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 .
Election/Restrictions
Applicant’s election without traverse of the species of human RPE cells, to an atrophic retinas, dose of 50,000-1,000,000 cells and restore one or more retinal layers of the retina in the reply filed on 6/26/2025 is acknowledged. Upon further consideration the species requirements are withdrawn.
Claims 1-4, 6-11, 13-27, 29-30 and 35-37 are under consideration in the instant Office Action.
Withdrawn Rejections
The rejection of claims 1-4, 6-11, 13-18, 22-27, 29-30 and 35-37 under 35 U.S.C. 102(a)(1) & (a)(2) as being anticipated by Bohana-Kashtan et al. US2018/0016553 (8/11/2025 PTO-892) is withdrawn in view of applicant’s arguments being persuasive that the Bohana-Kashtan reference does not teach administering a cell therapeutic agent across a geographic atrophy (GA) to a subject having GA in need thereof.
The rejection of claims 1-4, 6-11, 13-30 and 35-37 under 35 U.S.C. 103 as being unpatentable over Bohana-Kashtan et al. US2018/0016553 (8/11/2025 PTO-892) in view of Da Cruz et al., 2018 (IDS 6/26/2025, #7) is withdrawn in view of applicant’s arguments being persuasive that the Bohana-Kashtan reference does not teach administering a cell therapeutic agent across a geographic atrophy (GA) to a subject having GA in need thereof.
New Rejections
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 23-24 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 1 requires administering a cell therapeutic agent across a geographic atrophy (GA) to a subject having GA in need thereof. Dependent claims 23-24 require delivering and implanting the RPE cells to a region of the retina. This limitation broadens the scope independent claim 1 since it reads on any region of the retina and not the GA region as now required in instant claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-4, 6-11, 13-30 and 35-37 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of treating a retinal disease in a subject having geographic atrophy (GA) by administering a pharmaceutical composition for treating or slowing the progression of a retinal disease across the GA, comprising between about 50,000 to 1,000,000 retinal pigment epithelium (RPE) cells wherein the administering comprises one or more of: implanting the RPE cells to an area covering a geographic atrophy (GA) lesion and RPE cells that express PEDF, wherein the RPE cells are generated by ex-vivo differentiation of human embryonic stem cells or generated by culturing human embryonic stem cells (hESCs) or induced pluripotent stem cells (iPSCs), does not reasonably provide enablement for a method of treating or slowing the progression of any retinal disease or disorder and restoring a plurality of retinal layers of a retina with any RPE cells. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure would require undue experimentation include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art and, (8) the breadth of the claims. In re Wands, 8 USPQ2d, 1400 (CAFC 1988).
With respect to claim breadth, the standard under 35 U.S.C. §112, first paragraph, entails the determination of what the claims recite and what the claims mean as a whole. As such, the broadest reasonable interpretation of the methods of claims 1, 13-18, 21, 26 and 35-37 is that any RPE in any retinal disease with GA can be used in a method to regenerate missing retinal layers and restore normal structures of a plurality of retinal layers, restores the fovea, restores functionality of photoreceptors in the retina and remodels the extracellular matrix of the retina. Therefore, the claims are directed to the treatment of any disease with GA with any RPE cell. The instant claims are broad and generic while what is enabled is narrow and specific. The prior art only provides examples of successfully treating GA in retina around the GA and not across the GA as now required by the instant claims. This treatment is targeted towards someone with age-related macular degeneration (AMD). While the treatment provides a benefit in the treating age-related macular degeneration (AMD) but does not provide evidence that all retinal disease with GA will be successfully treated any type RPE cell is capable of treating these patients. The instant specification does not provide any examples or evidence that this generic type of treatment would treat all GA retina related diseases. Further, the instant specification fails to teach any other possible agents that have the instantly claimed function and able regenerate retina and photoreceptor activity in retinas with GA. There is no support provided in the instant specification or in the prior or instant art that teaches or supports the ability to treating any retinal disease with any generic RPE cells.
