DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims 109-142, of record 4/17/2025, are pending and subject to prosecution.
Priority
The instant application is a CON of 17/049018 (US patent no. 12110503, filed 10/19/2020), which is a national stage entry of PCT/US2019/028557 (filed 4/22/2019), which claims benefit of provisional application 62/660899 (Filed 4/20/2018).
Claim Interpretation
Claim 125 recites the limitation “a pharmaceutically acceptable carrier”, which is not defined by the instant specification. The broadest reasonable interpretation is therefore considered to be any carrier that would not cause significant harm upon administration.
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.
Claims 109-115 and 118 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a judicial exception (i.e., a law of nature, a natural phenomenon, or an abstract idea) without significantly more.
Regarding claims 109-115 and 118: Claims 109-115 and 118 are directed to a composition comprising photoreceptor precursor cells, wherein various percentages of the cells express certain markers.
Step 1: Each claim is directed to a composition comprising photoreceptor precursor cells, which is a statutory category of matter (Step 1: YES).
Step 2A, prong 1: Photoreceptor precursor cells are nature-based products. When a claimed composition includes a nature-based product, further analysis is taken to determine if the claimed composition recites a nature-based product judicial exception by comparing the claimed composition to the closest naturally occurring counterpart to determine if the claimed composition has markedly different characteristics than the counterpart.
The closest naturally occurring counterpart of photoreceptor precursor cells, wherein at least 50%, 70%, 80%, 85%, or 90% of the cells express recoverin; less than 15% or 10% of the PRPs express PAX6; at least 90% of the cells express TUBB3; and the cells express CRX, is considered to be naturally occurring photoreceptor precursor cells. Lakowski et al. teach identification of photoreceptor precursor cells on the basis of Crx and recoverin co-expression (See page 715, col. 1, ¶1 and fig. 2-4), indicating that the photoreceptor precursor cells would necessarily be recoverin-positive and CRX-positive. Belecky-Adams et al. teach that Pax6 is not detected in prospective photoreceptors (See Abstract and page 1297, col. 2, full ¶1-3). Wiley et al. teach that photoreceptor precursor cells show nearly complete staining with an anti-beta-tubulin III antibody (which reads on “at least 90% of the PRPs express TUBB3”) (See page 5, full ¶1 and fig. 3E-F). The claims therefore recite product of nature judicial exceptions (Step 2, prong 1: YES)
Step 2A, prong 2: Each claim is directed to a product and does not recite any structure that serves to integrate the compositions into a practical application (Step 2, prong 2: NO).
Step 2B: There are no additional elements required by the claims.
Claims 109-115 and 118 do not qualify as eligible subject matter and are rejected under 35 U.S.C. 101.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 109-116, 118, 121-122, 125-133, 135, and 139-140 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Lakowski et al. (Stem Cells, 2018), of record in IDS dated 11/1/2024, as evidenced by Belecky-Adams et al. (Investigative Ophthalmology & Visual Science, 1997), Wiley et al. (Scientific Reports, 2016), and Katoh et al. (Journal of Neuroscience, 2010).
Regarding claims 109-114, 118, 121-122, 125-131, 135, and 139-140: Lakowski et al. teach the generation of photoreceptor precursor cells from human ESCs and iPSCs (which reads on “human photoreceptor precursor cells”) (See Abstract). The stem cells were grown as aggregates/embryoid bodies in media (which reads on “a composition” and “a pharmaceutically acceptable carrier”) on a laminin-coated surface (which reads on “adhered onto an extracellular matrix) and differentiated into retinal cells (See page 710, col. 2, full ¶3). The differentiated cells were transplanted into the subretinal space of retinal degeneration (which reads on “retinal disease”) model mice (See page 719, col. 1, full ¶1). Photoreceptor precursor cells in the aggregates were identified on the basis of Crx and recoverin co-expression (See page 715, col. 1, ¶1 and fig. 2-4), indicating that the photoreceptor precursor cells would necessarily be recoverin-positive (which reads on “at least 50% of the PRPs express RCVRN”, “at least 70% of the PRPs express RCVRN”, “at least 80% of the PRPs express RCVRN”, “at least 85% of the PRPs express RCVRN”, and “at least 90% of the PRPs express RCVRN”) and CRX-positive (which reads on “the PRPs express… CRX”). Lakowski et al. teach that the cell aggregates express Pax6 but are silent on Pax6 expression specifically in photoreceptor precursor cells.
