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 Status
Claims 1-15 and 19-21 are pending.
Claims 1-15 have been previously examined.
Claims 19-21 have been examined on the merits.
Response to Arguments / Status of Rejections
RE: Rejection of claims 1-15 over Kuwahara et al (US2017/0313981 A1) in view of Feng et al (Cell Reports, 2016) and evidenced by Rowan et al (Development, 2004):
Applicants traverse the rejection on the grounds that:
One ordinary skill in the art would have no reason to modify the method taught by Kuwahara et al to incorporate the CHK1 inhibitor taught by Feng et al to produce retinal cell or retinal tissue because the experimental disclosure of Feng et al is not directed to retinal cell or tissue differentiation. Stem cell differentiation is context dependent and the teachings for Feng et al does not create any reasonable expectation that a CHK1 inhibitor would have similar effect in the context of retinal differentiation (ectodermal neural lineage).
This argument is not found to be persuasive.
Feng et al does provides motivation for the incorporation of CHK1 inhibitor PD407824 into cell differentiation methods that use BMP signaling activators (See, p4 previous Office Action). The method of Kuwahara et al teaches the use of BMP for retinal cell or retinal tissue differentiation. Feng et al teaches CHK1 inhibitor PD407824 to be useful for stem cell or progenitor fate in differentiation protocols that use BMP signaling activators (See, p2073 col 1 paragraph 1); or in this case, the method of Kuwahara et al for retinal cell or retinal tissue differentiation with BMP activator.
While the teachings of Feng et al, are not directed towards retinal cell or tissue differentiation, it was not used as reference or source for the method of retinal cell or tissue differentiation; Kuwahara et al provided the active steps of the method for retinal cell or tissue differentiation that include the use of BMP activator, which reads on the steps of the claimed method. As previously stated, Feng et al teaches that CHK1 inhibitor PD407824 is useful for stem cell or progenitor fate in differentiation, specifically in methods with a BMP activator, as CHK1 inhibitor enhances sensitivity to BMP (See, p2073 col 1 paragraph 1). Feng et al also details that the concentration of the inhibitor is dependent on that particular differentiation protocol and medium used (See, p2073 col1 paragraph 1). Therefore, Feng et al teaches that the use of PD407824 is not limited to the differentiations that were highlighted in the article.
Example 2 of the instant application demonstrates unexpected superior results in producing a retinal cell or retinal tissue. Applicants state that the inclusion of the PD407824 to BMP leads the aggregated masses to be more spherical than without the inhibitor. Also, Example 3 shows the aggregates have multilayer structure comprising a layer of retinal pigment epithelial (RPE) cells localized on the outside and a layer of neural retinal tissue (NR) localized on the inside. Applicants state that the results in the examples and figures 4 and 5 in remarks (dated 08/07/2026) show that the inclusion of PD407824 produces unexpected results in suppressing differentiation into non-target cells, significantly improving the induction efficiency of the neural retina, and enabling the formation of spherical cell aggregates, set forth in the claims.
This argument is not found to be persuasive.
Feng et al teaches the CHK1 inhibitor, PD407824 would increase the potential of the BMP activator used in a method. Thus, one would have expected the inclusion of CHK1 inhibitor PD407824 to enhance the retinal differentiation success in the method of Kuwahara et al. Since the method of Kuwahara et al discloses cell aggregates with BMP activator, the improved outcomes of a similar method with the inclusion of the CHK1 inhibitor PD407824, which has been established to synergize BMP, would have results that are expected based on the state of the art at the time of the application. Thus, the results as stated by Applicants, are expected, not unexpected.
In regard to claims 10-15, applicants argue that Kuwahara et al does not teach or suggest a distinct multilayer structure in which the RPE layer is on the outside side and the neural retina (NR) layer located on the inner side, and the NR layer is folded inside the aggregate, as set forth by the claims.
This argument is not found to be persuasive.
As set forth in the previous office action, Kuwahara et al does teach a multilayer cell aggregate from the method (See, p9 of Office Action dated 05/13/2026). Kuwahara et al teaches and depicts in the figures the folded inner structure of the cell aggregate (See, Figures 5-7).
