DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
The Examiner for this Application has changed. Please direct all future correspondence to Katie Pennington, AU 1634. Additional contact information can be found at the end of this paper.
Applicant’s Response to Election/Restriction Filed, Amendment, and Arguments/Remarks, filed 19 May 2025, have been entered. Claims 1-27 were previously pending in the application. Applicant canceled claims 1, 17, and 23. Claims 2-16, 18-22, and 24-27 are currently pending. Claims 24, 25, and 26 are independent claims.
Claims 2, 4, 6, 7, 8, 11, 14, 16, 18-22, 24, 25, and 26 are amended by Applicants’ amendment filed on 19 May 2025. Claims 2, 7, 14 and 18-22 have been amended to correct their dependency on claim 25. Applicant’s election without traverse of the invention of Group IV, drawn to a method of producing a neural retina sheet, is acknowledged.
Additionally, applicant’s election of the following species:
Single tissue marker: A) brain: a. telencephalon,
in a reply filed 19 May 2025 is acknowledged. While Applicant has not indicated whether this election of species has been made with or without traverse, Applicant has not provided any arguments traversing the election of species requirement(s). Therefore, the election of species telencephalon is considered to have been made without traverse. Upon further consideration, Examiner has withdrawn the election of species requirement for a single tissue marker.
Claim 24 of restricted Group III is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim.
Claims 2-16, 18-22, and 25-27 are currently pending in the application and under examination to which the following grounds of rejection are applicable. An action on the merits follows.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/JP2020/011254, filed 13 March 2020, which claims priority to Japan 2019-046505, filed 13 March 2019. Filing of a certified copy of the Japan 2019-046505, filed 13 March 2019 is acknowledged.
Thus, the earliest possible priority for the instant application is 13 March 2019.
Information Disclosure Statement
The information disclosure statements filed 08 September 2021, 07 October 2021, 14 December 2022, 01 February 2023, 14 March 2023, 09 October 2023, and 22 May 2024 have been considered by the Examiner.
Specification
The disclosure is objected to because of the following informalities: the Brief Description of the Drawings does not include a description of each panel. Specifically, Figures 8,-9, and 14 do not include individual descriptions of panels A and B. See MPEP 608.01(f), which states, “When there are drawings, there shall be a brief description of the several views of the drawings and the detailed description of the invention shall refer to the different views by specifying the numbers of the figures, and to the different parts by use of reference letters or numerals”. Further, MPEP 608.01(f) instructs Examiners such that “If the drawings show Figures 1A, 1B, and 1C and the brief description of the refers only to Figure 1, the examiner should object to the brief description, and require applicant to provide a brief description of Figures 1A, 1B, and 1C.” Appropriate correction is required.
The use of the term “Essential 8” in [0055], “S-medium” in [0055], “StemPro” in [0055], “hESF9” in [0055], “mTeSR1” in [0055], “mTeSR2” in [0055], “TeSR-E8” in [0055], “StemFit” in [0055, 0181-0183], “iPS 2.0 Sendai Reprogramming Kit” in [0181], “IMDM” in [185], “TrypLE Select” in [0185], “DMEM/F12” in [0196-0197] “RNeasy” in [0199], “Human Genome U133 Plus2.0” in [0199], “Nanodrop” in [0225], “96.96 Dynamic Array IFC” in [0225], “IFC Controller HS” in [0225], “Biomark HD” in [0229, 0253], “CytoFix” in [0263], which are trade names and/or marks used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term. Note that the specification has not been inspected with sufficient detail to ensure identification of all uses of trade names and/or marks used in commerce. It is Applicant’s responsibility to ensure complete compliance.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 3 and 5 are objected to because of the following informalities: claim 3 recites lists of gene abbreviations without first writing out the terms which the abbreviations represent. Appropriate correction is required.
Claim 16 is objected to because of the following informalities: claim 16 recites “comprising the following steps (1) to (4) (5)”, which appears to be a typographical error in which the (4) was not deleted when the (5) was inserted. Appropriate correction is required.
Claim 25 is objected to because of the following informalities. Where a claim sets forth a plurality of elements or steps, each element or step of the claim should be separated by a line indentation, 37 CFR 1.75(i). In the instant case, subparts (4) and (5) should be further indented and subparts (6)-(10) should be replaced for “wherein” clauses. Appropriate correction is requested.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2-16, 18-22, and 25-27 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Independent claim 25 has multiple issues of indefiniteness.
Independent claim 25 recites, “the surface of the neural retinal layer having an apical surface” in line 11. Firstly, there is insufficient antecedent basis for “the surface of the neural retinal layer” limitation in the claim. Although surfaces are inherent to layers, any layer of cells will inherently have multiple surfaces, and as such, it is unclear which surface the limitation “the surface” is referring to. Secondly, “the surface of the neural retinal layer having an apical surface” is indefinite because it is unclear whether the surface has an apical surface or the neural retinal layer has an apical surface. If the surface has the apical surface, then it is unclear how a surface can have an apical surface. If the neural retinal has the apical surface, then it is unclear what is meant to be encompass merely by stating the surface of a thing (e.g., the neural retinal layer having an apical surface) without additional limitation or attributes of the recited surface. As such, the metes and bounds of the claim cannot be determined.
