DETAILED ACTION
Applicant’s amendment and Arguments/Remarks received on 05 September 2025 have been entered. Claims 1-21 were previously pending in the application. Claim 21 has been cancelled by Applicant. Claims 1-20 are currently pending in the application. Claims 1, 15, and 20 are independent claims. The following election of species remains in effect in the instant application:
1) retinal tissue unit shapes: a. hollow ovoid,
2) differentiated living human retinal cells other than retinal epithelium cells: a. rods,
3) retinal diseases: a. age-related macular degeneration.
No claims are withdrawn from examination. Claims 1-20 are currently pending and under examination in the instant application. An action on the merits follows.
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Election of Species
As noted in the prior action, Applicant indicated that the election of species was made with traverse. However, Applicant provided no arguments distinctly and specifically pointing out the supposed errors in the election requirement. As such, the election was treated as an election without traverse (see MPEP § 818.01(a)).
Applicant argues that the election was made with traverse and with a request for re-joiner of non-elected species upon allowance of claims based on the USPTO admission that claim 1 is generic as to all species in the USPTO Restriction Requirement which read in part: “upon allowance of a generic claim, applicant will be entitled to consideration of claims to additional species… Currently the following claim(s) are generic: claim 1.” [Restriction Requirement, pg. 4]. Applicant further argues that present claims are allowable, claim 1 is generic, and non-elected species are written in dependent form, requiring all limitations of the allowable claim 1, and Applicant’s election is with traverse and the USPTO must re-join non-elected species because the election is with traverse based on the USPTO admission that claim 1 is generic and encompassing all species.
However, this is not agreed.
Note that arguing that claims are allowable or that the independent claim is generic is not distinctly and specifically pointing out any supposed errors in the election requirement, as these arguments do not address errors in the restriction requirement (see MPEP § 818.01(a)). Traversal is not a requirement for a rejoinder. Applicant is entitled to consideration of claims to additional species which are written in dependent form or otherwise require all the limitations of an allowed generic claims, upon the allowance of a generic claim whether or not the species election requirement has been traversed. Further, as discussed below, independent amended generic claim 1 is not currently in condition for allowance. As such, the election of species requirement is still deemed proper and is therefore made FINAL.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/EP2020072567, filed 12 August 2020, which claims priority to FR1909155, filed 12 August 2019. Filing of a certified copy of the FR1909155, filed 11 February 2022, is acknowledged.
Thus, the earliest possible priority for the instant application is 12 August 2019.
Specification
The objection to the specification of the disclosure for the Brief Description of the Drawings does not include a description of each panel. Specifically, the brief description of Figure 6 describes panels A and B, which correspond with panel A and E in the Drawings, but does not provide individual descriptions of panels labeled B, C, or D or the Drawings and for page 27 line 22 refers to “insert E” in Figure 6, is withdrawn in view of the amendment to the specification.
37 CFR 1.121(c)
The claim amendments filed 05 September 2025 is objected to under 37 CFR 1.121(c) because Applicant’s claim listing is not in compliance with 37 CFR 1.121(c) which states that the claim listing must provide the status of all claims, that all claims being currently amended in an amendment paper shall be presented in the claim listing, indicate a status of "currently amended," and be submitted with markings to indicate the changes that have been made relative to the immediate prior version of the claims, and that the text of all pending claims not being currently amended shall be presented in the claim listing in clean version, i.e., without any markings in the presentation of text. The presentation of a clean version of any claim having the status of "original," "withdrawn" or "previously presented" will constitute an assertion that it has not been changed relative to the immediate prior version, except to omit markings that may have been present in the immediate prior version of the claims of the status of "withdrawn" or "previously presented."
Specifically, claim 16 is marked “Currently Amended” and contains markings to indicate inserted text, but omits the deleted text “characterized in that it comprises” which should be present and marked with a strikethrough. In the interests of compact prosecution, the claim listing has been entered. However, future claim listings must include the correct status of all claims, including appropriate mark-ups for changes to the claims, in order for the claim listing to meet the requirements for entry under 37 CFR 1.121(c) or a Notice of Non-Compliant Amendment will be mailed to applicant.
Claim Interpretation- 35 USC § 112(f)
The interpretation of cancelled claim 21 under 35 U.S.C. 112(f) is no longer applicable in view of the cancellation of claim 21.
Claim Rejections - 35 USC § 112(b)
The rejection of amended, original, and cancelled claims 1-21 under 35 U.S.C. 112(b) as failing to particularly point out and distinctly claim the subject matter which the inventor(s) regards as the invention for:
Claims 2-11 and 16-21 are indefinite in their recitation of the term “characterized”;
Claim 6 recites the limitation "the juxtaposed retinal pigment epithelium cells" in lines 2-3;
Claim 8 recites “ selected from rods, cones, ganglion cells, amacrine cells, bipolar cells and horizontal cells”;
Claim 9 recitation of “it contains from 10 to 100,000 retinal cells”;
Claim 10 recites, “and/or any other retinal cells” in line 3;
Claim 11 recites, “characterized in that it is encapsulated in a hydrogel capsule”;
Claim 13 recites “a retinal tissue unit for use according to claim 12”;
claim 14 recites “a retinal tissue unit for use according to claim 13”;
Claim 15 recites, “and possibly other retinal cells” in line 12 and “any other retinal cells” in line 14;
Claims 15, 17, 20 and 21 recitation of the term “capable”; and
Claim 21 recites the claim limitation “hydrogel capsule removal means”, which invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph;
is withdrawn in view of Applicant’s cancellation of claim 21 and amendments to the claims to remove “characterized” from claims 2-11 and 16-20, to remove “the juxtaposed retinal pigment epithelial cells” from claim 6, to make the list in claim 8 a proper Markush group, to clarify which cells are being limited in claim 9, to remove “and/or other retinal cells” from claim 10, to indicate in claim 11 that the unit is encapsulated in a hydrogel, to remove “for use” from claims 13 and 14, to remove “and possibly other retinal cells” from claim 15, and to remove “capable” from claims 15, 17, and 20.