The nature of the invention is clinical medicine comprising physiological modulation with an agent for a disorder of the central nervous system (CNS), and is therefore of the highest complexity due to the complex nature of the nervous system. The claim is equally unfettered by any limitation drawn to any means by which the physiological process step may be accomplished. Independent claim 1 is a “single means” claim in that it recites “any RPE cell that treats any retinal disease with GA” The instant fact pattern is similar to that in In re Hyatt, 798 F.2d 712, 218 USPQ 195 (Fed. Cir. 1983), wherein a single means claim which covered every conceivable means for achieving the stated purpose was held nonenabling for the scope of the claim because the specification at most disclosed only those means known to the inventors. In the instant case, the specification does provide working examples using the specific RPE cells treat AMD in subjects by administering the RPE cells across the GA lesion (see instant specification, Example 2, [0342-0347], [0350-351]). Independent claim 1 covers all possible RPE cells known or unknown as long as they are capable of treating retina with GA. Further, this claimed RPE cells encompasses any possible future discoveries of any cells with the claimed function. When claims depend on a recited property (treating a neuron disease), a fact situation comparable to Hyatt is possible, where the claim covers every conceivable structure (means) for achieving the stated property (result) while the specification discloses at most only those known to the inventor. See also Fiers v. Sugano, 984 F.2d 164, 25 USPQ2d 1601 (Fed. Cir. 1993) and MPEP §2164.08(a). Therefore, the specification fails to provide enough guidance for one skilled in the art on how to practice the instant method, thereby requiring trial and error experimentation to identify compounds meeting the functional limitations of the claims. The dependent claims narrow the scope to specific RPE lineage (claims 2-4) but still covers all possible RPE cells known or unknown as long as they are capable of treating GA in the retina. The prior art does not provide compensatory teachings. The art teaches a limited amount of possible RPE cells to produce the required effect as discussed below; see Bohana-Kashtan et al. US2018/0016553 (8/11/2025 PTO-892), who teaches a pharmaceutical composition comprising human embryonic stem cell (hESC) derived RPE cells (hESC-RPE cells) or induced pluripotent stem cell (iPSC)-derived RPE cells for treating or slowing the progression of a retinal disease or disorder including dry AMD and macular degeneration, wherein the RPE cells is between 50-100x103 or 25-200x103 per dose or 70x103 or 250x103 per 100ul (see paragraphs [0002]-[0007]; [0003]; [0104]; [0114]; [0009]; [0021]-[0023]; [0031]-[0061]; [0082]; [0084]; [0088]; [0104]-[0108]; [0111]-[0118]; [0131]-[0139]; [0142]-[0143]; [0150]-[0221]; [0231]-[0249]; [0267]-[0357]; [0390]; [0431]; examples 1-4; [0407]-[0428]; p. 21-23, example 6; p. 25-29, examples 8-10; p. 29-30, claims 1-2, 10, 25, 28, 30-32, 35, 37-38, 41 and 45, in particular). Bohana-Kashtan teaches a method of treating or slowing the progression of a retinal disease or disorder including dry AMD, the method comprising administering, transplanting or implanting a therapeutically effective amount of a pharmaceutical composition comprising human embryonic stem cell derived RPE cells (hESC-RPE cells) or induced pluripotent stem cell derived RPE cells (iPSC-RPE cells) to a subject with AMD or dry AMD by delivering, transplanting or implanting the RPE cells into the target sites or the subretinal space of patients with retinal diseases including dry AMD, via direct injection, subretinal injection or via a trans-scleral, trans-choroidal approaches or direct trans-scleral injection into the vitreal space or delivery to the anterior retinal periphery in proximity to the ciliary body or is introduced into the target site (see paragraphs [0248]-[0250]; [0251]-[0253]); [0449]; [0003]; [0104]-[0108]; [0111]-[0114], p. 20-25, examples 5-7; p. claims 1, 25, 28, 30-32, 35, 37-38, 41 and 45, in particular). Bohana-Kashtan teaches patients with dry AMD have geographic atrophy (GA) with degeneration of RPE cells and photoreceptors over large areas of the macula. Bohana-Kashtan teaches the amount of RPE cells is 25x103, 100x103, 200x103, 50x103 or 100x103 or 25-200x103 per dose in 2ul and that the RPE cells express PEDF at effective levels above 2000ng/ml/day (see paragraphs [0137]; ]; [0143], [0231]). Bohana-Kashtan also teaches that the RPE cells are generated by ex-vivo differentiation of pluripotent stem cells including human embryonic stem cells (hESCs) or generated by culturing hESCs or induced pluripotent stem cells (iPSCs) in a medium comprising nicotinamide to generate differentiating cells; (b) culturing the differentiating cells in a medium comprising nicotinamide and activin A to generate cells further differentiated towards the RPE lineage; and (c) culturing the cells further differentiated towards the RPE lineage (see paragraphs [0031]-[0062]; [0150]-[0248]; p. 30, claims 25, 32, 35, 37-38, 41). Bohana-Kashtan and the prior art fails to teach delivering the RPE cells directly across the GA lesion.
