Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of Claims
Claims 1, 4-11, 13-20, and 22-24 are pending.
Priority
Claims 1, 4-11, 13-20, and 22-24 are a CON of PCT/CN 2022/107890 filed on July 26, 2022, which has priority to CHINA 202110894939.7 filed on August 5, 2021.
Election/Restriction
Applicant’s election of invention I, directed to several different types of RDM culture medium compositions for the purpose of culturing multiple cell types, in the reply filed on July 16, 2026, is acknowledged. The election was made with traverse.
Invention II: Claims 8-9, 15, and 24 are directed to a method for inducing retinal pigment epithelial cells.
Invention III: Claim 10 is directed to a kit comprising at least one substance selected from BMP signaling pathway inhibitor, Wnt pathway inhibitor, an inhibitor of TGF-β type I receptors ALK5, ALK4, and ALK7, a ROCK pathway inhibitor, a WNT signaling pathway activator, a VEGFR kinase inhibitor, a GSK signaling pathway inhibitor, and a vitamin.
Invention IV: Claim 11 is directed towards multiple RDM culture mediums for the purpose of culturing and inducing several types of cells.
Applicant’s election with traverse of Invention I to include claims 1, 4-9, 13-14, 18-20, and 22-24 in the reply filed on July 13, 2026, is acknowledged. In considering Applicant’s amendments to the previously non-elected claims incorporating and/or requiring limitations of the elected Invention I, examiner has determined that examining claims directed to Inventions II-IV no longer presents a serious additional search and/or examination burden. Accordingly, the restriction requirement is withdrawn, and the claims previously associated with Inventions II-IV are reinstated and are being considered. Therefore, claims 1, 4-11, 13-20, and 22-24 are pending.
Drawings
The drawings are objected to because:
Figure 6 states “IHX2” list on the x-axis. It should be corrected to read “LHX2”.
. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
Paragraphs [00186] and [00210] should be corrected where the specification states “expression levels of PAX6, RPE65, IHX2…”. “IHX2” should read as “LHX2”.
Appropriate correction is required.
Claim Objections
Claims 4 and 7 are objected to for the following reasons:
Claim 4 recites “…the expression levels of PAX6, RPE65, IHX2, and pmel17…” should read “…the expression levels of PAX6, RPE65, [[I]]LHX2, and pmel17…”.
Claim 7 recites “comprising…glutamine and vitamin” should read “comprising…glutamine and a vitamin”.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
The claimed invention is directed to non-statutory subject matter. The claim(s) does/do not fall within at least one of the four categories of patent eligible subject matter because:
Claims 11, 13-17, and 18-20 are directed to nonstatutory subject matter where the claims recite “Application of” the culture medium and “Application of” the cells prepared. These claims are claiming a “use” per se without reciting a process comprising an act or series of acts.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 4-11, 14-20, and 22-24 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 recites “a RDM1 culture medium”. The “RDM” is not preceded with what “RDM” stands for, and the specification does not provide a definition of the meaning of “RDM”. Because of this, a person of ordinary skill in the art would not be able to reasonably ascertain what the meaning of “a RDM1 culture medium”. Additionally, claims 4 and 6-9 also recite an iteration of “RDM” and are also rejected as being indefinite under § 112(b).
Regarding claim 1, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 4, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 6, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 7, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 8, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 9, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Regarding claim 10, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 11 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 13 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 14 is 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.
Regarding claim 14, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 15 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 16 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 17 is 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.
Regarding claim 18, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 18 is 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.
Regarding claim 19, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 19 is 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.
Regarding claim 20, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
Claim 20 is 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.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 22 recites the broad recitation “at least 5%”, and the claim also recites “preferably at least 10%” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
A broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). In the present instance, claim 23 recites the broad recitation “at least 10%”, and the claim also recites “at least 20%” which is the narrower statement of the range/limitation. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims.