Claim Rejections - 35 USC § 112(a)
The rejection of cancelled claim 21 under 35 U.S.C. 112(a) for reciting the claim limitation “hydrogel capsule removal means”, which invokes 35 U.S.C. 112(f) or pre-AIA 35 U.S.C. 112, sixth paragraph; however, the written description fails to disclose the corresponding structure, material, or acts for performing the entire claimed function and to clearly link the structure, material, or acts to the function, is withdrawn in view of Applicant’s cancellation of claim 21.
Claim Rejections - 35 USC § 101
The rejection of amended and original claims 1-3, 6-8, and 12-14 under 35 U.S.C. 101 as being directed to a product of nature without significantly more is withdrawn over amended claims 12-14 and maintained over amended and original claims 1-3 and 6-8 in view of Applicant’s amendments to claim 12-14 such that claim 12 now recites “The retinal tissue unit of claim 1” rather than merely the retinal tissue of claim 1. Applicant's amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed in detail below.
Applicant argues that the RPE cells of a human eye are present as a single cell layer in the posterior pole of an eye, and as such are not organized around an inner cavity, as depicted in Figures 1 and 6B. However, this is not agreed.
Note that Figures 1 and 6B show examples of the invention, but are not themselves limiting definitions of the invention. As discussed in the prior action, the broadest reasonable interpretation of a cell layer “organized around an inner cavity” does not require that the layer fully encompass the inner cavity. Instead, that the terms “hollow” and “inner cavity” in claim 1 have been afforded their broadest reasonable interpretations such that “hollow” refers to a cell-free space interior to the unit, and “inner cavity” refers to a space that is at least partially surrounded by the RPE cell layer. The specification does not provide a limiting definition of “organized around” or “an inner cavity” which would narrow the interpretation of these terms to indicate only a cell layer which fully encompasses an inner space in 3 dimensions such that the cell layer encompasses all surfaces of the cavity.
Further, the argument that RPE cells in a naturally occurring human eye being “present in a single-cell layer in the posterior pole” of the eye merely indicates which portion of the inner cavity surface the cells layer is organized around. As written, claim 1 encompasses an RPE layer which partially encompasses an inner cavity, and as such encompasses a natural human eye.
Therefore, Applicant’s arguments are not sufficient to overcome the rejection under 35 USC 101 over original and amended claims 1-3 and 6-8 for being directed to a product of nature, and the rejection is maintained.
Claim Rejections - 35 USC § 102
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 rejection of original and amended claims 1, 3-5, 7-9, and 12-14 under 35 U.S.C. 102(a)(1) as being anticipated by Singh et al. (2015, Stem Cell & Development, 24(23), 2778-2795), is maintained. Applicant's amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed in detail below.
Applicant amended claim 9 to recite wherein the retinal tissue unit contains from 10 to 1000,000 of the differentiated living human retinal pigment epithelium cells. Singh (2015) was cited in the prior action for teaching that the large and elongated hESC-derived retinal tissue aggregates cultured in their conditions were about 150-300 somas in diameter and 8-12 somas in thickness [column 22 ¶ 3]. Singh (2015) also teaches that a large 1 mm thick section of hESC-derived retinal tissue provides about 3200 photoreceptors, about 2000 amacrine cells, and about 3200 retinal ganglion cells, for a total of about 8400 retinal cells [column 22 ¶ 3, Figure 9]. As shown in Figure 9 of Singh (2015), the section comprising about 8400 retinal cells is cut out to comprise the long side of the organoid, such that the total organoid would comprise about 3-5x the number of cells as comprised within the section, which would indicate a total retinal cell count within the retinal tissue unit of about 25,000-42,000 retinal cells. With respect to RPE cells specifically, inspection of Figures 2 and S1 indicate a robust layer of RPE surrounding the photoreceptor layer, such that the RPE cells are fewer in number than the PR cells, and clearly greater than 10 cells/ section, which is further supported by the schematic depiction in Figure 9. As such, Singh (2015) teaches that the RPE cell count in the retinal tissue unit is between 10 and 100,000 cells.
Claim 12 was amended to recite, wherein the retinal tissue unit is implantable into the eye of a subject in need of treatment for a retinal disease. Singh (2015) teaches a retinal repair strategy using the retinal tissue unit by isolating a long piece of the retinal tissue from the retinal tissue unit for subretinal grafting [Figure 9], thereby teaching that the retinal tissue unit is implantable into the eye of a subject in need of treatment for a retinal disease.
Therefore, Applicant’s amendments to the claims have not narrowed the scope of the claims sufficiently to overcome a finding of anticipation under 35 USC 102(a)(1).
Applicant argues that:
Examiner has interpreted the terms “hollow” and “organized around an inner cavity” too broadly and inconsistently with the plain language in the claims, in that illustrations in Figure 1 and 6B provide “clear definition[s]” of the terms and that the broadest reasonable interpretation “must be consistent with the use of the claim term in the specification and drawings” [MPEP 2111];
The cross-sectional images of Singh (2015) show dense tissue aggregates without an organized internal cavity, and not hollow units with the defined architecture as presently claimed;
Examiner bases the inner cavity of Singh as being hollow based on an inference not supported by data, which in contravention to the USPTO MPEP requirements (with no specific section cited);
That the retinal tissue of present claim 1 differs from Singh by at least:
Architectural organization in that Singh describes dense tissue aggregates without the specific organization around an inner cavity as claimed, wherein the “cavities” in the images of Singh are sectioning artifacts or unorganized intercellular spaces;
Specific cellular polarization in that Singh does not clearly demonstrate the specific polarization as claimed;
Controlled dimensions and shape in that Singh describes irregular aggregates of variable sizes without specific control of hollow structures and without the specific shapes claimed of hollow ovoid, hollow cylinder, hollow spheroid, or hollow sphere; and
Singh does not describe the specific use of hollow retinal tissue units as claimed such that the therapeutic use must be based on the specific claimed structure and not on generic tissue aggregates.
However, this is not agreed.