Therefore, the rejections of claims 1-15 over Kuwahara et al in view of Feng et al and evidenced by Rowan et al are maintained.
RE: Nonstatutory Double Patenting over claims 23,43-45, and 47 of US Patent No. 11,214,772 B2 in view of Feng et al (Cell Reports, 2016):
Applicants traverse the nonstatutory double patenting on the grounds that one of ordinary skill in the art would have no reasonable expectation of success in including CHK1 inhibitor in a method for production of retinal cell or tissue, as set forth in the claims.
This argument is not found to be persuasive.
As discussed above, Feng et al does provide sufficient motivation for the inclusion of the CHK1 inhibitor in a method that uses BMP for retinal cell or tissue differentiation as taught by Kuwahara et al.
Therefore, the nonstatutory double patenting previously set forth is maintained.
Maintained Rejections
Claim Rejections - 35 USC § 103
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.
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 1-15 are rejected under 35 U.S.C. 103 as being unpatentable over Kuwahara et al (US 2017/0313981 A1) and in view of Feng et al (Cell Reports, 2016; as cited in IDS filed on 12/05/2023); evidenced by Rowan et al (Development,2004).
Kuwahara et al disclosed a method for producing retinal cells or retinal tissue by culturing human pluripotent stem cells (hiPScs) in suspension with sonic hedgehog activator and BMP activator (See, Abstract).
Regarding claim 1 and 4, Kuwahara et al disclosed the method for producing retinal cells/tissue comprising 3 steps. This reads on, a method for producing a retinal cell or retinal tissue comprising….
(1) is culturing the hiPScs in absence of feeder cells and in a medium to maintain pluripotency.
(2) is taking the suspension of cells from step (1) and culturing them with sonic hedgehog signal transduction pathway activator to form a cell aggregate, this reads on, …(A) suspension culturing a pluripotent stem cell to form a cell aggregate of pluripotent stem cells.
(3) is taking the cell aggregate from step (2) and culturing the cell aggregates in suspension with BMP transduction signal pathway activator to differentiate the cell aggregate to contain retinal cells or retinal tissue (See, ¶0019). This reads on, (B) suspension culturing the cell aggregate from step (A) in the presence of BMP signaling pathway agonist…to obtain a cell aggregate containing a retinal cell.
Kuwahara et al does not teach the addition of CHK1 signaling pathway inhibitor with BMP signaling pathway agonist.
Feng et al teaches that compound PD407824, a chk1 inhibitor, increases the sensitivity of cells exposed to BMP4 (See, Abstract). Feng et al teach that in human embryonic stem cells (hESCs) BMP4 is widely used for differentiation (See, p2066 col 1 paragraph 2).
Feng et al teach that in stem cell biology, CHK1 inhibitors can be a useful tool for modulating stem cell or progenitor cell fate by way of BMP signaling (See, p2073) and that concentrations of chk1 inhibitors need to be optimized, depending on the protocol and medium used (See, p2073 col 1).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of Kuwahara et al to include a CHK1 inhibitor, such as PD407824, with BMP agonist as taught by Feng et al. This reads on, wherein the CHK1 signaling pathway inhibitor is PD407824 of claim 4. This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated to make this modification because it would be advantageous to include the PD407824 in the culturing taught by Kuwahara et al, as Feng et al teaches that BMP4, a BMP agonist, is widely used in cell differentiation and PD407824 enhances its effects by inhibiting CHK1 signaling. As BMP plays a key role in retinal cell/tissue differentiation, enhancing its efficacy would be beneficial. One would have had a reasonable expectation of success due to the success of the method of Kuwahara et al and the increased sensitivity of cells exposed to BMP4 when cultured with PD407824 in Feng et al.
Regarding claim 2, following the discussion above, example 4 of Kuwahara et al disclosed that on day 18 of the method the spherical cell aggregates are fixed, cryosectioned, and immunostained to show that the cells express Chx10 (See, ¶0272-0279).