Claim 24 recites “wherein the expression levels of TYRP2, PEDF, PMEL17, RPE65, and CRALBP in the cell population are increased by at least 100 times relative to iPSCs”. However, the claim does not provide an objective standard for determining the recited 100-fold increase, e.g. is the claim referring to mRNA expression, protein expression, or another measure of expression. Additionally, the specification indicates that the iPSCs may be commercially available cell lines or may be induced from a donor. However, different iPSC populations may exhibit different baseline expression levels of the recited markers, the calculated fold increase may depend upon the particular iPSC population selected as the reference. Based on this, it is unclear what or how the given iPSC cell population would satisfy the “increased by at least 100 times relative to iPSCs”.
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 following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 1 and 4-5 are rejected under 35 U.S.C. §102(a)(1) as being anticipated by Ando and Kuroda (Hereinafter Ando) [US 2018 258388 A1].
Examiner’s note: The limitations introduced by the term “preferably” are considered nonlimiting and will not be expressly recited in the rejection. However, citations to the prior art disclosing such preferred embodiments will be provided where appropriate for in order to further compact prosecution.
Regarding claim 1, Ando teaches “a culture medium comprising (1) a RDM1 culture medium, comprising at least one of a BMP signaling pathway inhibitor [Fig. 7], a Wnt pathway inhibitor [Para starting with “In the method of the present invention, the Wnt signal transduction pathway inhibitor is not particularly limited”], an inhibitor of TGF-β type I receptors ALK5, ALK4 and ALK7 [Para starting with “[9] The production method according to any of the above-mentioned [1] to [8]”], and a ROCK pathway inhibitor [Para starting with “The medium to be used in the present invention optionally contains…a ROCK…inhibitor to suppress cell death”]…”.
Regarding claim 4, Ando teaches “a method for quickly and efficiently inducing RPE progenitor cells, comprising culturing stem cells using the RDM1 culture medium in the culture medium according to claim 1…” [Fig. 1, Ando also discloses the presence of both PAX6 and RPE65 where Ando states “[22]…wherein the culture period in the first step is a period sufficient for inducing gene expression of at least one of PAX6…and not more than 30 days” and Fig. 19 “…confirmation of the expression of retinal pigment epithelium markers RPE65…”].
Regarding claim 5, Ando teaches “the method according to claim 4, wherein the stem cells are selected from the group consisting of totipotent stem cells, pluripotent stem cells, and unipotent stem cells…” [Para starting with “[13] The production method according to any of the above mentioned…”].
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 following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim 10 is rejected under 35 U.S.C. §102(a)(1) as being anticipated by Meyer et al. [US 2017 067017 A1].
Regarding claim 10, Meyer et al. teaches a kit [¶ 0168] comprising at least one of the following substances: 1) a BMP signaling pathway inhibitor [¶ 0059], 2) a Wnt pathway inhibitor [¶ 0060], 3) an inhibitor of TGF-β [¶ 0060], 4) a ROCK inhibitor [¶ 0103].
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 6-9, 13-14, 17-20, 22, and 24 are rejected under 35 U.S.C. §103 as being unpatentable over Ando [US 2018 258388 A1], in view of Ye et al. [Reproducible production and image-based quality evaluation of retinal pigment epithelium sheets from human induced pluripotent stem cells, Sci Rep., 2020], in view of Choudhary et al. [Directing differentiation of pluripotent stem cells toward retinal pigment epithelium lineage].
Ando teaches each and every limitation in claims 1 and 4-5. Ando also teaches differentiating induced pluripotent stem cells into retinal pigment epithelial cells through successive culture stages, as discussed in claim 4 in the §102(a)(1) rejection.
Additionally for claim 6, Ando further teaches culturing cells obtained from an initial culture stage in a subsequent medium comprising Y-27632, a ROCK pathway inhibitor, thereby disclosing at least one of the alternative components [Para starting with “The medium to be used in the second step may optionally contain a ROCK…inhibitor”]. However, Ando does not expressly characterize the intermediate cells obtained during its differentiation process as RPE progenitor cells or pigment epithelial precursor cells.