Regarding Applicant’s argument 1), that Examiner has interpreted the terms “hollow” and “organized around an inner cavity” too broadly and inconsistently with the plain language the claims, note that while the broadest reasonable interpretation “must be consistent with the use of the claim term in the specification and drawings” [MPEP 2111], note that MPEP 2111 also states:
Under a broadest reasonable interpretation (BRI), words of the claim must be given their plain meaning, unless such meaning is inconsistent with the specification. The plain meaning of a term means the ordinary and customary meaning given to the term by those of ordinary skill in the art at the relevant time. The ordinary and customary meaning of a term may be evidenced by a variety of sources, including the words of the claims themselves, the specification, drawings, and prior art. However, the best source for determining the meaning of a claim term is the specification - the greatest clarity is obtained when the specification serves as a glossary for the claim terms. … The words of the claim must be given their plain meaning unless the plain meaning is inconsistent with the specification… Ordinary, simple English words whose meaning is clear and unquestionable, absent any indication that their use in a particular context changes their meaning, are construed to mean exactly what they say. … (citations omitted).
The presumption that a term is given its ordinary and customary meaning may be rebutted by the applicant by clearly setting forth a different definition of the term in the specification. In re Morris, 127 F.3d 1048, 1054, 44 USPQ2d 1023, 1028 (Fed. Cir. 1997) (the USPTO looks to the ordinary use of the claim terms taking into account definitions or other "enlightenment" contained in the written description); But c.f. In re Am. Acad. of Sci. Tech. Ctr., 367 F.3d 1359, 1369, 70 USPQ2d 1827, 1834 (Fed. Cir. 2004) ("We have cautioned against reading limitations into a claim from the preferred embodiment described in the specification, even if it is the only embodiment described, absent clear disclaimer in the specification."). When the specification sets a clear path to the claim language, the scope of the claims is more easily determined and the public notice function of the claims is best served. [MPEP 2111.01(I)].
Additionally, MPEP 2111.01(II) further states, "Though understanding the claim language may be aided by explanations contained in the written description, it is important not to import into a claim limitations that are not part of the claim. For example, a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment."
In the instant case, Applicant has not clearly set forth a limiting definition of the terms “hollow”, or “inner cavity” which would differentiate the terms from the broadest reasonable interpretation based on the plain meaning of the words as presented by the Examiner in the prior action: “Note that the terms ‘hollow’ and ‘inner cavity’ in claim 1 have been afforded their broadest reasonable interpretations such that ‘hollow’ refers to a cell-free space interior to the unit, and ‘inner cavity’ refers to a space that is at least partially surrounded by the RPE cell layer.” [ page 16].
Applicant argues that the illustration presented in Figure 1, which is a sketch of two concentric round lines, along with the image in Figure 6B, which is a fluorescent image of a cross section of a unit of the invention provide limiting definitions for the terms “hollow” and “inner cavity”. However, the Brief Description of the Figures merely states that “figure 1 is a schematic representation of a cross-sectional view of a tissue unit 10 according to the invention, with a retinal pigment epithelium layer 12 and an inner cavity 14, with A corresponding to the apical side of the retinal pigment epithelium cells and B corresponding to the basal side of the retinal pigment epithelium cells.” [page 7]. The Brief Description of the Figures also states that “Figure 6A-6E are microscopy images of hydrogel (alginate) microcompartments. A hydrogel microcompartment encapsulating a small tissue unit according to the invention is shown in Figure 6A, DAPI staining is shown in Figure 6B” [page 8]. As disclosed, figures 1 and 6B present non-limiting examples of the tissue unit, and do not present limiting definitions for descriptive terms. As presented above, the MPEP requires that a particular embodiment appearing in the written description may not be read into a claim when the claim language is broader than the embodiment.
Nothing in the specification provides a limiting definition for “hollow” nor for “inner cavity” to differentiate them from the BRIs presented in the prior action, which are consistent with the plain language recited in the claims and also consistent with the use of the terms in the specification, while not inappropriately importing limitations from non-limiting teachings of specific examples in the disclosure.
Regarding argument 2), that the cross-sectional images of Singh (2015) show dense tissue aggregates without an organized internal cavity, and not hollow units with the defined architecture as presently claimed, note that the present claims as written do not recite an organized internal cavity. The claims as written recite that the cells are organized around an inner cavity. Additionally, claim 1 recites that the retinal tissue unit is hollow, which precludes organization of the cavity itself.
The structures of Singh (2015) clearly demonstrate at least one layer of differentiated living human retinal pigment epithelial cells which themselves have an organized structure [Figure 2, 9]. Additionally, as discussed in the prior action, although Singh (2015) does not explicitly teach that the inner cavity of the retinal tissue unit is “hollow”, multiple cross section images of the retinal tissue units depict structures which are curved around an inner cell-free cavity (see e.g., Figures 2, 5, 6, 7, and S1). Additionally, Figure 9 illustrates that the RPE layer curves around an inner cavity. As such, Singh implicitly teaches that the structure are hollow, which is supported by the Figures presented in Singh (2015) and is not merely an inference unsupported by the data.
Note also that the “defined architecture” as presently claimed is recited broadly such that claim 1 merely requires that a layer of living human RPE cells are organized around any inner cavity with the basal side of each RPE cell pointing outwards and the apical side of the cell pointing towards the inner cavity. Further, as discussed in the prior action, Singh (2015) teaches that the basal side of each RPE cell is pointing outwards (e.g., away from the inner cavity) and the apical side is pointing towards the inner cavity [column 19 ¶ 1, Figure 2, 9, S1, S7]. As such, the retinal units of Singh (2015) meet the claim limitations, including the claimed architecture, as currently recited.
Regarding argument 3), that Examiner bases the inner cavity of Singh as being hollow based on an inference not supported by data, which in contravention to the USPTO MPEP requirements, as discussed above, although Singh (2015) does not explicitly teach that the inner cavity of the retinal tissue unit is “hollow”, multiple cross section images of the retinal tissue units depict structures which are curved around an inner cell-free cavity (see e.g., Figures 2, 5, 6, 7, and S1). Additionally, Figure 9 illustrates that the RPE layer curves around an inner cavity. As such, Singh implicitly teaches that the structure are hollow, which is supported by the Figures presented in Singh (2015) and is not merely an inference unsupported by the data.