Independent claim 25 recites, “the inner layer being present inside the photoreceptor layer” in line 12. The term “inside” in claim 25 is a relative term which renders the claim indefinite. The term “inside” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear how one layer can be inside another layer or in what way one layer is inside another layer. For example, it is unclear whether the inside layer must be completely encompassed within the outside layer without making the outside layer be separate layers, whether the layers are merely overlapping in at least one dimension of space, or whether the inside layer is adjacent to the outside layer, wherein the “inside” and “outside” refer to some coordinate not defined by the relationship between the two layers themselves. As such, the metes and bounds of the claim cannot be determined.
Independent claim 25 recites, “the inner layer being present inside the photoreceptor layer present along the apical surface” in line 12. Firstly, there is insufficient antecedent basis for “the photoreceptor layer present along the apical surface” limitation in the claim. Independent claim 1 has a prior recitation of “a photoreceptor layer” in line 6 and “the photoreceptor layer” in line 7, but has no prior recitation of any photoreceptor layer present along the apical surface. Additionally, it is further unclear whether recitation of “the photoreceptor layer present along the apical surface” is meant to distinguish it from any prior recited photoreceptor layer(s) which are not present along the apical surface or whether it is meant to further limit the photoreceptor layer such that the photoreceptor layer is only present at the apical surface. As such, the metes and bounds of the claim cannot be determined.
Independent claim 25 recites, “the surface of the neural retina sheet” in lines 14-15. There is insufficient antecedent basis for “the surface of the neural retina sheet” limitation in the claim. Although surfaces are inherent to sheets, any sheet of cells will inherently have multiple surfaces, and as such, it is unclear which surface the limitation “the surface” is referring to. As such, the metes and bounds of the claim cannot be determined.
Claim 25 is indefinite in its recitation of “the expression of neural retina-related cell-related gene” and “ the expression of non-neural retina-related cell-related gene” in lines 18-19, there is not proper antecedent bases in the claim for any retina-related cell-related gene and non-neural retina-related cell-related gene and their expression. As such the metes and bounds of the claim are indefinite.
Claim 25 is indefinite in its recitation of “derived” in lines 2 and 24. The metes and bounds of this term are indefinite because “derived” can encompass multiple meanings from the origin of something to deducing something. Therefore, the intended mean of the term, “derived” is vague and indefinite. For the purpose of a compact prosecution the term “derived” recited in claim 25 has been interpreted as “obtained from”.
Claim 25 recites, “a cell aggregate containing a neural retina having an epithelial structure derived from a pluripotent stem cell” in lines 24-25, which is indefinite because 1) it is unclear whether the neural retina itself is required to have an epithelial structure or whether the cell aggregate more broadly is required to have an epithelial structure; and 2) it is unclear whether the claim requires the full cell aggregate to be derived from a pluripotent stem cell, the neural retina to be derived from a pluripotent stem cell, or if only the epithelial structure is required to be derived from a pluripotent stem cell. As such, the metes and bounds of the claim cannot be determined.
Independent claim 25 recites, “neural retina (transplant neural retina)” in lines 32, 34, and 36, which is indefinite because it is unclear whether the phrase in parentheses is further limiting the term “neural retina” or is merely illustrative of an example of a neural retina or an alternative name for the neural retina. It is not clear whether the parenthetical is used to indicate a limitation, a preferred embodiment, or synonym, etc. As such, the metes and bounds of the claim cannot be determined.
Independent claim 25 recites, “the cell aggregate containing the sample for quality determination being the part” in lines 32-33 and 34-35, which has multiple issues of indefiniteness. Firstly, there is insufficient antecedent basis for this limitation in the claim. Claim 25 recites “a cell aggregate containing a neural retina having an epithelial structure” in lines 24-25 and “the cell aggregate” in line 26, but has no prior recitation of a cell aggregate containing the sample for quality determination. Claim 25 recites “sampling a part or the whole of the cell aggregate as a sample for quality determination” in lines 26-27 and “detecting the expression” of genes within the sample [in lines 28-29] to determine if the sample is applicable as the transplant neural retina. Therefore, to the extent that “the cell aggregate containing the sample for quality determination” refers to the cell aggregate from which the sample for quality determination was sampled, it is further unclear how the sample for quality determination has been “sampled” from the cell aggregate, used for gene expression analysis, and is still comprised within the cell aggregate such that the cell aggregate contains the sample for quality determination following the gene expression analysis. As such, the metes and bounds of the claim cannot be determined.