Rowan et al teaches that expression of Chx10 is sufficient to repress expression of RPE genes, concluded by expressing chick Chx10 in in a developing embryo, which resulted in downregulation of RPE markers in eyes, Mtif and Tfec (See, p5148 col 1 paragraph 2, Figure 6).
The expression of Chx10 in the cell aggregates is a known suppressor of retinal pigment epithelial (RPE) genes and differentiation, evidenced by Rowan et al. Therefore, the expression of Chx10 is known in the art to repress the expression of RPE genes, and this all reads on, wherein step (B), the BMP signaling pathway agonist is present…..that an almost truly spherical cell aggregate is formed and differentiation into a retinal pigment epithelial cell (RPE) is suppressed.
Regarding claim 3, following the discussion above, Kuwahara et al disclosed that retinal tissue means a tissue with one type or at least two or more cell types such as, photoreceptor cells, rod photoreceptors, photoceptor precursor cells, cone photoreceptor cells, retinal pigment epithelial cell (RPE), ciliary marginal zone cell (See, ¶0086). Further disclosed the retinal tissue has the cell types that constitute respective retinal layers in retina in vivo (See, ¶0086). This reads on, where the cell aggregate…in step (B).. comprising multilayer structure…including a RPE cell and inner structure including a neural retina…
Regarding claim 5, following the discussion above, Kuwahara et al disclosed that the BMP signal pathway activating substance include, BMP2, BMP4, BMP7, GDF7, anti-BMP-receptor antibody (See, ¶0168). This reads on, wherein the BMP signaling pathway agonist is one or more proteins… BMP2, BMP4. BMP7, and GDF7.
Regarding claim 6, following the discussion above, example 4 of Kuwahara et al disclosed following the steps of the method, the BMP4 (BMP agonist) was added to the cell aggregates from step (2) at day 3 after the start of the suspension for condition 1 (See, ¶0276). This reads on, wherein the step (B) the BMP signaling pathway agonist is added to the culture medium between Day 2 and Day 9 after the start of suspension culture in the step (A).
Regarding claim 7, following the discussion above, Feng et al provided motivation to have PD407824 (CHK1 inhibitor) with BMP4 together in culture to enhance the cells sensitivity to BMP agonist.
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of Kuwahara et al to include a CHK1 inhibitor, PD407824 taught by Feng et al at the simultaneously with the BMP agonist. This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated to make this modification because it would be advantageous to include the PD407824 in the culturing taught by Kuwahara et al, as Feng et al teaches that BMP4, a BMP agonist, is widely used in cell differentiation and PD407824 enhances BMP’s effect on cells by inhibiting CHK1 signaling. As BMP plays a key role in retinal cell/tissue differentiation, enhancing its efficacy would be beneficial. One would have had a reasonable expectation of success due to the success of the method of Kuwahara et al and the increased sensitivity of cells exposed to BMP4 when cultured with PD407824 in Feng et al.
Regarding claim 8, following the discussion above, Kuwahara et al does not teach the concentration for CHK1 signaling pathway inhibitor.
Feng et al teaches that in stem cell biology, CHK1 inhibitors can be a useful tool for modulating stem cell or progenitor cell fate by way of BMP signaling (See, p2073) and that concentrations of chk1 inhibitors need to be optimized, depending on the protocol and medium used (See, p2073 col 1). Feng et al used PD407824 at concentrations of 0.1μM, 0.3 μM, and 1.0 μM with 3ng/mL of BMP4 for experimentation (See, p 2067 Figure 3).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of Kuwahara et al to include a CHK1 inhibitor PD407824 at concentrations of 0.1μM, 0.3 μM, and 1.0 μM as taught by Feng et al. This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated to make this modification because it would be advantageous to include the PD407824 concentrations as taught by Feng et al due to its success in cell differentiation and effects on cell sensitivity to BMP agonist BMP4. One would have had a reasonable expectation of success due to the success evidenced by Feng et al.