Regarding argument 4a), that the architectural organization of Singh (2015) differs from the present claims in that Singh (2015) describes dense tissue aggregates without the specific organization around an inner cavity as claimed, wherein the “cavities” in the images of Singh are sectioning artifacts or unorganized intercellular spaces, as discussed above, multiple cross section images of the retinal tissue units depict structures which are curved around an inner cell-free cavity (see e.g., Figures 2, 5, 6, 7, and S1-S7). Additionally, Figure 9 illustrates that the RPE layer curves around an inner cavity. Again, note that the cavity itself is not claimed to be organized. The cross sections of the organoids taught by Singh (2015) clearly teach hollow cavities around which the RPE and other retinal cells are organized [Figure 2-7, S4-S7]. Additionally, the multiple figures of Singh (2015) show clear layering of the retinal cells, demonstrating architectural organization of the cells surrounding the inner cell-free cavities [Figures 2-7, S1-S10].
Regarding argument 4b), that the specific cellular polarization in that Singh does not clearly demonstrate the specific polarization as claimed, as discussed in the prior action and above, Singh (2015) teaches a three-dimensional (3D) retinal tissue unit/organoid comprising at least one layer of differentiated living human pigment epithelium (RPE) cells organized around an inner cavity, with the basal side of each RPE cell pointing outwards (e.g., away from the inner cavity) and the apical side pointing towards the inner cavity [column 19 ¶ 1, Figure 2, 9, S1, S7].
Additionally, Singh (2015) teaches that photoreceptors (PRs) and RPE interact functionally and structurally to polarize each other [column 1 ¶ 1], and that the retinal units they produce comprise both PRs and RPE, wherein the RPE and PRs are adjacent layers [abstract, column 8 ¶ 4, Figure 2, 9, S1, S7]. Singh (2015) further teaches that the apical side of RPE cells is the side which interacts with PRs by teaching that the development of PR outer segments requires a mature RPE with apical microvilli, and Figure 9 illustrates the microvilli as being on the inner-pointing surface of the RPE [column 20 ¶ 3, Figure 9]. Therefore, given that the RPE are the outer layer (seen in Figure 2), the PRs are the next inner layer [abstract, Figure 2, 9, S1], then the apical side of the RPE (photoreceptor-interacting side) is pointing inward toward the cavity, and as such the basal side is pointing outward away from the cavity, as illustrated in Figure 9.
Regarding argument 4c), that the present claims differ from Singh (2015) in controlled dimensions and shape in that Singh describes irregular aggregates of variable sizes without specific control of hollow structures and without the specific shapes claimed of hollow ovoid, hollow cylinder, hollow spheroid, or hollow sphere, note that, as discussed in the prior action, the term “ovoid” in claim 3 has been afforded its broadest reasonable interpretation to refer to any 3D structure which is generally round but not a perfect sphere. The retinal tissue organoids of Singh (2015) are three-dimensional structures which are generally round, but not perfectly sphere [Figures 2-7, 9, S1-S2, S4-S10], and as such, the retinal tissue organoids of Singh (2015) are in the form of hollow ovoids.
Note also that the claims as written do not required “controlled dimensions”, merely that the units fall within the recited dimensional length limitations. The cross section image in Singh (2015) Figure 3a displays a full cross section, indicating that the larger dimension is approximately 200 µm (e.g., between 100 and 1,000 µm) and the shorter dimension is approximately 150 µm (e.g., between 10 and 1,000 µm). Additionally, Figure S4 shows a cross section wherein the retinal tissue is about 125 µm x 100 µm.
Regarding argument 4d), that Singh (2015) does not describe the specific use of hollow retinal tissue units as claimed such that the therapeutic use must be based on the specific claimed structure and not on generic tissue aggregates, note that as discussed above, Singh (2015) teaches hollow 3D retinal tissue structures which are encompassed by the instant claims as written. ]. Singh (2015) also teaches a retinal repair strategy using hESC-derived retinal tissue [Figure 9], and that they project from their findings that their hESC-derived retinal tissue would be able to synapse with the RGCs of the recipient retina in subretinal grafts, such that transplantation of hPSC-derived retinal tissue is a promising approach to repair vision [column 22 ¶ 2]. As such, Singh (2015) teaches that the retinal tissue is suitable for use in the treatment of a retinal disease, including age-related macular degeneration. As such, the teachings of Singh (2015) that the tissue structures are implantable into the eye of a subject in need of treatment for a retinal disease, such as age-related macular degeneration, meets the claim requirements for claims 12-14 as written.
Accordingly, Applicant’s amendments and arguments do not overcome a finding of anticipation by Singh (2015) under 35 USC 102(a)(1), and the rejection is maintained.
Claim Rejections - 35 USC § 103
The rejection of original, amended, and cancelled claims 1-21 under 35 U.S.C. 103 as being unpatentable over Singh et al. (2015, Stem Cell & Development, 24(23), 2778-2795); in view of Feyeux (WO2018096277A1, published 31 May 2018, IDS, English translation from PE2E); Singh et al. (2018, Stem Cell Reviews & Reports, 14, 463-483); Rizzolo et al. (2011, Progress in Retinal & Eye Research, 30, 296-323); and Singh et al. (2019, Stem Cells & Development, 28(17), 1151-1166, published 18 June 2019) is withdrawn over cancelled claim 21 and maintained over original and amended claims 1-20 in view of Applicant’s cancellation of claim 21. Applicant's amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed in detail below.