Independent claim 25 recites, “the cell aggregate of the sample for quality determination being the whole”, which has multiple issues of indefiniteness. Firstly, there is insufficient antecedent basis for this limitation in the claim. Claim 25 recites “a cell aggregate containing a neural retina having an epithelial structure” in lines 24-25, “the cell aggregate” in line 26, “the same cell aggregate as the cell aggregate containing the sample for quality determination being the part” in lines 32-33, and “a cell aggregate of the same lot as that of the cell aggregate containing the sample for quality determination being the part” in lines 34-35, but has no prior recitation of a cell aggregate of the sample for quality determination. Additionally, “cell aggregate of the sample for quality determination” is further indefinite because it is unclear in what way the cell aggregate is “of” the sample. As such, the metes and bounds of the claim cannot be determined.
Independent claim 25 recites, “the same lot” in lines 34 and 36. There is insufficient antecedent basis for this limitation in the claim. Claim 25 has no prior recitation of any lot. As such, the metes and bounds of the claim cannot be determined.
Claim 25 is indefinite for the recitation of both a product (a neuronal retina sheet) and the method steps of producing a product (a neuronal retina sheet) in a single claim (See; MPEP 2173.05(p); and IPXL Holdings v. Amazon.com, Inc., 430 F.2d 1377, 1384, 77 USPQ2d 1140, 1145 (Fed. Cir. 2005); Ex parte Lyell, 17 USPQ2d 1548 (Bd. Pat. App. & Inter. 1990) (claim directed to an automatic transmission work stand and the method of using it held ambiguous and properly rejected under 35 U.S.C. 112, second paragraph).
Claims 2-16, 18-22, and 27 are included in this rejection due to their dependence on claim 25.
Claim 2 recites, “the brain and spinal cord tissue marker gene is one or more genes selected from the group consisting of telencephalon marker gene, diencephalon/midbrain marker gene, and spinal cord marker gene” in lines 2-4, which is indefinite because the telencephalon, diencephalon/midbrain, and spinal cord are either brain OR spinal cord tissues, and therefore marker genes for these regions specifically are not “brain and spinal cord tissue marker genes”. As such, the metes and bounds of the claim cannot be determined.
Claim 6 has multiple issues of indefiniteness.
Claim 6 recites, “the cell aggregate” in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 6 is dependent on independent claim 25. Claim 25 recites, “a cell aggregate containing a neural retina” in line 24, “the same cell aggregate as the cell aggregate containing the sample for quality determination being a part” in lines 32-33, “a cell aggregate of the same lot as that of the cell aggregate containing the sample of quality determination being a part” in lines 34-35, and “a cell aggregate of the same lot as that of the cell aggregate of the sample for quality determination being the whole” in lines 36-37. Therefore, it is unclear which cell aggregate “the cell aggregate” of claim 6 line 1 is referring to. As such, the metes and bounds of the claim cannot be determined.
Claim 6 also recites, “the sample for quality evaluation” in line 2. There is insufficient antecedent basis for this limitation in the claim. Neither claim 6 nor claim 25 have any prior recitation of a sample for quality evaluation. As such, the metes and bounds of the claim cannot be determined.
Claim 6 also recites, “the transplant neural retina” in line 3. There is insufficient antecedent basis for this limitation in the claim. Claim 6 is dependent on claim 25. Claim 25 recites “a transplant neural retina” in line 23 and “the neural retina (transplant neural retina)” in lines 32, 34, and 36. Therefore, it is unclear to which transplant neural retina “the transplant neural retina” of claim 6 line 3 is referring. As such, the metes and bounds of the claim cannot be determined.
Claim 6 recites, “the cell aggregate of the sample for quality evaluation” in lines 1-2, which is indefinite because it is unclear how the cell aggregate is “of “ the sample for quality evaluation”. As such, the metes and bounds of the claim cannot be determined.
Claim 6 recites, “a cell aggregate produced under a condition exhibiting a gene expression profile equivalent to that of the transplant neural retina” in lines 2-3, which has multiple issues of indefiniteness. Firstly, it is unclear how a condition can exhibit a gene expression profile. Secondly, it is unclear what is encompassed by the term “equivalent” for the gene expression profile to be equivalent to that of the transplant neural retina. As such, the metes and bounds of the claim cannot be determined.
Claim 7 has multiple issues of indefiniteness.
Claim 7 recites, “the cell aggregate” in lines 2 and 5. There is insufficient antecedent basis for this limitation in the claim. Claim 7 is dependent on independent claim 25. Claim 25 recites, “a cell aggregate containing a neural retina” in line 24, “the same cell aggregate as the cell aggregate containing the sample for quality determination being a part” in lines 32-33, “a cell aggregate of the same lot as that of the cell aggregate containing the sample of quality determination being a part” in lines 34-35, and “a cell aggregate of the same lot as that of the cell aggregate of the sample for quality determination being the whole” in lines 36-37. Therefore, it is unclear which cell aggregate “the cell aggregate” of claim 7 lines 2 and 5 are referring to. As such, the metes and bounds of the claim cannot be determined.