Regarding claim 9, following the discussion above, Kuwahara et al disclosed that the method can produce a retinal tissue that can be used as transplantation material for retinal tissue transplantation treatments (See, ¶0298).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of Kuwahara et al to further comprise dissecting the retinal tissue to size produced by the method of Kuwahara et al for transplantation. This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated by Kuwahara et al to make this modification to ensure the retinal tissue is at the appropriate size for the transplantation. One would have had reasonable expectations of success because cutting/dissecting a tissue is standard practice in the art.
Regarding claim 10, following the discussion above, Kuwahara et al disclosed that the aggregate from step (2) that was induced in step (3) (the step with BMP agonist) results in an aggregate that contains retinal cells or retinal tissue (See, ¶0161). Kuwahara et al disclosed that the aggregate from step (2) have a high ratio of spherical cells having a smooth surface, dense inside, and uncollapsed shape (See, ¶0153). This reads on, wherein the aggregate obtained in step B is sphere-like cell aggregate.
Kuwahara et al disclosed that retinal tissue means a tissue with one type or at least two or more cell types such as, photoreceptor cells, rod photoreceptors, photoceptor precursor cells, cone photoreceptor cells, retinal pigment epithelial cell (RPE), ciliary marginal zone cell (See, ¶0086). Kuwahara et al further disclosed that after the suspension culture, the aggregates can be fixed and cryosectioned to visualize the layers of the retinal tissue by immunostaining; and that the retinal tissue in the embodiment is Rx- and Chx10-positive structure (See, ¶ 0193 and Figures 5-7). This reads on, a multilayer structure of an outer structure including retinal pigment epithelial cell and an inner structure including neural retina. This also reads on, (1) neural retina layer including at least a photoreceptor layer is formed in the inner structure, and the photoreceptor layer includes one or more cells…. retinal progenitor cells, as Chx10 positive cells are retinal progenitor cells.
Kuwahara et al disclosed that the cell aggregate prepared by completing steps (A) and (B) is a retinal tissue, specifically the neural retina is present adjacent to the ciliary marginal zone-like structure in the same cell aggregate (See, ¶0221). This reads on, (2) neural retina is present in folded state in the inner structure.
Kuwahara et al further disclosed that retinal progenitor cells express Rx and Chx10, retinal layer-specific neuron express Chk10, and retinal pigment epithelium cell express RPE65 and Mitf (See, ¶0093). This reads on, (3) the retinal pigment epithelial cell in the outer structure is a RPE65+ cell, MITF-positive cell…
Kuwahara et al does not specifically say that there is a lens, vitreous body, cornea and a blood vessel, but organoids by virtue have no vasculature and Kuwahara et al does not disclose that their method differentiates the lens and without it, vitreous body is not possible because the boundary is necessary, indicating they are not present. This reads on, (4) cell aggregate is free of lens, vitreous body, a cornea, and a blood vessel.
Regarding claim 11, following the discussion above, as Kuwahara et al discloses the cell aggregates have layers of RPE cells and neural retina, the direction the basal surface of these layers of the cell aggregate is included in the rejection of claim 10 because claim 11 is a product by process claim and the cell aggregate is a sphere (See, MPEP 2113).
Regarding claim 12, following the discussion above, Kuwahara et al disclosed that retinal tissue means a tissue with one type or at least two or more cell types such as, photoreceptor cells, rod photoreceptors, photoceptor precursor cells, cone photoreceptor cells, retinal pigment epithelial cell (RPE), ciliary marginal zone cell (See, ¶0086).
Kuwahara et al disclosed that the cell aggregate of Step (1) that is then used in Step (2) for further differentiation, is formed such that an epithelium like structure (See, ¶0075). This reads on, wherein ... further connecting as an epithelium structure…. Further includes a ciliary marginal zone-like structure between the retinal pigment epithelial cell and neural retina. As Kuwahara et al disclosed the layers of the sphere cell aggregate of the invention, it is included in the rejection because the layer format is a product by process limitation (See, MPEP 2113).
Regarding claim 13, following the discussion above, Kuwahara et al also disclosed that the ciliary marginal zone cells express Rdh10 and SSEA1 (See, ¶0093). This reads on, wherein the ciliary marginal zone-like structure includes an Rdh-10 positive cell.