Applicant amended claim 9 to recite wherein the retinal tissue unit contains from 10 to 1000,000 of the differentiated living human retinal pigment epithelium cells. Singh (2015) was cited in the prior action for teaching that the large and elongated hESC-derived retinal tissue aggregates cultured in their conditions were about 150-300 somas in diameter and 8-12 somas in thickness [column 22 ¶ 3]. Singh (2015) also teaches that a large 1 mm thick section of hESC-derived retinal tissue provides about 3200 photoreceptors, about 2000 amacrine cells, and about 3200 retinal ganglion cells, for a total of about 8400 retinal cells [column 22 ¶ 3, Figure 9]. As shown in Figure 9 of Singh (2015), the section comprising about 8400 retinal cells is cut out to comprise the long side of the organoid, such that the total organoid would comprise about 3-5x the number of cells as comprised within the section, which would indicate a total retinal cell count within the retinal tissue unit of about 25,000-42,000 retinal cells. With respect to RPE cells specifically, inspection of Figures 2 and S1 indicate a robust layer of RPE surrounding the photoreceptor layer, such that the RPE cells are fewer in number than the PR cells, and clearly greater than 10 cells/ section, which is further supported by the schematic depiction in Figure 9. As such, Singh (2015) teaches that the RPE cell count in the retinal tissue unit is between 10 and 100,000 cells.
Claim 12 was amended to recite, wherein the retinal tissue unit is implantable into the eye of a subject in need of treatment for a retinal disease. Singh (2015) teaches retinal a repair strategy using the retinal tissue unit by isolating a long piece of the retinal tissue from the retinal tissue unit for subretinal grafting [Figure 9], thereby teaching that the retinal tissue unit is implantable into the eye of a subject in need of treatment for a retinal disease. Additionally, Singh (2019) teaches the implantation of organoids into the eye of a subject, demonstrating implantation in a wild-type cat eye and teaching that transplanting retinal tissue in degenerating cat retina will enable rapid development of preclinical in vivo work focused on vision restoration, thereby also teaching implantation of the retinal tissue units into the eye of a subject in need of treatment for a retinal disease [abstract].
Therefore, Applicant’s amendments to the claims have not narrowed the scope of the claims sufficiently to overcome a finding of obviousness under 35 USC 103.
Applicant argues that:
Singh (2015) fails to disclose or even reasonably suggest several claimed elements, as discussed in connect with the anticipation rejection;
The combined references do not teach the claimed hollow structure, in that:
Singh (2015) discloses dense tissue aggregates without organized hollow architecture, and
Feyeux discloses generic microcompartments with cells surrounding a lumen, not specifically organized retinal tissue units;
Examiner improperly combines references from unrelated technical fields without adequate motivation, wherein the references provide contradictory technical approaches, such that the Examiner’s combination relies on impermissible hindsight reasoning
The cited reference combination fails to teach:
Specific polarization of RPE cells (basal outward, apical side toward cavity),
Controlled hollow geometry (ovoid, cylinder, spheroid, sphere),
Organized architecture around a defined inner cavity, and
Integration of extracellular matrix on the basal side of RPE cells;
The office cannot establish reasonable expectation of success because combining Feyeux’s pluripotent cell maintenance system with Singh’s differentiated retinal tissue approach would not provide a reasonable expectation of success because the technical requirements are fundamentally different in that Feyeux requires maintaining undifferentiated state whereas Singh 2015 requires differentiation into retinal tissue;
The specific hollow architecture as presently claimed would not be expected from combining the cited references, such that the claimed retinal tissue units include unexpected technical advantages not taught by the prior art, including:
Enhanced integration in that the specific polarization allows proper integration with host retinal tissue,
Improved survival in that the hollow structure facilitates nutrient diffusion and waste removal,
Controlled geometry in that precise dimensional control enables predictable therapeutic outcomes, which contribute to
Unexpected therapeutic benefits not achievable with the dense aggregates of Singh (2015) or the generic microcompartments of Feyeux;
Neither Singh (2015) nor Feyeux teaches the specific placement of extracellular matrix on the basal side of RPE cells in a hollow retinal tissue unit;
Regarding claims 15-21, the combined references do not teach the specific method steps of:
Producing cellular microcompartments with the claimed specific structure
Removing hydrogel capsules to recover hollow 3D retinal tissue units, or
Loading into surgical implantation devices suitable for eye injection,
Singh 2015 does not teach:
kits specifically for hollow retinal tissue units,
hydrogel capsule removal means as a kit component, or
integration of all claimed kit elements; and
the specific hollow architecture as presently claimed addresses previously unsolved problems in retinal tissue engineering, such that the specific structural features claimed represent a significant advance in retinal tissue engineering by addressing critical limitation of prior approaches.
However, this is not agreed.
In response to applicant’s arguments against the references individually, it is noted that the test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). Further, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007). In addition, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Specifically, regarding argument 1), that Singh (2015) fails to disclose or even reasonably suggest several claimed elements, as discussed in connect with the anticipation rejection, note that, as discussed above, Applicant’s amendments and arguments do not overcome a finding of anticipation by Singh (2015) for original and amended claims 1, 3-5, 7-9, and 12-14.
Regarding argument 2), that the combined references do not teach the claimed hollow structure, in that a) Singh (2015) discloses dense tissue aggregates without organized hollow architecture, and b) Feyeux discloses generic microcompartments with cells surrounding a lumen, not specifically organized retinal tissue units, note that Singh (2015) discloses retinal tissue structure which meet the claimed limitations for original and amended claims 1, 3-5, 7-9, and 12-14.
As discussed above, the structures of Singh (2015) clearly demonstrate at least one layer of differentiated living human retinal pigment epithelial cells which themselves have an organized structure [Figure 2, 9]. Singh also teaches that the structure are hollow, which is supported by the Figures presented in Singh (2015). Further, as discussed in the prior action, Singh (2015) teaches that the basal side of each RPE cell is pointing outwards (e.g., away from the inner cavity) and the apical side is pointing towards the inner cavity [column 19 ¶ 1, Figure 2, 9, S1, S7]. As such, the retinal units of Singh (2015) meet the claim limitations, including the claimed architecture, as currently recited.