Claim 7 recites, “it is determined that a neural retina continuous or adjacent at least partially to the part in the same cell aggregate as the cell aggregate containing the sample for quality determination being the part” in lines 4-6, which is indefinite because it is unclear how the cell aggregate can contain the sample for quality determination in that the sample for quality determination is a sample of the cell aggregate which was used for gene expression determination, and thus has been removed from the aggregate.
Claim 7 recites, “the transplant neural retina” in lines 6-7. There is insufficient antecedent basis for this limitation in the claim. Claim 7 is dependent on claim 25. Claim 25 recites “a transplant neural retina” in line 23 and “the neural retina (transplant neural retina)” in lines 32, 34, and 36. Therefore, it is unclear to which transplant neural retina “the transplant neural retina” of claim 7 lines 6-7 is referring. As such, the metes and bounds of the claim cannot be determined.
Claim 8 has multiple issues of indefiniteness.
Claim 8 recites, “the transplant neural retina” in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 8 is dependent on claim 7, which is dependent on claim 25. Claim 7 recites, “the transplant neural retina” in lines 6-7. Claim 25 recites “a transplant neural retina” in line 23 and “the neural retina (transplant neural retina)” in lines 32, 34, and 36. Therefore, it is unclear to which transplant neural retina “the transplant neural retina” of claim 8 line 1 is referring. As such, the metes and bounds of the claim cannot be determined.
Claim 8 also recites, “is contained in the same epithelial tissue as that of the sample for quality determination” in line 2. There is insufficient antecedent basis for this limitation in the claim. None of 25, 7, nor 8 have any prior recitations of an epithelial tissue. As such, the metes and bounds of the claim cannot be determined.
Claim 9 has multiple issues of indefiniteness.
Claim 9 recites, “the transplant neural retina” in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 9 is dependent on claim 8. Claim 8 is dependent on claim 7, which is dependent on claim 25. Claim 8 recites, “the transplant neural retina” in line 1. Claim 7 recites, “the transplant neural retina” in lines 6-7. Claim 25 recites “a transplant neural retina” in line 23 and “the neural retina (transplant neural retina)” in lines 32, 34, and 36. Therefore, it is unclear to which transplant neural retina “the transplant neural retina” of claim 9 line 1 is referring. As such, the metes and bounds of the claim cannot be determined.
Claim 9 also recites, “the transplant neural retina contains the center and/or its neighborhood of the same epithelial tissue” in lines 1-2, which has multiple issues of indefiniteness. Firstly, note that claim 9 is dependent on claim 8; it is unclear how the transplant neural retina in contained in the same epithelial tissue (as recited in claim 8) and also contains the center and/or its neighborhood of the same epithelial tissue. Secondly, recitation of, “the center and/or its neighborhood of the same epithelial tissue”, which is indefinite because it is unclear what is encompassed by “the center” or “its neighborhood”. Regarding “the center”, it is unclear which dimension(s) “the center” is referring to, such as the vertical center and/or center of length and/or center of depth. Regarding “its neighborhood”, it is firstly unclear whether “its” refers to the transplant neural retina or to the center, and secondly unclear what/ how much of a region of an epithelial tissue is encompassed as a “neighborhood”. As such, the metes and bounds of the claim cannot be determined.
Claim 10 has multiple issues of indefiniteness.
Claim 10 recites, “the transplant neural retina” in line 1. There is insufficient antecedent basis for this limitation in the claim. Claim 10 is dependent on claim 9, which dependent on claim 8. Claim 8 is dependent on claim 7, which is dependent on claim 25. Claim 9 recites, “the transplant neural retina” in line 1. Claim 8 recites, “the transplant neural retina” in line 1. Claim 7 recites, “the transplant neural retina” in lines 6-7. Claim 25 recites “a transplant neural retina” in line 23 and “the neural retina (transplant neural retina)” in lines 32, 34, and 36. Therefore, it is unclear to which transplant neural retina “the transplant neural retina” of claim 10 line 1 is referring. As such, the metes and bounds of the claim cannot be determined.
Claim 10 also recites, “wherein the transplant neural retina is continuous epithelial tissue”, which his indefinite because it is unclear how a neural retina, which is neural tissue, can be continuous epithelial tissue. As such, the metes and bounds of the claim cannot be determined.
Claim 11 has multiple issues of indefiniteness.
Claim 11 recites, “the cell aggregate containing a neural retina contains first epithelial tissue containing the transplant neural retina”, which is indefinite because it is unclear how a first epithelial tissue “contains” a neural tissue. For example, it is unclear whether the neural retina is required to be completely surrounded by the epithelial tissue or whether the neural retina merely needs to be in contact with, adjacent to, or near the epithelial tissue. As such, the metes and bounds of the claim cannot be determined.
Claim 11 recites, “the transplant neural retina” in lines 2-3, 6, and 9. There is insufficient antecedent basis for this limitation in the claim. Claim 11 is dependent on claim 7, which is dependent on claim 25. Claim 7 recites, “the transplant neural retina” in lines 6-7. Claim 25 recites “a transplant neural retina” in line 23 and “the neural retina (transplant neural retina)” in lines 32, 34, and 36. Therefore, it is unclear to which transplant neural retina “the transplant neural retina” of claim 11 lines 2-3, 6, and 9 are referring. As such, the metes and bounds of the claim cannot be determined.
