under consideration on the merits.
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.
Claims 1, 2, 8, 9, and 11 are 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 1 was amended to now recite “PAX2+ optic disc and optic stalk cells”, which blurs the metes and bounds of the claim. “Optic disc” and “optic stalk” are plainly understood as anatomical structures in the developing or mature retina and not cells, so it is unclear if these anatomical structures are or are not required by the claim and what PAX2+ cells are and are not permitted within the scope the claim. Correction is required.
In so much that claims 2, 8, 9, and 11 depend from claim 1 and do not resolve the point of confusion, these claims must be rejected with claim 1 as indefinite.
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 and 2 are rejected under 35 U.S.C. 103 as being unpatentable over Quadrato et al. (WO 2017/117547; provided in the IDS dated 2/28/2024) in view of Bruder et al. (WO 2020/053257; provided in the IDS dated 2/28/2024) and Zhu al. (PLoS One (2013), 8(1), e54552, 13 pages; Reference U).
Quadrato teaches brain organoids obtained from human pluripotent stem cells (Abstract), comprising cerebral tissue expressing FOXG1 and PAX6 and comprising retinal cells such as retinal ganglion cells and known retinal cell types (page 38, lines 7-19; the paragraph spanning pages 40-41; page 47, lines 14-21) as well as contemplating midbrain organoids (page 38, lines 7-19), reading in-part on claim 1. Quadrato teaches FOXG1+ and PAX6+ cells (the paragraph spanning pages 40-41), reading on the telencephalic and ocular progenitors of claims 1 and 2.
Regarding claim 1, Quadrato does not teach any concentric zone arrangement. Regarding claim 1, in view of the indefiniteness rejection above and in the interest of compact prosecution, Quadrato does not teach PAX2+ retinal cells.
Bruder teaches neural organoids exhibiting a plurality of concentric zones exhibiting tissue-specific activity (page 9, lines 19-31), reading on claim 1. Bruder teaches whole-brain organoids comprising retinal cells (Fig. 11a), reading on claim 1. Bruder teaches generating the organoids from induced pluripotent stem cells (the paragraph spanning pages 25-26), reading on claim 1.
Zhu teaches methods of differentiated human pluripotent stem cells into a retinal cyst in vitro, wherein said cyst is PAX2+ and wherein PAX2+ is indicative retinal identify (page 2, paragraph starting “We next identified…” and Fig. 2A), reading on claim 1.
Regarding the concentric zones of claim 1, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further formulate the brain organoids of Quadrato into concentric zones according Bruder. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Bruder and Quadrato are directed towards brain or retinal organoids derived from induced pluripotent stem cells. The skilled artisan would have been motivated to do so because it would be predictably advantageous according to Bruder to further subdivide the brain or retinal organoids of Quadrato into concentric zones having tissue-specific activity and being more representative of in vivo brain structure.
Regarding the PAX2+ retinal cells of claim 1, it would have been obvious to a person of ordinary skill in the art before the invention was filed to further differentiate Quadrato’s human pluripotent stem cells in to PAX2+ retinal cells in view of Zhu to general retinal organoids. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because Quadrato expressly contemplates retinal organoids. The skilled artisan would have been motivated to do so because Zhu teaches that PAX2+ is indicative of retinal cell fate, and so further differentiating Quadrato’s human pluripotent stem cells in to PAX2+ retinal cells would be predictably advantageous to generate the retinal organoids taught by Quadrato.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill before the invention was filed.
Claims 8 and 9 rejected under 35 U.S.C. 103 as being unpatentable over Quadrato, Bruder, and Zhu as applied to claims 1 and 2 above, and further in view of Tanaka et al. (Scientific Reports (2015), 5(8344), 11 pages; Reference V).
The teachings of Quadrato, Bruder, and Zhu are relied upon as set forth above.
Regarding claim 8 and 9, Quadrato, Bruder, and Zhu do not teach retinal ganglion cells expressing the embodiments of POU4F2 (i.e. Brn3b), and/or TUBB3 (i.e. β-III tubulin or Tuj1). Regarding claim 9, Quadrato, Bruder, and Zhu do not teach do not teach retinal ganglion cells expressing TUBB3 (i.e. βIII tubulin).
Tanaka teaches retinal ganglion cells derived from human induced pluripotent cells (Abstract). Tanaka teaches that retinal ganglion cells are Brn3b+ (i.e. POU4F2+) (Figure 2) and axonal β-III tubulin+ (i.e. Tuj1+ or TUBB3+) (Figure 4), reading on claims 8 and 9.
It would have been obvious to a person of ordinary skill in the art before the invention to generate POU4F2+ and TUBB3+ retinal ganglion cells in the retinal organoid composition of Quadrato in view of Tanaka. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Quadrato and Tanaka are both directed towards retinal cell and retinal ganglion cells derived from induced pluripotent stem cells. The skilled artisan would have been motivated to do so because Tanaka teaches that POU4F2 and TUBB3 are known markers for retinal ganglion cells, and so selecting for POU4F2+ and TUBB3+ cells in Quadrato’s methods would predictably yield the retinal ganglion cells taught by Quadrato.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill at the time the invention was made.
Claim 11 is rejected under 35 U.S.C. 103 as being unpatentable over Quadrato, Bruder, and Zhu as applied to claims 1 and 2 above, and further in view of Chatzopoulou et al. (The Journal of Neuroscience (2008), 28(30), 7624-7636; Reference W) and as evidenced by Masuda (Cell Adh Migr (2017), 11(5-6), 524-531; Reference X).
The teachings of Quadrato, Bruder, and Zhu are relied upon as set forth above.
Regarding claim 11, Quadrato, Bruder, and Zhu do not teach retinal ganglion cells expressing CNTN2 (i.e. contactin 2, TAG-1, axonin-1) on the cell surface.
Chatzopoulou teaches that TAG-1 is almost exclusively detected on the surface of neurites of Brn3a+ retinal ganglion cells and the surface of optic tract fibers in mouse embryonic retina (Fig. 2, and page 7626, right column, paragraph starting “To determine where TAG-1 protein…”) as evidenced by Masuda as Matsuda teaches that contactin 2/TAG-1 is a cell-surface molecule belonging to the immunoglobulin superfamily (1st paragraph under the Introduction on page 524), reading on claim 11
It would have been obvious to a person of ordinary skill in the art before the invention to generate CNTN2/TAG-1+ retinal ganglion cells in the retinal organoid composition of Quadrato in view of Chatzopoulou as evidenced by Matsuda. A person of ordinary skill in the art would have had a reasonable expectation of success to do so because both Quadrato and Chatzopoulou are both in-part directed towards mammalian retinal ganglion cells. The skilled artisan would have been motivated to do so because Chatzopoulou teaches that CNTN2/TAG-1+ is a known marker for retinal ganglion cells, and so selecting for POU4F2+ and TUBB3+ cells in Quadrato’s methods would predictably yield the retinal ganglion cells taught by Quadrato.
Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill at the time the invention was made.
Conclusion
No claims are allowed. No claims are free of the art.
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/Sean C. Barron/Primary Examiner, Art Unit 1653
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