Additionally, Feyeux was cited for teaching a cellular microcompartment or capsule comprising a hydrogel shell, an extracellular matrix (ECM) layer, and one or more layers of human pluripotent cells surrounding a central lumen, such that the ECM is on the “outside” of the cell layer [page 4 ¶ 7]. Feyeux additionally teaches that the microcompartments make it possible to cultivate the cells in a liquid medium, using the media conventionally used in 2D culture, while protecting the cells from mechanical stress and controlling their phenotype to avoid wild differentiations and to maintain pluripotency [page 4 ¶ 7]. Although Feyeux teaches the use of the microcompartments specifically for maintaining pluripotency, an ordinarily skilled artisan would understand that the teachings by Feyeux that the microcompartments allow the culture of cells while protecting the cells and controlling their phenotype would be applicable to other cell types for which a phenotype is desired to be maintained. Feyeux also teaches that the cells can be differentiated before use directly in the microcompartment [page 4 ¶ 7- page 5 ¶ 1], thereby teaching a microcompartment comprising differentiated cells, and not solely pluripotent cells. Feyeux also teaches that the extracellular matrix layer is necessary for the survival of pluripotent cells in the microcompartment and the creation of the closed hollow structure in an elongate (e.g., ovoid or tubular) shape [page 6 ¶ 6, page 7 ¶ 2-3, 6]. As such, an ordinarily skilled artisan would have been motivated to use the ovoid microcompartments of Feyeux, including a hydrogel shell and an extracellular matrix, for producing hollow 3D differentiated tissue structures to allow survival of the cells and the creation of the hollow structure while also protecting the cells and controlling their phenotype.
Regarding argument 3), that the Examiner improperly combined references from unrelated technical fields without adequate motivation, wherein the references provide contradictory technical approaches, such that the Examiner’s combination relies on impermissible hindsight reasoning, note that claiming that Feyeux is an unrelated technical field is a mischaracterization of Feyeux. Feyeux teaches the culture and differentiation of iPSCs within the microcompartments. The retinal cells of the instant application are recited in claim 10 to be differentiated from induced pluripotent stem cells (iPSCs). Accordingly, Feyeux represents art which is in a closely related technical field.
Regarding argument 4), that the cited reference combination fails to teach (a) specific polarization of RPE cells (basal outward, apical side toward cavity), (b) controlled hollow geometry (ovoid, cylinder, spheroid, sphere), (c) organized architecture around a defined inner cavity, and (d) integration of extracellular matrix on the basal side of RPE cells, note that Singh (2015) teaches each of (a)-(c), as discussed above in response to arguments against the anticipation rejection.
Further, Feyeux teaches that the extracellular matrix layer is necessary for the survival of pluripotent cells in the microcompartment and the creation of the closed hollow structure in an elongate (e.g., ovoid or tubular) shape [page 6 ¶ 6, page 7 ¶ 2-3, 6]. Feyeux teaches a cellular microcompartment or capsule comprising a hydrogel shell, an extracellular matrix (ECM) layer, and one or more layers of human pluripotent cells surrounding a central lumen, such that the ECM is on the “outside” of the cell layer [page 4 ¶ 7]. Singh (2015) teaches that the basal side of the RPE cells is pointing outwards. Therefore, the teaching of Feyeux to generate an ECM layer outside of the cell layer, when combined with the retinal cell structure taught by Singh (2015), is a teaching that the ECM layer is on the basal side of the RPE, and an ordinarily skilled artisan when considering the teachings of Feyeux, would be motivated to include the ECM layer on the outside of the cell layer to support the survival of the cells in the microcompartment.
Regarding argument 5), that the office cannot establish reasonable expectation of success because combining Feyeux’s pluripotent cell maintenance system with Singh’s differentiated retinal tissue approach would not provide a reasonable expectation of success because the technical requirements are fundamentally different in that Feyeux requires maintaining undifferentiated state whereas Singh 2015 requires differentiation into retinal tissue, note that although Feyeux teaches maintaining an undifferentiated state, Feyeux does not require the maintenance of an undifferentiated state. As discussed above, Feyeux also teaches that the cells can be differentiated before use directly in the microcompartment [page 4 ¶ 7- page 5 ¶ 1]. As such, the technical requirements of Singh 2015 and Feyeux are not fundamentally different so as to be incompatible.
Regarding argument 6), that the specific hollow architecture as presently claimed would not be expected from combining the cited references, note that as discussed above, the combination of Singh (2015), Feyeux, Singh (2018), Rizzolo, and Singh (2019) provide the teachings and motivation for retinal tissue units having the hollow architecture presently claimed.
Applicant argues that that the claimed retinal tissue units include unexpected technical advantages not taught by the prior art, including: (a) enhanced integration in that the specific polarization allows proper integration with host retinal tissue, improved survival in that the hollow structure facilitates nutrient diffusion and waste removal, (b) controlled geometry in that precise dimensional control enables predictable therapeutic outcomes, which contribute to (c) unexpected therapeutic benefits not achievable with the dense aggregates of Singh (2015) or the generic microcompartments of Feyeux.
Note that although Applicant generically states, “as shown in the specification”, Applicant has not provided nor pointed to any specific evidence to support a claim of unexpected results. As such, Applicant’s arguments amount to arguments of counsel. The arguments of counsel cannot take the place of evidence in the record. In re Schulze, 346 F.2d 600, 602, 145 USPQ 716, 718 (CCPA 1965); In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997) ("An assertion of what seems to follow from common experience is just attorney argument and not the kind of factual evidence that is required to rebut a prima facie case of obviousness."). See MPEP § 716.01(c) for examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration. Examples of attorney statements which are not evidence and which must be supported by an appropriate affidavit or declaration include statements regarding unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the applicant. MPEP 716.01(c).
Attorney argument is not evidence unless it is an admission, in which case, an examiner may use the admission in making a rejection. See MPEP § 2129 and § 2144.03 for a discussion of admissions as prior art.
It is also noted that any evidence of unexpected results must be commensurate in scope with the claimed invention, and that a greater, or greater than additive, effect is not necessarily sufficient to overcome a prima facie case of obviousness because such an effect can either be expected or unexpected MPEP 716.02 (a) and (d). Whether the unexpected results are the result of unexpectedly improved results or a property not taught by the prior art, the "objective evidence of nonobviousness must be commensurate in scope with the claims which the evidence is offered to support." In other words, the showing of unexpected results must be reviewed to see if the results occur over the entire claimed range. In re Clemens, 622 F.2d 1029, 1036, 206 USPQ 289, 296 (CCPA 1980). In the instant case, Applicant has not provided any evidence of unexpected results. As such, the evidence is not commensurate in scope with the claimed invention.