Regarding claim 14, following the discussion above, example 4 of Kuwahara et al disclosed that upon cryosectioning the cell aggregate after 18 days of suspension culturing of the method of the invention, the immunostaining showed to be about 40% Rx positive and that Rx was highly positive in the neural tissues (See, ¶0279). This reads on, wherein 30% or more of the inner structure constitutes a neural retina.
Regarding claim 15, following the discussion above, Kuwahara et al disclosed that the examples where the method is used to make cell aggregates of retinal cells or tissue involve using plates with small wells, such that the wells have a base area of 0.1-2.0cm2 (See, ¶0075). Given that that size of the culturing well would dictate the size of the cell aggregates, one of ordinary skill in the art could select a well size appropriate to have the cell aggregate have a diameter of 0.2mm to 2mm. As such, determining the well size to get a cell aggregate of a certain size needed for these limitations would have been a matter of routine optimization (See, MPEP 2144.05).
Therefore, claims 1-15 are rendered obvious over Kuwahara et al (US 2017/0313981 A1) and in view of Feng et al (Cell Reports, 2016); evidenced by Rowan et al (Development,2004).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1,4-7, and 9 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 23,43-45, and 47 of U.S. Patent No. 11,214,772 B2 in view of Feng et al (Cell Reports, 2016; as cited in IDS filed on 12/05/2023).
Although the claims at issue are not identical, they are not patentably distinct from each other for the following reasons:
Regrading claim 1, 4 and 7, the reference patent claim 23 recites a method for producing a retinal tissue, comprising steps (a)-(d):
Culturing human pluripotent stem cells in the absence of feeder cells and in a medium comprising factor for maintaining an undifferentiated state,
(b)…culturing cells in sonic hedgehog signal transduction pathway activating substance…..wherein the aggregates are formed….
a third step of culturing the aggregates obtained in the second step in suspension in the presence of a BMP signal transduction pathway activating substance until retinal progenitor cells appear, thereby obtaining an aggregate containing retinal progenitor cells…
a fourth step culturing the aggregates obtained in the third step in suspension in a medium free of any of sonic hedgehog signal transduction pathway activating substance, basement membrane preparation, Wnt signal transduction pathway inhibiting substance, and a TGFβ family signal transduction pathway inhibiting substance to obtain aggregates containing a retinal tissue.
Steps (a) and (b) of the reference patent read on step (A) of the instant application claim 1, such that pluripotent stem cells are cultured to form a cell aggregate. Step (c) reads on step (B) of the instant application claim 1 but the reference patent does not include the use of CHK1 inhibitor in this step.
Feng et al teaches that compound PD407824, a Chk1 inhibitor, increases the sensitivity of cells exposed to BMP4 (a BMP agonist) (See, Abstract). Feng et al teach that in human embryonic stem cells (hESCs) BMP4 is widely used for differentiation (See, p2066 col 1 paragraph 2).
Feng et al teach that in stem cell biology, CHK1 inhibitors can be a useful tool for modulating stem cell or progenitor cell fate by way of BMP signaling (See, p2073) and that concentrations of Chk1 inhibitors need to be optimized, depending on the protocol and medium used (See, p2073 col 1).
It would have been prima facie obvious to a person having ordinary skill in the art to have modified the method of the reference patent to include a CHK1 inhibitor, such as PD407824, with BMP agonist as taught by Feng et al. This conclusion of obviousness is based on teaching suggestion motivation rationale. One would have been motivated to make this modification because it would be advantageous to include the PD407824 in the culturing taught by the reference patent, as Feng et al teaches that BMP4, a BMP agonist, is widely used in cell differentiation and PD407824 enhances its effects by inhibiting CHK1 signaling. As BMP plays a key role in retinal cell/tissue differentiation, enhancing its efficacy would be beneficial. One would have had a reasonable expectation of success due to the success of the method of the reference patent and the increased sensitivity of cells exposed to BMP4 when cultured with PD407824 in Feng et al.