For this limitation, Ye et al. teaches the stepwise differentiation of hiPSCs into RPE cells that include RPE progenitors at day 12, polygonal intermediate cells at day 24, and pigmented RPE cells at days 34-35 [Figure 1]. Ye et al. further teaches successive culture stages to promote the progressive differentiation of intermediate cells towards the RPE lineage [Id.].
Here, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Ando that discloses a multi-step culturing method for differentiating iPSCs into an RPE lineage with the further teachings of Ye et al. teaching that continued culturing of RPE progenitors produces subsequent intermediate RPE-lineage populations. The combination of Ando and Ye et al. represents the combination of known prior art elements according to known methods to yield predictable results given each reference teaches known signaling pathway modulators for inducing cells toward retinal pigment epithelial lineage and combining these known modulators would have predictably allowed each to perform its established pathway-modulating function therefore promoting the desired RPE differentiation. Given this, a person of ordinary skill would have a reasonable expectation of success because Ando already teaches the relevant medium components and sequential culturing steps while Ye et al. demonstrates the progression of RPE progenitors through subsequent development stages upon continued culturing. Furthermore, Ando teaching the differentiation of iPSCs into RPE cells through successive culture stages where Ye et al. teaches that RPE differentiation proceeds through an intermediate RPE progenitor stage, the production of such progenitor cells would reasonably be understood as an intermediate event in the differentiation process disclosed in Ando.
For claim 7 where Although Ando discloses the components listed in claim 7, it does not disclose the components as being included in the same culture medium. However, Ye et al. does disclose differentiating human induced pluripotent stem cells into retinal pigment epithelial cells through successive culture stages [Abstract, Fig. 1]. Furthermore, Ye et al. teaches changing the culture medium on day 18 to DMEM/F12 supplemented with KSR, N2 supplement and glutamine [RPE differentiation and RPE sheet production ¶ 1]. Ye et al. further discloses adding nicotinamide, a form of vitamin B3, from day 12 to day 24 in certain experiments [Id.]. With this, Ye et al. teaches a culture medium comprising DMEM/F12, KSR, N2 supplement, glutamine, and a vitamin.
For claim 8, Ando teaches every limitation for part 1) and part 2). However, Ando does not teach part 3) and part 4). For part 3), Ye et al. teaches a sequential culturing of hiPSCs differentiating into retinal pigment epithelial cells where the culture contains DMEM/F12 supplemented with KSR, N2 supplement and glutamine [RPE differentiation and RPE sheet production ¶ 1]. For part 4) however, Ye et al. does not teach the presence of β-mercaptoethanol. For this limitation, Choudhary et al. teaches the use of β-mercaptoethanol that is included in a culture medium containing DMEM, KSR-XF, GlutaMax™, and non-essential amino acid solution [Directed Differentiation of Pluripotent Stem Cells Toward RPE ¶ 1]. Here, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Ando that teaches differentiation of iPSCs into retinal progenitor epithelial cells with the teachings of both Ye et al. that discloses a sequential method for culturing iPSCs with the further teachings of Choudhary et al. that also discloses β-mercaptoethanol as a component included a culture medium that is similar to that disclosed by Ye et al. Additionally, 2-mercaptoethanol is known as a reducing agent commonly included in stem-cell culture media to maintain favorable redox environment, reduce oxidative stress, and support cell viability during culture and differentiation. The combination of Ando, Ye et al., and Choudhary et al. represents the combination of known prior-art elements according to known methods to yield predictable results given that Ye et al. teaches sequentially culturing hiPSCs toward a retinal pigment epithelial cell in a medium comprising DMEM/F12, KSR, N2 supplement, and glutamine, while Choudhary et al. teaches the use of β-mercaptoethanol and a non-amino acid solution in the same general context or directed differentiation of pluripotent stem cells toward RPE cells and would have led to predictable results by incorporating the known culture medium components of Choudhary et al. with the known culture components of both Ando and Ye et al. for the purpose of supporting retinal pigment epithelial differentiation.