Further, to the extent that Figures 5-9 are meant to support the assertion of unexpected structural advantages, note that, as discussed above and further in detail below, the combination of Singh (2015), Feyeux, Singh (2018), Rizzolo, and Singh (2019) provide the teachings and motivation for retinal tissue units having the hollow architecture presently encompassed by the presently recited claims as written. Accordingly, any unexpectedly advantageous structure presumed to be taught by the instant disclosure is not commensurate in scope with the instant claims, if indeed such a difference between the cited art and the instant disclosure exists.
Additionally, regarding Applicant’s assertion that the specific structural features provide unexpected therapeutic benefits, it is further noted that Applicant has not provided any evidence of unexpected therapeutic benefits. None of the data provided in the specification nor the drawings provide any teachings for any therapeutic benefit. The figures of the drawings are all directed to structural features of the retinal tissue units. The specification merely teaches the aspiration of using the retinal tissue units for therapeutic applications [page 2 line 32 – page 3 line 30, page 24 line 24 - page 26 line 9]. The specification provides no examples with data for any therapeutic benefit.
Therefore, Applicant has not provided any support for a finding of unexpected results.
Regarding argument 7), that neither Singh (2015) nor Feyeux teaches the specific placement of extracellular matrix on the basal side of RPE cells in a hollow retinal tissue unit, as discussed above, Feyeux teaches a cellular microcompartment or capsule comprising a hydrogel shell, an extracellular matrix (ECM) layer, and one or more layers of human pluripotent cells surrounding a central lumen, such that the ECM is on the “outside” of the cell layer [page 4 ¶ 7]. Singh (2015) teaches that the basal side of the RPE cells is pointing outwards. Therefore, the teaching of Feyeux to generate an ECM layer outside of the cell layer, when combined with the retinal cell structure taught by Singh (2015), is a teaching that the ECM layer is on the basal side of the RPE, and an ordinarily skilled artisan when considering the teachings of Feyeux, would be motivated to include the ECM layer on the outside of the cell layer (e.g., on the basal side of the RPE layer) to support the survival of the cells in the microcompartment.
Regarding argument 8), that the combined references do not teach the specific method steps of (a) producing cellular microcompartments with the claimed specific structure, (b) removing hydrogel capsules to recover hollow 3D retinal tissue units, or (c) loading into surgical implantation devices suitable for eye injection, note that the term “microcompartment” has not been defined in the claim and further does not have a limiting definition within the specification. As such, the term “microcompartment” has been afforded its broadest reasonable interpretation of any space and/or structure which holds cells capable of differentiating into at least RPE cells and/or differentiated RPE cells.
Singh (2015) was cited for teaching a method for preparing a retinal tissue unit as described above, comprising producing a cellular microcompartment comprising cells capable of differentiating into at least RPE cells (e.g., hESCs) within a hydrogel (e.g., Matrigel®) and inducing cell differentiation with in the cellular microcompartment so as to obtain RPE cells and other retinal cells for further processing/ testing [column 4 ¶ 1, Figure S1]. Singh (2015) also teaches removing the hydrogel to recover the ROE cells and other retinal cells in the form of a hollow 3D retinal tissue unit [column 5 ¶ 2-3, column 6 ¶ 2, column 7 ¶ 2, column 23 ¶ 2].
Feyeux was cited for teaching a cellular microcompartment or capsule comprising a hydrogel shell, an extracellular matrix (ECM) layer, and one or more layers of human pluripotent cells surrounding a central lumen, such that the ECM is on the “outside” of the cell layer [page 4 ¶ 7]. Feyeux teaches a method for preparing a tissue unit comprising the steps of a) producing a cellular microcompartment comprising an extracellular matrix and cells capable a differentiating into at least RPE cells (e.g., IPSC, ESCs), wherein the ECM and cells are comprised within a hydrogel capsule [page 8 ¶ 1-3]; b) inducing cell differentiation within the cellular microcompartment to obtain one or more cell types of interest as a 3D cellular network [page 10 ¶ 5]; and c) removing the hydrogel capsules to recover the differentiated cells in the form of a hollow 3D tissue unit [page 8 ¶ 3, page 10 ¶ 5]. Feyeux additionally teaches that the microcompartments make it possible to cultivate the cells in a liquid medium, using the media conventionally used in 2D culture, while protecting the cells and controlling their phenotype to avoid wild differentiations and to maintain pluripotency [page 4 ¶ 7]. Feyeux also teaches that the extracellular matrix layer is necessary for the survival of pluripotent cells in the microcompartment and the creation of the closed hollow structure in an elongate (e.g., ovoid or tubular) shape [page 6 ¶ 6, page 7 ¶ 2-3, 6]. Feyeux further teaches that the hydrogel shell protects the cells from mechanical stress associated with collisions or fusions during the culture in liquid suspension [page 4 ¶ 7]. Feyeux also teaches that the cells can be differentiated before use directly in the microcompartment [page 4 ¶ 7- page 5 ¶ 1]. As such, an ordinarily skilled artisan would have been motivated to use the method of Feyeux, for preparing a retinal tissue unit, such as the retinal tissue of Singh differentiated from human pluripotent stem cells.
Singh (2019) was cited for teaching a method of transplanting stem cell-derived retinal tissue into the subretinal space of a large-eye animal model [abstract]. Singh (2019) teaches differentiating hESCs into 3D retinal tissue units/organoids comprising 3D retina surrounded by brown RPE cells [column 4 ¶ 3]. Singh (2019) also teaches the subretinal transplantation of retinal organoids comprising loading organoids into an organoid glass injection cannula and injecting the organoids into the subretinal space [column 5 ¶ 4- column 6 ¶ 1]. Accordingly, the organoid glass injection cannula taught by Singh is a surgical implantation device suitable for injection into the eye. Singh (2019) further teaches that the procedure used for grafting hESC-derived retinal tissue from organoids into the subretinal space of the cat eye provided very promising outcomes of grafting, such as demonstrating robust survival and axonal connectivity for both graft to host and host to graft, such that the work provides a foundation for developing retinal and vision restoration technologies in a large-eye model which is relevant to human therapies [column 14 ¶ 2]. Therefore, an ordinarily skilled artisan at the time of filing the instant application would have been motivated to use the method of grafting taught by Singh (2019), including the surgical implantation device, in a method of preparing a retinal tissue unit and implanting it into an eye for achieving robust survival and axonal connectivity for the grafted cells.