Claim 11 recites, “the surface of the first epithelial tissue” in lines 4-5. There is insufficient antecedent basis for this limitation in the claim. Claim 11 recites a first epithelial tissue, but has no prior recitation of any particular surface of the first epithelial tissue. Given that a tissue has multiple surfaces, it is unclear which surface “the surface” is referring to. As such, the metes and bounds of the claim cannot be determined.
Claim 15 has multiple issues of indefiniteness.
Claim 15 recites, “the transplant neural retina” in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 15 is dependent on claim 14, which is dependent on claim 25. Claim 25 recites “a transplant neural retina” in line 23 and “the neural retina (transplant neural retina)” in lines 32, 34, and 36. Therefore, it is unclear to which transplant neural retina “the transplant neural retina” of claim 11 lines 2-3, 6, and 9 are referring. As such, the metes and bounds of the claim cannot be determined.
Claim 15 recites, “comprising as being applicable as the transplant neural retina when the following reference 1 and reference 2 are satisfied:
reference 1: the difference between eh threshold cycle (Ct) value of the neural retina-related cell-related gene and the Ct value of an internal standard gene (ΔCt value) is 10 or less, and
reference 2: the difference between the Ct value of the non-neural retina-related cell-related gene and the Ct value of the internal standard gene (ΔCt value) is 5 or more”.
However, claim 25 recites “when the expression of the neural retina-related cell-related gene is found and the expression of the non-neural retina-related cell-related gene is not found, determining that … the neural retina… is applicable as the transplant neural retina”. Therefore, claim 25 requires that the neural retina-related cell-related gene be “found” in the sample for quality determination and the non-neural retina-related cell-related gene be “not found” in the sample. However, the limitation of claim 15 not only allows for the non-neural retina-related cell-related gene to be present in the sample, but allows for the non-neural retina-related cell-related gene to be present at a higher level than the neural retina-related cell-related gene (e.g., when the internal standard gene is more abundant than either the neural retina-related cell-related gene and the non-neural retina-related cell-related gene, when the difference is calculated by subtracting the standard gene Ct from the neural or non-neural gene Ct, and wherein the ΔCt for the non-neural retina-related cell-related gene is lower than the ΔCt for the neural retina-related cell-related gene, such as for the non-neural retina gene to have a ΔCt of 10 and the neural retina gene to have a ΔCt of 10). Note that as written, the “difference between” does not specify which term is the greater term, and the ΔCt values of 10 or less encompass all negative values for ΔCt obtained when the larger Ct value is subtracted from the smaller Ct value.
Claim 16 has multiple issues of indefiniteness.
Claim 16 recites, “8 or more and 800 or less” in lines 5-6 and 6-7, which is indefinite because it is unclear whether Applicant intends the claim to encompass at least 8 to no more than 800 or whether Applicant intends to encompass both 8 or more groups in addition to 800 or less groups. As such, the metes and bounds of the claim cannot be determined.
Claim 16 recites, “solutions containing nucleic acids obtained from the two or more of the samples for quality determination (sample solutions)” in lines 8-10 and “a solution containing one or a plurality of primers specific for each of one or more of the neural-retina-related cell-related genes or the non-neural retina-related cell-related genes (primer solution)” in lines 10-12, which are indefinite because is it unclear whether the terms in parentheses are further limiting the preceding terms, are merely exemplary of the preceding terms, or are merely renaming the preceding terms. As such, the metes and bounds of the claim cannot be determined.
Claim 16 recites, “so as to be different primer well groups” in line 16. The term “different” in claim 16 is a relative term which renders the claim indefinite. The term “different” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear in what way adding the primer solution to one or more primer wells in the one or more primer well groups leads to them being different primer well groups, such as in what way they are “different” and in respect to what reference they are “different”. As such, the metes and bounds of the claim cannot be determined.
Claim 18 recites, “the major axis” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Claim 18 is dependent on claim 25. Neither claim 18 nor claim 25 have any prior recitation of any major axis. Additionally, claim 18 does not recite what the major axis is an axis of. As such, it is unclear which major axis “the major axis” is referring to. Therefore, the metes and bounds of the claim cannot be determined.
Claim 19 recites, “the minor axis” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Claim 19 is dependent on claim 25. Neither claim 19 nor claim 25 have any prior recitation of any minor axis. Additionally, claim 19 does not recite what the minor axis is an axis of. As such, it is unclear which minor axis “the minor axis” is referring to. Therefore, the metes and bounds of the claim cannot be determined.
Claim 20 has multiple issues of indefiniteness.
Claim 20 recites, “the height” in lines 1-2. There is insufficient antecedent basis for this limitation in the claim. Claim 20 is dependent on claim 25. Neither claim 20 nor claim 25 have any prior recitation of any height. Additionally, claim 20 does not recite what the height is the height of. As such, it is unclear which height “the height” is referring to. Therefore, the metes and bounds of the claim cannot be determined.
