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 .
This action is responsive to papers filed 09/02/2025.
Claims 6-9, 12, 16, 20, and 22 have been previously canceled, claims 1-5, 10-11, 13-15, 17-19, 21, and 23-25 have been newly canceled and claims 35-42 have been newly added.
Claims 26-42 are currently pending.
Election/Restrictions
Applicant’s election without traverse of Group II (claims 26-34) in the reply filed on 09/02/2025 is acknowledged.
Applicant’s election of “conditioned media” as the species in the reply filed on 09/02/2025 is also acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the species restriction requirement, this election has been treated as an election without traverse as well (MPEP § 818.01(a)).
Claims 29, 31-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 09/02/2025.
Claims 26-28, 30, and 35-42 have been examined on their merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 11/22/2022 has been considered by the examiner.
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Claim Objections
Claims 27, 35, 42 are objected to because of the following informalities:
Claim 27 has the wrong claim status has it has not been withdrawn. The species requirement was for the election of the type of fibroblast-derived product, not between fibroblast and fibroblast-derived product.
Claim 35 recites the abbreviation of RPE and claim 42 recites the abbreviations CNTF, HGF and BDNF.
An abbreviation should be preceded in its first occurrence by the specific identity of the entity which said abbreviation is intended to represent. Thereafter, the use of the abbreviation in the claims will be understood.
Appropriate correction is required.
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 26-28, 30, and 35-42 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 the treating of blindness or macular degeneration, does not reasonably provide enablement for the prevention of blindness or macular degeneration.
The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to carry out the methods of the invention commensurate in scope with these claims.
The claims are drawn to methods of treating or preventing blindness or macular degeneration in a subject comprising providing to the subject a therapeutically effective amount of fibroblasts or fibroblast-derived products.
There are numerous causes for blindness including eye disorders, eye injuries, birth defects, age-related diseases such as macular degeneration, cataracts and glaucoma (MedlinePlus-1 2024, “Vision Impairment and blindness” page 1 and MedlinePlus-2 2024, “Blindness and vision loss” pages 1-4). Age-related macular degeneration (AMD) represents the leading cause of irreversible blindness in elderly people, mostly after the age of 65, and results in the progressive deterioration of visual function in patients. The current therapeutic options are only partially able to slow down the natural course of the disease, without being capable of stopping its progression (DiCarlo et al 2021, abstract). There is currently no cure for Age-related Macular Degeneration (Fernandez-Robredo et al, 2014, abstract).
Applicant has not provided any evidence that the claimed method would be able to prevent blindness and/or macular degeneration that was caused by any and all situations.
Further, the burden of enabling "prophylaxis" (i.e. prevention), of a disease is greater than that of enabling a treatment method due to the need to screen the subjects susceptible to the respective condition and the difficulty of proof that the administration of the composition was the agent that acted to prevent the condition.
Given that the outcomes of practicing the claimed methods beyond the scope defined above are highly unpredictable, and that the disclosure does not provide sufficient direction, guidance or working examples, the experimentation left to those skilled in the art is extremely extensive. It would initially require experimentation in animal models of the numerous diseases which are within the scope of the claims, using numerous types and subtypes of cells derived from fibroblasts, under various dosing regimens. The number of possible permutations of these parameters is so large that, even in cases where the requisite methods are routine, the amount of experimentation is beyond the capacity of even the largest research institutions. Since the skilled artisan understands that, for the reasons addressed above, the chances of identifying a set of conditions resulting in a useful outcome are extremely low, the skilled artisan would reasonably view such experimentation as unnecessarily, and improperly, extensive and undue.
Therefore, the currently claimed methods are not fully enabled for their entire scope based on the specification and what is known in the art of blindness and macular degeneration.
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 35-40 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 35 recites the limitation "the conditioned media" in line 1. There is insufficient antecedent basis for this limitation in the claim as the parent claim 26 which claim 35 is dependent upon does not recite “a conditioned media” and thus the metes and bounds of the claim are indefinite.
In addition, claim 35 recites wherein the conditioned media can comprise “a supernatant from cultured RPE cells or progenitors thereof”.
It is unclear how conditioned media from fibroblasts can comprise a supernatant from cultured RPE cells or progenitors thereof without an active method step for transferring this supernatant from the RPE culture to the fibroblast culture.
Claim 36 recites the limitation "the one or more fibroblast cells in a culture" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim as the parent claims 26 and 35 which claim 36 is dependent upon do not recite “one or more fibroblast cells” and thus the metes and bounds of the claim are indefinite.
Because claims 36-40 depend from indefinite claim 35 and do not clarify the point of confusion, they must also be rejected under 35 U.S.C. 112, second paragraph.
For examination purposes claims 35-40 will be examined as if they were dependent upon claim 30.
Appropriate correction is required.
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.
Claim(s) 26-28, 30, and 41-42 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Uteza et al (Proc. Natl. Acad. Sci. 1999) as evidenced by Rong et al (US 5,871,959).
Regarding claims 26-28, 30 and 41, Uteza disclose a method of treating blindness (loss of vision) by administering encapsulated fibroblasts to the eyes of RCS rats (rats with defective retinal-pigment epithelial cells)(abstract, pages 3126-3127). These encapsulated fibroblasts secrete hFGF-2 that provoked a local delay of photoreceptor degeneration (abstract, pages 3126-3128, page 3131). Since the encapsulated fibroblasts are suspended in growth medium prior to encapsulation (page 3127) and release hFGF-2 from the microcapsules after transplantation (page 3129-3131) the administration of these encapsulated fibroblasts is also deemed to comprise the administration of conditioned media derived from fibroblasts.