Given this, a person skilled in the art would have a reasonable expectation of success of performing sequential culturing steps producing intermediate cell types where these intermediate cells types are further cultured in a medium using known components being used for their intended purpose allowing iPSCs to be cultured sequentially leading to the differentiation of the stem cells into mature retinal pigment epithelial cells as taught by both Ye et al. and Ando.
For claim 9 where the RDM2 culture medium contains at least one of a Wnt signaling pathway activator, a VEGFR kinase inhibitor, and a ROCK pathway inhibitor, Ye et al. teaches a method of differentiating hiPSCs into RPE cells using a culture medium comprising IWR-1-endo, SU5402, and Y-27632 in a sequential manner where these inhibitors are added where all three components are eventually present at the same time [See Fig 1].
For claim 14, where it is similar to claim 9, further adds the limitation the cells cultured in RDM2 are the same cells that were cultured in RDM1, Ando teaches the relevant RDM1 medium components and subsequently culturing the cells obtained from the initial culture stage in a second culture medium [Para starting with “That is, the present invention relates to the following”]. However, Ando does not expressly teach the RDM2 medium. However, Ye et al., as stated above in claim 9, teaches the use of a Wnt inhibitor, a VEGFR inhibitor, and ROCK inhibitor [Fig. 1]. Here, it would have been prima facie obvious to a person of ordinary skill in the art to prior to the filing of the claimed invention to modify the systems and methods of Ando that teaches a sequential culturing method for differentiating iPSCs into RPE cells with the additional teachings of Ye et al. that discloses a culture medium that contains a Wnt signaling pathway inhibitor, a VEGFR kinase inhibitor, and a ROCK inhibitor where Ye et a. also discloses the use of successive culturing. The combination of Ando and Ye et al. represents the combination of known prior art elements according to known methods to yield predictable results given each reference teaches known signaling pathway modulators for inducing cells toward retinal pigment epithelial lineage and combining these known modulators would have predictably allowed each to perform its established pathway-modulating function therefore promoting the desired RPE differentiation. Given this, there would have been a reasonable expectation of success for a person of ordinary skill to combine the teachings of Ando that discussed the use of each and every component and successive culturing with the additional teachings of Ye et al. that also disclose the particular culture medium components being used at different stages in the differentiation culture conditions in order to promote differentiation of iPSCs into RPE cells.
For claims 16-20 where the cells are prepared for use in a medicament for treating ophthalmic disease by either the method of claim 6 or 7, Ando teaches the use of such cells for treating numerous ophthalmic conditions [¶ 25]. Based on this, a person of ordinary skill would have a reasonable expectation of success of using the differentiated retinal pigment epithelial cells in a pharmaceutical composition given Ando expressly discloses these types of cells being used in treating ophthalmic diseases. Therefore, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the teachings of Ando that discloses methods for making retinal pigment epithelial cells with the further teachings of both Ye et al. and Chaudhary et al. that also disclose sequential culture methods for making retinal pigment epithelial cells from iPSCs that can then be used in a pharmaceutical composition for treating ophthalmic diseases based on the teachings of Ando. The combination of Ando, Ye et al., and Choudhary et al. represents the combination of known prior-art elements according to known methods yielding predictable results with the express teaching of culture conditions for producing retinal pigment epithelial cells with Ando expressly teaching the use of such cells in a medicament for treating ophthalmic disease where the preparation of these cells using the methods taught by Ando, Ye et al., and Choudhary et al. for therapeutic use would have predictably resulted in a medicament that comprises the derived retinal pigment epithelial cells for treating ophthalmic disease.
For claims 23 and 24, Ando teaches confirming the presence of both PAX6 and RPE65. Although, Ando does not specifically state at what percent or concentration level these markers are found, Ando does state “a period sufficient for inducing gene expression of at least one of PAX6…can be determined by confirming whether expression of at least one of these genes can be significantly detected…in a cell population after culturing for the period under the conditions” [Para starting with “Whether a given culture period under given culture conditions is”]. Based on this statement, a person of ordinary skill would understand that the culture conditions, as taught by Ando, would result in significant presence of certain cell markers that would result in a presence that makes up more than 20% and would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the teachings of Ando in view of Ye et al. and Choudhary et al. to optimize culture conditions that would lead to an increase proportion of cells expressing the desired marker characteristic based on culture conditions.