Claim 20 recites, “contains a region of the center and/or its neighborhood of continuous epithelial tissue” in line 4, which is indefinite because it is unclear what is encompassed by “the center” or “its neighborhood”. Regarding “the center”, it is unclear which dimension(s) “the center” is referring to, such as the vertical center and/or center of length and/or center of depth. Regarding “its neighborhood”, it is firstly unclear whether “its” refers to the neural retina sheet or to the center, and secondly unclear what/ how much of a region of a neural retinal sheer or continuous epithelial tissue is encompassed as a “neighborhood”. As such, the metes and bounds of the claim cannot be determined.
Claim 22 has multiple issues of indefiniteness.
Claim 22 recites, “the cell aggregate” in line 5. There is insufficient antecedent basis for this limitation in the claim. Claim 22 is dependent on independent claim 25. Claim 22 has a prior recitation of “a cell aggregate” in line 3. Claim 25 also recites, “a cell aggregate containing a neural retina” in line 24, “the same cell aggregate as the cell aggregate containing the sample for quality determination being a part” in lines 32-33, “a cell aggregate of the same lot as that of the cell aggregate containing the sample of quality determination being a part” in lines 34-35, and “a cell aggregate of the same lot as that of the cell aggregate of the sample for quality determination being the whole” in lines 36-37. Therefore, it is unclear which cell aggregate “the cell aggregate” of claim 22 line 5 is referring to. As such, the metes and bounds of the claim cannot be determined.
Claim 22 recites, “the surface of the first epithelial tissue” in line 7. There is insufficient antecedent basis for this limitation in the claim. Claim 22 recites a first epithelial tissue, but has no prior recitation of any particular surface of the first epithelial tissue. Given that a tissue has multiple surfaces, it is unclear which surface “the surface” is referring to. As such, the metes and bounds of the claim cannot be determined.
Independent claim 26 has multiple issues of indefiniteness.
Firstly, claim 26 recites “sampling a sample for quality evaluation from each of 2 or more and 800 or less cell aggregates”, which is indefinite because it is unclear whether the claim requires sampling from 2 or more cell aggregates and additionally sampling from 800 or less cell aggregates or whether the sampling is from at least 2 to not more than 800 cell aggregates. As such, the metes and bounds of the claim cannot be determined.
Secondly, claim 26 recites, “the sample for quality evaluation” in line 4. There is insufficient antecedent basis for this limitation in the claim. Claim 26 line 2 recites, “sampling a sample for quality evaluation from each of 2 or more and 800 or less cell aggregates”, as such, it is unclear which of the 2 or more and 800 or less samples for quality evaluation “the sample for quality evaluation” is referring to. As such, the metes and bounds of the claim cannot be determined.
Claim 26 recites, “the cell aggregate” in line 4. There is insufficient antecedent basis for this limitation in the claim. Claim 26 line 2 recites, “2 or more and 800 or less cell aggregates”, as such, it is unclear which of the 2 or more and 800 or less cell aggregates “the cell aggregate” is referring to. Therefore, the metes and bounds of the claim cannot be determined.
Claim 26 recites, “cell aggregates containing a neural retina having an epithelial structure derived from a pluripotent stem cell” in lines 2-4, which is indefinite because it is unclear whether the claim requires the cell aggregates to be derived from a pluripotent stem cell, the neural retina to be derived from a pluripotent stem cell, or if only the epithelial structure is required to be derived from a pluripotent stem cell. As such, the metes and bounds of the claim cannot be determined.
Additionally, claim 26 recites, “the sample for quality determination” in lines 6 and 9. There is insufficient antecedent basis for this limitation in the claim. Claim 26 recites “a sample for quality evaluation” in line 2 and “the sample for quality evaluation” in line 4, but has no prior recitation of a sample for quality determination. As such, the metes and bounds of the claim cannot be determined.
Independent claim 26 recites, “the neural retina in the same cell aggregate as the cell aggregate containing the sample for quality determination being the part” in lines 9-10, which has multiple issues of indefiniteness. Firstly, there is insufficient antecedent basis for this limitation in the claim. Claim 26 recites “sampling a sample for quality evaluation from each of 2 or more and 800 or less cell aggregates” in lines 2-3. Therefore, it is unclear which cell aggregate “the cell aggregate” in line 9 is referring to, and to the extent that “the sample for quality determination” is referring to “a sample for quality evaluation” of line 2, it is unclear which of the samples for quality evaluation “the sample for quality determination” is referring to. Additionally, claim 26 recites “sampling a sample for quality evaluation from each of 2 or more and 800 or less cell aggregates” in lines 2-3, “detecting the expression” of genes “in the cell sample for quality determination” [lines 5-6], and then determining based on the detecting that the neural retinal is applicable as the transplant neural retina. Therefore, it is unclear how the cell aggregate can contain the sample for quality determination following the sampling and detection of genes within the sample. As such, the metes and bounds of the claim cannot be determined.