Therefore, reference patent claim 23 in view of Feng et al reads on the method of instant claim 1, instant claim 4; wherein the CHK1 inhibitor is PD407824, and instant claim 7; where the BMP agonist and the CHK1 inhibitor are added to the culture medium simultaneously. This renders instant claims 1,4, and 7 obvious and rejected by nonstatutory double patenting.
Regarding claim 5, reference patent claim 43 recites …method according to claim 23, wherein the BMP signal transduction pathway activating substance is one or more proteins….. BMP2, BMP4, BMP7, and GDF7. This reads on instant claim 5 and the group of potential BMP agonists for the method of the instant application.
Therefore, instant claim 5 is rendered obvious by reference claim 43 in view of Feng et al.
Regarding claim 6, reference patent claim 45 recites ..method according to claim 23, wherein the third step, the BMP signal transduction pathway activating substance is added to the culture between day 2 and day 9 after the start of the second step. This reads on instant claim 6 and the range of days which the agonist can be added to the cell aggregate culture after initiating the method.
Therefore, instant claim 6 is rendered obvious by reference claim 45 in view of Feng et al.
Regarding claim 9, reference claim 47 recites a method for producing a neural retina comprising, producing cell aggregates comprising retinal tissue by production method according to claim 23, and cutting out the retinal tissue from the cell aggregates. This reads on instant claim 9 and as it adds to the method of instant claim 1 to further comprise dissecting the retinal tissue from the cell aggregate obtained in step (B).
Therefore, instant claim 9 is rendered obvious by reference patent claim 47 in view of Feng et al.
Therefore, claims 1, 4-7, and 9 are rejected as nonstatutory double patenting over US Patent 11,214,772 B2.
New Grounds of Rejection
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 19-21 are rejected under 35 U.S.C. 103 as being unpatentable over Kuwahara et al (US 2017/0313981 A1) and in view of Feng et al (Cell Reports, 2016; as cited in IDS filed on 12/05/2023) as applied to claims 1-15 above.
The teachings of Kuwahara et al and Feng et al are set forth above and in previous office action.
Regarding claims 19 and 21, Kuwahara et al teaches in example 1, the final concentration of exogenous human recombinant BMP4 is 1.5 nM (See, ¶0261). This reads on, wherein BMP4 is present at a concentration of 0.15 nM to 1.5 nM in step (B) of claim 19. This also reads on, wherein BMP4 is present at a concentration of 0.5 nM to 1.5 nM in step (B) of claim 21.
Regarding claim 20, following the discussion above, Kuwahara et al teaches the use of BMP4 for retinal differentiation at concentration of 1.5nM. Feng et al teaches that the use of CHK1 inhibitor PD407824, with cells, makes the cells more sensitive to exogenous BMP4 to activate BMP signaling or PD407824 lowers the threshold of the required BMP4 to activate BMP signaling (See, p2065 col 1-col 2 paragraph 2).
Therefore, Feng et al provides motivation to optimize the BMP4 concentration for the method of producing retinal cells or retinal tissue. It is considered prima facie obvious to optimize the concentration of BMP4 in the claimed method that uses CHK1 inhibitor. Given that Kuwahara et al provides an optimal concentration of BMP4 for the method without the CHK1 inhibitor and Feng et al teaches that the CHK1 inhibitor allows for BMP activation with BMP4 at sub-threshold concentrations, one of ordinary skill in the art would have been able to optimize the concentration of BMP4 of the method to produce retinal cells or retinal tissue. In the case of results effective variable, the discovery of optimum concentration would be routinely optimized by one having ordinary skill in the art based on the specifics of method of Kuwahara et al and the teachings of Feng et al. As such, the concentration of BMP4 would have been a matter of routine optimization (See, MPEP 2144.05).
Therefore, claims 19-21 are rendered obvious by Kuwahara et al in view of Feng et al.
Conclusion
Applicants’ 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 Caroline M Lara whose telephone number is (571)272-4262. The examiner can normally be reached 7:00 to 4:30pm M-Th.
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/CAROLINE M LARA/Examiner, Art Unit 1633
/ALLISON M FOX/Primary Examiner, Art Unit 1633
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