Regarding claim 42, Uteza NIH fibroblasts inherently express HGF into their conditioned media as evidenced by Rong (column 24).
Therefore, the teaching of Uteza et al anticipates Applicant’s invention as claimed.
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.
Claim(s) 35 is rejected under 35 U.S.C. 103 as being unpatentable over Uteza et al (Proc. Natl. Acad. Sci. 1999) as evidenced by Rong et al (US 5,871,959) and as applied to claims 26-28, 30, and 41-42 above and further in view of Marban et al (WO 2014/028493).
Regarding claim 35, Uteza teaches the claimed method as described above, but are silent to the presence of concentrated exosomes in the conditioned medium of the administered fibroblasts.
However, Uteza specifically suggest that other agents can be applied as potential therapeutic tools to treat retinal dystrophies (abstract) also including other stably transfected cell lines that secrete several trophic factors (page 3131, column 2).
Marban disclose methods and compositions to repair and/or regenerate tissue that has been damaged due to injury or disease by administering exosomes that have been secreted by regenerative cells (page 2 para 5-6). These exosomes may be obtained from cultured fibroblasts and concentrated (page 26 para 82).
One of ordinary skill in the art would have been motivated to include exosomes concentrated from the regenerative fibroblasts used in Uteza in their administered composition for the treatment of vision loss (blindness) caused by photoreceptor degeneration because Marban teach and suggest that the administration of exosomes secreted and concentrated from the culture media of fibroblasts (conditioned media) is beneficial for the repair and regeneration of damaged tissue and because Uteza specifically suggest that other agents can be applied as potential therapeutic tools to treat retinal dystrophies (abstract). One of ordinary skill in the art would have had a reasonable expectation of success because Uteza also teach and suggest that including other stably transfected cell lines that secrete several trophic factors is desirable as well (page 3131, column 2).
Therefore, the combined teachings of Uteza et al and Marban et al render obvious Applicant’s invention as claimed.
Claim(s) 36-40 are rejected under 35 U.S.C. 103 as being unpatentable over Uteza et al (Proc. Natl. Acad. Sci. 1999) as evidenced by Rong et al (US 5,871,959) in view of Marban et al (WO 2014/028493) as applied to claims 26-28, 30, 35, and 41-42 above and further in view of Chavala et al (WO 2018/232258).
Regarding claims 36-40, the combined teachings of Uteza et al and Marban et al render obvious Applicant’s invention as described above, but do not specifically include further culturing the one or more fibroblast cells in a culture to produce one or more differentiated RPE cells (retinal pigmented epithelial cells)
However, Uteza specifically suggest that other agents can be applied as potential therapeutic tools to treat retinal dystrophies (abstract) also including other stably transfected cell lines that secrete several trophic factors (page 3131, column 2).
Chavala disclose methods and compositions for reprogramming somatic cells to retinal cells for use in cell replacement therapy to treat such as vision loss (blindness) (pages 1-2 para 5). Fibroblasts are converted to chemically induced photoreceptor cells or chemically induced retinal pigment epithelium cells (ciRPE) (differentiated RPE cells)(page 2 para 7). Agents capable of inducing this fibroblast conversion (differentiation) to RPE include epigenetic modifier valproic acid (page 3 para 9, page 5 para 16-18, page 43 claim 3 claim 7). The culture can include a biocompatible substrate that allows the cells to grow including hyaluronic acid (pages 25-26 para 113). Characteristics of a retinal pigment epithelium cell include RPE65, Bestrophin and phagocytosis (page 25 para 110).
One of ordinary skill in the art would have been motivated to further include RPE cells cultured from the fibroblasts in Uteza in their administered composition for the treatment of vision loss (blindness) caused by photoreceptor degeneration because Chavala teach and suggest that this is suitable and beneficial for the treatment of vision loss (blindness) in cell replacement therapy and because Uteza specifically suggest that other agents can be applied as potential therapeutic tools to treat retinal dystrophies (abstract). The use of valproic acid and hyaluronic acid in this conversion method would have been motivated by Chavala’s teaching that these are beneficial additives for this conversion (differentiation) process. Utilizing RPE cells that have the expected properties of endogenous RPE cells, such as expression of RPE65, bestrophin and capability of phagocytosis, would have been motivated as well because Chavala also suggest that these are beneficial and desirable as well. One of ordinary skill in the art would have had a reasonable expectation of success because Uteza also teach and suggest that including other stably transfected cell lines that secrete several trophic factors is desirable as well (page 3131, column 2).
Therefore, the combined teachings of Uteza et al, Marban et al and Chavala et al render obvious Applicant’s invention as claimed.
Conclusion
No claims are allowed.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Kleinsek et al., “Methods and Compositions for Organ and Tissue Functionality”, US 2007/0128174, (page 76 claim 15).
O’Heeron et al., “Methods of Enhancing Fibroblast Therapeutic Activity”, US 2018/0195044, (para 29 and para 63).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAURA J SCHUBERG whose telephone number is (571)272-3347. The examiner can normally be reached 8:30-5:00 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, James (Doug) Schultz can be reached at 571-272-0763. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
LAURA J. SCHUBERG
Primary Examiner
Art Unit 1631
/LAURA SCHUBERG/Primary Examiner, Art Unit 1631