Accordingly, the cited references teach the specific method steps of (a) producing cellular microcompartments with the claimed specific structure, (b) removing hydrogel capsules to recover hollow 3D retinal tissue units, or (c) loading into surgical implantation devices suitable for eye injection.
Regarding argument 9), that Singh 2015 does not teach (a) kits specifically for hollow retinal tissue units, (b) hydrogel capsule removal means as a kit component, or (c) integration of all claimed kit elements, note firstly that a hydrogel capsule removal means is no longer recited in the pending claims. Additionally, note that the specification, however, does not define the term “kit”, and so it is being interpreted to encompass any collection of reagents that includes all of the elements of the claims. Any further interpretation of the word is considered an intended use and does not impart any further structural limitation of on the claimed subject matter.
Singh (2019) was cited for further teaching that 5-9 small organoids were implanted per graft [column 14 ¶ 2]. As discussed above, Singh (2019) teaches that the large-eye cat model is relevant to human therapies [column 14 ¶ 2]; as such, the surgical device of Singh (2019) is either itself suitable for implantation of retinal tissue units into a human eye, or it would have been obvious from the teachings of Singh (2019) to use a corresponding surgical device suitable for implantation into a human eye. Therefore, Singh (2019) teaches a collection of reagents which comprises 5-9 organoids/ retinal tissue units as described above and a surgical implantation device capable of implanting said tissue units into a human eye. Additionally, as discussed above for claim 19, an ordinarily skilled artisan would be motivated to use the method of Singh (2019), and, as such, it would follow, that an ordinarily skilled artisan would likewise be motivated to use the collection of reagents/ kit taught by Singh (2019) (comprising 5-9 retinal tissue units/graft and a surgical implantation device capable of implanting said tissue units into a human eye) to carry-out the disclosed procedure.
Regarding argument 10), that the specific hollow architecture as presently claimed addresses previously unsolved problems in retinal tissue engineering, such that the specific structural features claimed represent a significant advance in retinal tissue engineering by addressing critical limitation of prior approaches, note that Applicant has not provided any evidence that the instant claims address previously unsolved problems in retinal tissue engineering, nor indicated in what respect the current structure addresses said unsolved problems. Additionally, the cited art meets the limitations of the structure as claimed, and Applicant has not indicated in what way the instant claims meet the unsolved problems to an extent not met by the cited references. Applicant has also not indicated how the instant claims address critical limitations of prior approaches, nor what those critical limitations are. Further, as discussed above, the instant disclosure teaches examples of retinal tissue units of the instant invention, but does not provide any data indicating any kind of superior function of the instant retinal tissue units. Therefore, given that the cited references meet the claim limitations as written, either the claims are not commensurate in scope with the significant advance in retinal tissue engineering or the instant retinal tissue units do not represent such a significant advance.
Accordingly, neither Applicant’s amendments nor arguments overcome a finding of obviousness under 35 USC 103 over Singh (2015), Feyeux, Sing (2018), Rizzolo, and Singh (2019), and the rejection is maintained.
Double Patenting
The provisional rejection of amended, original, and cancelled claims 1-21 on the ground of nonstatutory double patenting as being unpatentable over claims 1-24 of copending Application No. 18/270,931, hereafter referred to as the ‘931 application, in view of Singh et al. (2015, Stem Cell & Development, 24(23), 2778-2795), is withdrawn over cancelled claim 21 and maintained over original and amended claims 1-20 in view of Applicant’s cancellation of claim 21. Applicant's amendments to the claims and arguments have been fully considered but have not been found persuasive in overcoming the rejection for reasons of record as discussed in detail below.
Applicant amended the claims to address issues of indefiniteness, but has not narrowed the scope of the claims to make the claims subject to the rejection patentably distinct from the reference claims.
Applicant argues that:
present claims are novel over Singh (2015) and also non-obvious over Singh (2015) even as combined with 4 other references; and
the earliest priority claimed in the co-pending application is after the priority date of the instant application, and since the present claims are novel and non-obvious, the double-patenting rejection must be withdrawn.
However, this is not agreed.
Regarding argument 1), as discussed above, Applicant’s amendments and arguments have not overcome a finding of anticipation under 35 USC 102(a)(1) by Singh (2015) nor a finding of obviousness under 35 USC 103 over Singh (2015) in view of Feyeux, Singh (2018), Rizzolo, and Singh (2019).
Regarding argument 2), the present claims are currently not allowable Provisional nonstatutory double patenting rejections do not require that the co-pending application have a prior effective filing date. As set forth in MPEP 804(I)(B)(1), if two (or more) pending applications are filed, in each of which a rejection of one claimed invention over the other on the ground of provisional nonstatutory double patenting (NSDP) is proper, the provisional NSDP rejection will be made in each application (emphasis added). Additionally, a complete response to a nonstatutory double patenting (NDP) rejection is either a reply by applicant showing that the claims subject to the rejection are patentably distinct from the reference claims or the filing of a terminal disclaimer in accordance with 37 CFR 1.321 in the pending application(s) with a reply to the Office action (MPEP 804 (B)(1)). Such a response is required even when the nonstatutory double patenting rejection is provisional.
Therefore, Applicant’s amendments and arguments do not overcome the provisional nonstatutory double rejection over claims 1-24 of copending Application No. 18/270,931, in view of Singh et al. (2015, Stem Cell & Development, 24(23), 2778-2795), and the rejection is maintained.
Conclusion
No claim is allowed.
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.
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DR. KATIE L. PENNINGTON
Examiner
Art Unit 1634
/KATIE L PENNINGTON/Examiner, Art Unit 1634
Dr. A.M.S. Wehbé
/ANNE MARIE S WEHBE/Primary Examiner, Art Unit 1634