Also see Da Cruz et al., 2018 (IDS 6/26/2025, #7), which teaches treating age-related macular degeneration (AMD) by administering fully differentiated, human embryonic stem cell (hESC)-derived RPE on a patch (see abstract). Da Cruz teaches that this treatment lead to visual acuity gain of 29 and 21 letters in two patients (see abstract). Da Cruz teaches visual recovery with RPE treatment and the use of microperimetry to observed these effects on the retina and RPE (see page 9-10, lines 290-310) but fails to teach the intended results of the instant claims of regeneration and restructure.
There is still a lot of unknown in the art of what are all the possible RPE cells that are functionally capable of meeting the functional imitations of the instant claims and would still require undue experimentation to determine what these RPE cells are and what specific retinal disease with GA will actually result in the required structural and functional changes. One of ordinary skill would also have to take into account what type of neurons (photoreceptor neurons are specialized neurons) this agent is being administered to, to be able to determine if the agent meets the required function of the instantly claimed agent. This would require undue experimentation. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without such guidance, the changes which can be made and still maintain activity/utility is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See Ex parte Forman, 230 USPQ 546 (Bd. Pat. App. & Int. 1986).
As set forth above, inadequate guidance is presented in the specification to overcome the obstacles in practicing the claimed invention in its full scope. The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue. Given the limited examples of limited description of the claimed RPE cells and the tremendous breath of scope involving the instant claims of what retinal diseases are encompassed and the required structural and functional changes, it would require undue experimentation for one of skill in the art to practice the claimed invention in its full scope. Therefore, the specification fails to provide enough guidance for one skilled in the art on how to practice the instant method, thereby requiring trial and error experimentation to identify compounds and diseases that would meet the functional limitations of the claims. The general knowledge and level of skill in the art do not supplement the omitted description because specific, not general, guidance is what is needed.
Therefore, claims 1-4, 6-11, 13-30 and 35-37 are rejected.
Maintained Rejection
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 1-4, 6-11, 13-27, 29-30 and 35-37 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 88, 90-94, 98-105, 116-122 of copending Application No. 16/494,498. The claims of ‘498 encompass using a pluripotent stem cell derived RPE for treating retinal damage, slowing the progression of retinal damage, preventing retinal damage, replacing retinal tissue and restoring damaged retinal tissue, comprising the pluripotent stem cell derived retinal tissue graft comprising RPE cells to the GA area.
This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
Response to Arguments
Applicant's arguments filed 3/23/2026 have been fully considered but they are not found persuasive. Applicant's request that the double patenting rejection of the instant claims over of the application be held in abeyance until there is allowable subject matter, at which time they will consider responding is not appropriate. Since applicant has not provided any objections or arguments for the double patenting rejections of record, the above double patenting rejections are maintained.
Conclusion
No claims are allowed.
Advisory Information
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/AURORA M FONTAINHAS/Primary Examiner, Art Unit 1675
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