Claim 26 is indefinite in its recitation of “the expression of neural retina-related cell-related gene” and “ the expression of non-neural retina-related cell-related gene” in lines 5-6, there is not proper antecedent bases in the claim for any retina-related cell-related gene and non-neural retina-related cell-related gene and their expression. As such the metes and bounds of the claim are indefinite.
Claim 26 is indefinite in its recitation of “derived”. Without a clear statement of the process by which the starting material is derivatized, it is not possible to know the metes and bounds of a "derivative" because any given starting material can have many divergent derivatives depending on the process of derivatization, especially since the claimed starting material encompasses a pluripotent stem cell that can differentiated into multiple structures .
For the purpose of a compact prosecution the term “derived” recited in claim 26 has been interpreted as “obtained from”.
Independent claim 26 recites, “the transplant neural retina” in line 10. There is insufficient antecedent basis for this limitation in the claim. Claim 26 has no prior recitation of a transplant neural retina. As such, the metes and bounds of the claim cannot be determined.
Claim 27 has multiple issues of indefiniteness.
Claim 27 recites, “the cell aggregate” in line 2. There is insufficient antecedent basis for this limitation in the claim. Claim 27 is dependent on independent claim 25. Claim 25 recites, “a cell aggregate containing a neural retina” in line 24, “the same cell aggregate as the cell aggregate containing the sample for quality determination being a part” in lines 32-33, “a cell aggregate of the same lot as that of the cell aggregate containing the sample of quality determination being a part” in lines 34-35, and “a cell aggregate of the same lot as that of the cell aggregate of the sample for quality determination being the whole” in lines 36-37. Therefore, it is unclear which cell aggregate “the cell aggregate” of claim 27 line 2 is referring to. As such, the metes and bounds of the claim cannot be determined.
Claim 27 recites, “the surface of the first epithelial tissue” in lines 5-6. There is insufficient antecedent basis for this limitation in the claim. Claim 27 recites a first epithelial tissue, but has no prior recitation of any particular surface of the first epithelial tissue. Given that a tissue has multiple surfaces, it is unclear which surface “the surface” is referring to. As such, the metes and bounds of the claim cannot be determined.
Claim 27 recites, “the transplant neural retina” in lines 7 and 7-8. There is insufficient antecedent basis for this limitation in the claim. Claim 27 is dependent on claim 25. Claim 25 recites “a transplant neural retina” in line 23 and “the neural retina (transplant neural retina)” in lines 32, 34, and 36. Therefore, it is unclear to which transplant neural retina “the transplant neural retina” of claim 27 lines 7 and 7-8 are referring. As such, the metes and bounds of the claim cannot be determined.
Claim 27 recites, “the transplant neural retina contains a region on the first epithelial tissue” in lines 7-8, which is indefinite because it is unclear how the transplant neural retina can contain a region on the first epithelial tissue. Specifically, claim 27 also recites, “wherein the first epithelial tissue contains a human neural retina” in lines 3-4, and so it is unclear how the first epithelial tissue can contain the neural retina while the neural retina itself contains a region on the first epithelial tissue. As such, the metes and bounds of the claim cannot be determined.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 2-16, 18-22, and 25-27 are rejected under 35 U.S.C. 103 as being unpatentable over Nasonkin [US20210155895A1, filed 4 April 2017 with priority to U.S. Provisional Application Nos. 62/318,210, filed 4 April 2016, 62/354,806, filed 26 June 2016, and 62/465,459, filed 1 May 2017]; in view of Singh et al. [2015, Stem Cells & Development, 24(23), 2778-2795]; Mandai et al. [2017, New England Journal of Medicine, 376, 1038-46]; Sanchez-Freire et al. [2012, Nature Protocols, 7(5), 829-838]; Karlen et al. [2007, BMC Bioinformatics, 8, 131, 1-16]; and Sabin & Jones [2008, Nonlinear Systems Biology and Design: Surface Design, 54-65, Acadia Conference 10.52842/conf.acadia.2008.054].
Regarding independent claim 25, Nasonkin discloses a method for producing a neural retinal sheet/tissue slice, wherein the neural retina sheet is (1) derived from a pluripotent stem cell [title, abstract, 0003, Figure 33]; (2) having a three-dimensional structure [0003]; (3) comprising a neural retinal layer having a plurality of layer structures including a photoreceptor layer and an inner layer [0011, 0039, 0121]; (4) the photoreceptor layer comprising one or more cells selected from the group consisting of a photoreceptor precursor cell and a photoreceptor cell [0011, 0039]; (5) the inner layer comprising one or more cells selected from the group consisting of a retinal precursor cell, a ganglion cell, an amacrine cell, and a bipolar cell [0012, 0066, 0077], (6) the surface of the neural retinal layer having an apical surface [0074, 0094, 0189, Figure 1]; (7) the inner layer being present inside the photoreceptor layer present along the apical surface [0011, 0122, 0187, Figure 1, 9, 10, 16]; (8) the area of the neural retinal layer being 50% or more with respect to the total area of the surface of the neural retinal sheet [Figure 10, 16, 33]; (9) the area of a continuous epithelium structure being 80% or more with respect to the total area of the apical surface of the neural retinal layer [Figure 1, 9, 15, 16, 26]; (10) the expression of a neural retina-related cell-related gene(s) being found [0014-0023, Figure 20, 33] and the expression of non-neural retina-related cell-related gene(s) being not found in the neural retina sheet, wherein the non-neural retina-related cell-related gene(s) comprise one or more genes selected from the group consisting of cerebrospinal tissue marker gene and eyeball-related tissue marker gene [0026-0027, 0141-0142, 302-303, claims 14-15].