The teachings of Belecky-Adams et al. are cited as evidence showing that Pax6 is not detected in prospective photoreceptors (See Abstract and page 1297, col. 2, full ¶1-3). Thus, the cells of Lakowski et al. necessarily read on “less than 15% of the PRPs express PAX6” and “less than 10% of the PRPs express PAX6”.
Regarding claims 115 and 132: Following the discussion of claims 109-114, 118, 121-122, 125-131, 135, and 139-140, Lakowski et al. do not expressly teach TUBB3 expression specifically in photoreceptor precursor cells.
The teachings of Wiley et al. are cited as evidence showing the production of iPSC-derived photoreceptor precursor cells (See Abstract). Organoids comprising photoreceptor precursor cells show expression of recoverin, and nearly every cell appears to stain with the anti-beta-tubulin III antibody Tuj1 (which reads on “at least 90% of the PRPs express TUBB3”) (See page 5, full ¶1 and fig. 3E-F). Thus, the cells of Lakowski et al. necessarily comprise photoreceptor precursor cells that read on “at least 90% of the PRPs express TUBB3”.
Regarding claims 116 and 133: Following the discussion of claims 109-114, 118, 121-122, 125-131, 135, and 139-140, Lakowski et al. do not expressly teach CHX10 expression specifically in photoreceptor precursor cells.
The teachings of Katoh et al. are cited as evidence that photoreceptor precursors, as detected by rhodopsin expression, do not appear to express CHX10 (See fig. 3E). Thus, the cells of Lakowski et al. necessarily comprise photoreceptor precursor cells that read on “less than 15% of the PRPs express CHX10”.
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.
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.
Claims 109-116, 118, 121-122, 124-133, 135, and 139-140 are rejected under 35 U.S.C. 103 as being unpatentable over Lakowski et al. (Stem Cells, 2018), of record, as evidenced by Belecky-Adams et al. (Investigative Ophthalmology & Visual Science, 1997), Wiley et al. (Scientific Reports, 2016), and Katoh et al. (Journal of Neuroscience, 2010).
The teachings of Lakowski et al., Belecky-Adams et al., Wiley et al., and Katoh et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claim 124: Following the discussion of claims 109-116, 118, 121-122, 125-133, 135, and 139-140, Lakowski et al., evidenced by Belecky-Adams et al., Wiley et al., and Katoh et al., teach a composition comprising photoreceptor precursor cells and its use in a mouse retinal degeneration model but do not expressly teach its use in treating specific retinal disorders.
However, Lakowski et al. teach that degenerative conditions affecting photoreceptors include age-related macular degeneration and retinitis pigmentosa (See page 709, col. 2, 1). One of ordinary skill in the art would therefore have found it obvious to apply the method of Lakowski et al. to the treatment of age-related macular degeneration and retinitis pigmentosa because they demonstrate that transplanted photoreceptors can engraft in and potentially rescue a mouse model of general retinal degradation (See page 720, col. 2, full 1).
Claims 109-116, 118, 121-122, 124-133, 135, and 138-140 are rejected under 35 U.S.C. 103 as being unpatentable over Lakowski et al. (Stem Cells, 2018), of record, as evidenced by Belecky-Adams et al. (Investigative Ophthalmology & Visual Science, 1997), Wiley et al. (Scientific Reports, 2016), and Katoh et al. (Journal of Neuroscience, 2010), in view of Yanai et al. (Methods in Molecular Biology, 2015).
The teachings of Lakowski et al., Belecky-Adams et al., Wiley et al., and Katoh et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claim 138: Following the discussion of claims 109-116, 118, 121-122, 125-133, 135, and 139-140, Lakowski et al., evidenced by Belecky-Adams et al., Wiley et al., and Katoh et al., teach a composition comprising photoreceptor precursor cells and its use in a mouse retinal degeneration model but do not expressly teach adding a cryoprotectant to the cells.