For claim 24, Choudhary et al. reports approximately 40-50% CRALBP-positive cells at an intermediate stage and greater than 90% CRALBP-positive cells in a later RPE population [Microarray profiling reveals stages of RPE development ¶ 4]. Choudhary et al. further describes a second replating step intened to increase RPE purity and reported high-purity cells expressing mature RPE markers that included ZO-1, PMEL17, and CRALBP [Generation of functional RPE cultures following a second replate step ¶ 1]. Furthermore, Ye et al. also teaches producing high-purity RPE sheets without manual selection disclosing ZO-1 protein expression along with increased RPE65, CRALBP, and PEDF expression relative to undifferentiated hiPSCs [Figure 3]. Additionally, the recitation that the cell population is prepared by the method of claim 8 constitutes a product-by-process language. The patentability of the claimed cell population is determined based on the resulting product itself. MPEP § 2113 states “[E]ven though product-by-process claims are limited by and defined by the process, determination of patentability is based on the product itself. The patentability of a product does not depend on its method of production. If the product in the product-by-process claim is the same as or obvious from a product of the prior art, the claim is unpatentable even though the prior product was made by a different process." In re Thorpe, 777 F.2d 695, 698, 227 USPQ 964, 966 (Fed. Cir. 1985.” Here, the cell population produced by the cited references are substantially identical to Applicant’s claimed population and differ only in the method used to differentiate the iPSCs into retinal pigment endothelial cells.
Here, it would have been prima facie obvious to a person of ordinary skill in the art prior to the filing of the claimed invention to modify the systems and methods of Ando that disclose a sequential culturing process for differentiating iPSCs into retinal pigment endothelial cells with the additional teachings of Ye et al. that also discuss differentiating iPSCs into retinal pigment endothelial cells with the addition of Choudhary et al. that discloses replating a heterogenous population of retinal pigment endothelial cells resulted in a population of differentiated cells expressing over 90% for CRALBP. In addition, Ye et al. disclosed producing the requisite cells with high-purity. Based on this, a person of ordinary skill would have been motivated to employ the teachings of Ando, Ye et al., and Choudhary et al. in order to obtain an induced retinal pigment endothelial cell population that displays a high percentage of ZO-1, RPE65, PAX6, and CRALBP in the cell population where the cell population expresses these markers at least 80% or more based on the teachings present in each of the cited references.
The Supreme court has acknowledged:
When a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one. If a person of ordinary skill can implement a predictable varition..103 likely bars its patentability…if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way, using the technique is obvious unless its actual application is beyond that person’s skill. A court must ask whether the improvement is more than the predictable use of prior-art elements according to their established functions…
…the combination of familiar elements according to known methods is likely to be obvious when it does no more than yield predictable results (see KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 U.S. 2007) emphasis added.
In KSR Int'l Co. v. Teleflex Inc., 550 U.S. 398 (2007), the Supreme Court reaffirmed "the conclusion that when a patent 'simply arranges old elements with each performing the same function it had been known to perform' and yields no more than one would expect from such an arrangement, the combination is obvious." Id. at 417 (quoting Sakraida v. Ag Pro, Inc., 425 U.S. 273,282 (1976)). The Supreme Court also emphasized a flexible approach to the obviousness question, stating that the analysis under 35 U.S.C. § 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the inferences and creative steps that a person of ordinary skill in the art would employ." Id. at 418; see also id. at 421 ("A person of ordinary skill is... a person of ordinary creativity, not an automaton.").
From the teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Conclusion
No claims allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JOHN DAVID MOORE whose telephone number is (703)756-1887. The examiner can normally be reached M-F 8-5.
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/JOHN DAVID MOORE/Examiner, Art Unit 1638
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631