Nasonkin also discloses selecting a transplant neural retina determined as being suitable for transplantation [0010, 0147, 0273] by determining the quality of a cell aggregate containing a neural retina having an epithelial structure (e.g., RPE layer), wherein the cell aggregate is derived from a pluripotent stem cell [0003, 0010-0011, 0145, 0187-0190], wherein the quality determination is performed by sampling a part or the whole of the cell aggregate and detecting the expression of neural retina-related genes and non-neural retina-related genes [0188, 0272-0273, 0276, 0278, 0281-0285, 0293, 0302-0303], such that the sampled neural retina demonstrates expression of neural retina-related genes (e.g., PAX6, EZRIN, CRX, BRN3B) [0285, 0293] and does not express non-neural retina-related genes (e.g., NANOG, OCT3, and markers of cerebrospinal tissues such as markers of astrocytes, or oligodendrocytes) [0302-0303]. Nasonkin also teaches isolating the selected transplant neural retina [0068. 0120].
Regarding the selection of a cell aggregate from the same lot as the cell aggregate which was sampled for gene expression, Nasonkin discloses the generation of hESC-derived in vitro retinal tissue/3D retinal organoids, wherein “colonies” (plural) were grown, eventually giving rise to “retinal organoids” (plural) which were maintained, thereby teaching the preparation of multiple organoids at a time (e.g., lots of organoids) [0183]. Nasonkin also teaches batches of retinal organoids produced in different wells of a 96 well plate [0253], and that the number of aggregates obtained varied between 2-3 and 15 or more per 35-mm plate [0185]. Nasonkin discloses that using the methods and composition they disclose, it is possible to generate hundreds of such organoids [0190].
Nasonkin teaches that the pluripotent cell-derived, three-dimensional in vitro retinal tissue they disclose is suitable for transplantation in cell-based therapies for retinal degeneration [0010]. Nasonkin also teaches that one or more slices of 3D retinal organoid is transplanted to the eye of the subject in a manner that permits them to graft or migrate to the intended tissue site and reconstitute or regenerate the functionally deficient area [0147]. Nasonkin further teaches that a slice cut from a retinal organoid along a diameter or a chord provides a flat, ribbon-like piece of tissue suitable for transplantation with superior abilities to engraft and restore optical function [0147].
Therefore, given the teachings of Nasonkin that the neural retina produced by their method is suitable for transplantation with superior abilities to engraft and restore optical function, the teachings of Nasonkin of assessing the suitability of the neural retina by testing the gene expression patterns of neural retina samples (including detecting the presence of neural retina-associated genes and the non-presence of non-neural retina-associated genes), and the teachings of Nasonkin that multiple neural retina organoids were produced by the method at a time, an ordinarily skilled artisan at the time of filing the instant application would have been motivated to use an organoid of the same lot/preparation as the neural retina tested for gene expression as a transplant neural retina suitable for transplantation to provide superior abilities to engraft and restore optical function.
Regarding claims 2-3, Nasonkin teaches wherein the brain and spinal cord tissue marker gene is one or more genes selected from astrocyte or oligodendrocyte marker genes [0303].
Additionally, Nasonkin also teaches to include the outer RPE layer in the neural retina sheet for transplantation, but to exclude the inner RPE layer [Figure 16]. Therefore, Nasonkin is teaching to select a transplant neural retina which expresses the neural retina-related cell-related gene and to exclude tissue which expresses non-neural retina-related cell-related genes (e.g., RPE marker genes). However, Nasonkin does not teach to only transplant tissue which does not express the non-neural retina-related cell-related genes. Note further that independent claim 25, upon which claims 2 and 3 depend, recites that the neural retina sheet produced comprises an area of a continuous epithelium structure which is 80% or more with respect to the total area of the apical surface of the neural retinal layer (lines 16-17), thereby requiring the presence of an epithelial tissue, such as RPE. Therefore, the selection of the neural retina as not expressing non-neural retina marker genes (such as RPE marker genes) does not exclude the inclusion of RPE cells in the neural retina sheet.
Nasonkin teaches that the neural retina cells express neural retina-related genes and do not express RPE-related marker genes, as shown in Figu