Yanai et al. teach the generation of photoreceptor precursor cells originating from ESC-derived embryoid bodies (See Abstract and section 3.3.3). Yanai et al. teach that the cells can be frozen in photoreceptor precursor cell medium containing 10% DMSO (which reads on “a cryoprotectant”) for future use (See page 364, section 3.3.3).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the composition of Lakowski et al., as evidenced by Belecky-Adams et al., Wiley et al., and Katoh et al., to comprise a photoreceptor precursor medium comprising DMSO, such as is taught by Yanai et al. One would be motivated to make this modification in order to use the cells at future time points. There would be a reasonable expectation of success in doing so because Yanai et al. teach that photoreceptor cells can be frozen in such a manner (See page 364, section 3.3.3).
Claims 109-116, 118, 121-122, 124-133, 135, and 139-142 are rejected under 35 U.S.C. 103 as being unpatentable over Lakowski et al. (Stem Cells, 2018), of record, as evidenced by Belecky-Adams et al. (Investigative Ophthalmology & Visual Science, 1997), Wiley et al. (Scientific Reports, 2016), and Katoh et al. (Journal of Neuroscience, 2010), in view of Mandai et al. (US 12285543 B2).
The teachings of Lakowski et al., Belecky-Adams et al., Wiley et al., and Katoh et al. are set forth in the rejection above and are incorporated herein in their entirety.
Regarding claims 141-142: Following the discussion of claims 109-116, 118, 121-122, 125-133, 135, and 139-140, Lakowski et al., evidenced by Belecky-Adams et al., Wiley et al., and Katoh et al., teach a composition comprising photoreceptor precursor cells and its use in a mouse retinal degeneration model but do not expressly teach transplantation of the cells in the form of clusters rather than dissociated cells.
Mandai et al. teach retinal cell populations for transplantation (See Abstract). The cell population can comprise photoreceptor precursor cells (See col. 3, line 52-56 and 66-67 and col. 4, line 1-4). The cell population can be transplanted in the form of an aggregate (See col. 29, line 63-64).
It would have been obvious to one having ordinary skill in the art prior to the effective filing date of the claimed invention to modify the method of Lakowski et al., evidenced by Belecky-Adams et al., Wiley et al., and Katoh et al., to comprise administration of the photoreceptor precursor cells as aggregates. One would have been motivated to make this modification because Mandai et al. teach that cell populations comprising photoreceptor precursors can be transplanted in aggregate form (See col. 3, line 52-56 and 66-67; col. 4, line 1-4; and col. 29, line 63-64). There would be a reasonable expectation of success in doing so because such a modification could be readily performed.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP 2159. See MPEP 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 109-114, 116, 119, 121-122, 125-131, 133, 136, and 138 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 93-94, 100-103, 105, 108-110, 113, and 120-122 of co-pending Application No. 19235357 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because of the following reasons.
Regarding claims 109-114, 116, 119, 121-122, 125-131, 133, 136, and 138: Co-pending claim 93 recites a composition comprising human photoreceptor precursor cells (PRPs), wherein the composition comprises: NR2E3+ cells and between at least 20% to 60% PPP4R4+ cells, and less than or equal to 0.5 copies of vimentin (VIM) per copy of Succinate Dehydrogenase Complex Flavoprotein Subunit A (SDHA), and wherein the PRPs are derived from induced pluripotent stem cells (iPSCs). Co-pending claim 94 recites the composition according to co-pending claim 93, wherein the human PRPs comprise: at least 90% AIPL1+ cells; at least 90% RCVRN+ cells; less than or equal to 7% PAX6+ cells; less than or equal to 7% CHX10+ cells; less than or equal to 0.5% (which reads on “essentially no expression”) TYRP1+ cells; and less than or equal to 0.5% (which reads on “essentially no expression”) Ki67+ cells.
Co-pending claim 100 recites a composition comprising PRPs, wherein the composition comprises cell aggregates, wherein the cell aggregates have a median diameter of about 30 µm to about 65 µm. Co-pending claim 101 recites the composition according to co-pending claim 100, wherein the PRPs are in a single cell form, an aggregate cell form, or both. Co-pending claim 102 recites the composition according to co-pending claim 101, wherein the PRPs comprise: NR2E3+ cells and between at least 20% to 60% PPP4R4+ cells, and less than or equal to about 0.5 copies of VIM per copy of SDHA. Co-pending claim 103 recites composition according to co-pending claim 102, wherein the PRPs further comprise: at least about 90% AIPL1+ cells; at least about 90% RCVRN+ cells; less than or equal to about 7% PAX6+ cells; less than or equal to about 7% CHX10+ cells; less than or equal to about 0.5% (which reads on “essentially no expression”) TYRP1+ cells; and less than or equal to about 0.5% (which reads on “essentially no expression”) Ki67+ cells.
Co-pending claim 108 recites a composition comprising human PRPs and balanced salt solution buffer supplemented with 0.2% human serum albumin (HSA) (which reads on “a pharmaceutically acceptable carrier”). Co-pending claim 109 recites the composition according to co-pending claim 108, wherein the balanced salt solution buffer comprises about 0.10 to 1.50 mg/ml of magnesium chloride, about 0.10 mg/ml to about 1.5 mg/ml of calcium chloride, about 0.10 mg/ml to about 1.5 mg/ml of potassium chloride, about 0.10 mg/mL to about 3.0 mg/ml of sodium citrate, about 0.10 mg/mL to about 6.0 mg/ml of sodium acetate, and about 0. 10 mg/mL to about 10.0 mg/mL of sodium chloride. Co-pending claim 110 recites the composition according to co-pending claim 109, wherein the balanced salt solution buffer comprises 0.3 mg/ml of magnesium chloride, 0.48 mg/ml of calcium chloride, 0.75 mg/ml of potassium chloride, 1.7 mg/ml of sodium citrate, 3.9 mg/ml of sodium acetate, and 6.4 mg/ml of sodium chloride. Co-pending claim 113 recites the composition according to co-pending claim 110, wherein the human PRPs comprise NR2E3+ cells and between at least 20% to 60% PPP4R4+ cells, and less than or equal to about 0.5 copies of VIM per copy of SDHA. Co-pending claim 113 recites the composition according to co-pending claim 113, wherein the human PRPs further comprise: at least about 90% AIPL1+ cells; at least about 90% RCVRN+ cells; less than or equal to about 7% PAX6+ cells; less than or equal to about 7% CHX10+ cells; less than or equal to about 0.5% TYRP1+ cells; and less than or equal to about 0.5% Ki67+ cells.
Co-pending claim 120 recites a composition comprising human PRPs and a cryopreservant solution. Co-pending claim 121 recites the composition of co-pending claim 120, wherein the cryopreservant solution comprises adenosine, dextran-40, lactobionic acid, HEPES, sodium hydroxide, potassium chloride, potassium bicarbonate, potassium phosphate, dextrose, sucrose, mannitol, calcium chloride, magnesium chloride, potassium hydroxide, L-glutathione, DMSO, and water. Co-pending claim 122 recites the composition according to co-pending claim 121, wherein the human PRPs comprise NR2E3+ cells and between at least 20% to 60% PPP4R4+ cells, and less than or equal to about 0.5 copies of VIM per copy of SDHA, wherein the human PRPs further comprise: at least about 90% AIPL1+ cells; at least about 90% RCVRN+ cells; less than or equal to about 7% PAX6+ cells; less than or equal to about 7% CHX10+ cells; less than or equal to about 0.5% TYRP1+ cells; and less than or equal to about 0.5% Ki67+ cells, and wherein the composition has a percentage viability of at least about 50%.
Co-pending claims 94, 103, 113, and 122 are directed to species of the generic instant claims. Because a species will anticipate a claim to a genus, the co-pending claims anticipate the instant claims.
Regarding claim 139: Following the discussion of claims 109-114, 116, 119, 121-122, 125-131, 133, 136, and 138, co-pending claim 105 recites the composition according to co-pending claim 104, wherein the PRPs are derived from human pluripotent stem cells (PSCs) or human induced pluripotent stem cells (iPSCs). The co-pending claim anticipates the instant claim.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Claims 117, 120, 134, and 137 are objected to as being dependent upon a rejected base claim but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter:
The prior art appears to indicate that ONECUT1 is normally expressed in photoreceptor precursor cells (See Muranishi et al. fig. 4B).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER S SPENCE, whose telephone number is 571-272-8590. The examiner can normally be reached M-F 8:30-5:30.
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/JENNIFER S SPENCE/Examiner, Art Unit 1633
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