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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 22 June 2026 has been entered.
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 22 June 2026.
CLAIMS UNDER EXAMINATION
Claims 1-3 and 6-9 have been examined on their merits.
PRIORITY
Provisional Application 62/819160, filed on 15 March 2019, is acknowledged.
REJECTIONS
Claim Rejections - 35 USC § 101
Claims 1-3 and 6-9 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 as evidenced by Gagliardi et al. (Characterization and Transplantation of CD73-Positive Photoreceptors Isolated from Human iPSC-Derived Retinal Organoids
Stem Cell Reports, 2018; 11, 665-680) and Eldred et al. (Thyroid hormone signaling specifies cone subtypes in human retinal organoids. Science 362,eaau 6348 (2018).
Question 1: Are the claims directed to a process, machine manufacture or composition of matter? Yes, claim 1 is directed to a composition of matter.
Question 2A: Are the claims directed to a product of nature, a law of nature, a natural phenomenon, or an abstract idea (judicially recognized exceptions) ?
Prong 1. Yes, claim 1 is directed to a nature-based product limitation. The limitation in the claim that sets forth a nature based product is: a population of cells which are CD73+, THRB+, CD11b-, which are characterized by expression of cone arrestin and red/green opsin and absence of rhodopsin.
The closest naturally occurring counterpart is a red/green cone photoreceptor. As evidenced by Gagliardi: Photoreceptors express CD73+ (see page 666, left column, second paragraph). Cones express cone arrestin (see page 666, right column, seventh line from the bottom). Red/green cones express OPN1W/M (red/green opsin) (page 671, left column, second paragraph). As evidenced by Gagliardi, Rhodopsin is expressed by rod photoreceptors and not cone photoreceptors.
As evidenced by Eldred et al. cone photoreceptors in the human retina enable color vision, the three subtypes of human cones are defined by the visual pigment they express: blue-opsin (short wavelength, S), green-opsin (medium weave length, M) and red-opsin (long wavelength, L) (Introduction on page 1). THRB is required to induce red/green (L/M) opsin cones (see page 1, middle column).
The claim has been amended to recite the steps used to prepare the claimed cells. The claims are directed to a product. The claimed selection steps are a product by process limitation which does not distinguish the claimed cells from naturally occurring red/green cone photoreceptors.
The nature based product lacks markedly different characteristics (and thus is a product of nature exception) because: When the claimed cells are compared to their counterpart they does not have markedly different characteristics. The instant specification does not disclose any difference between the claimed cells and naturally cone photoreceptors with red and green opsins.
Prong Two: Does the claim recite additional elements that integrate the judicial exception into a practical application? No. The claims are directed to a product (i.e. a composition) and not a method of administration to a subject.
Question 2B: Do the claims recite any additional elements that amount to significantly more than the judicial exception?
Are there any additional elements recited in the claim beyond the exception identified above?
Yes.
(b) Do the additional elements, taken individually and as a combination result in significantly more?
Regarding claim 1: The claim recites the cells are “purified”. Purification does not distinguish the claimed cells from their naturally occurring counterpart (an embryonic retina cell). The claim recites the composition comprises at least 100,000 cells, wherein at least 75% of the total cells in the composition have the claimed characteristics. The number of cells does not make them markedly different than naturally occurring cone photoreceptors with red/green opsins.
Regarding claims 2-3: The claims are directed to the source of the cells. As set forth above, the claimed cells are isolated from embryonic retinas. Therefore the claims do not recite something significantly more than the recited judicial.
Regarding claims 6-9: The claims are directed to the number of cells with the claimed marker characteristics. These limitations do not result in something significantly different than a naturally occurring embryonic retinas with the claimed characteristics.
Therefore, claims 1-3 and 6-9 are not eligible subject matter under 35 USC 101.
APPLICANT’S ARGUMENTS
The arguments made in the response filed on 22 June 2026 are acknowledged. The Applicant argues purified cells are not naturally occurring.
Argument 1: The Applicant argues the claim requires a two-stage enrichment process comprising a closed-loop microfluidic/FACS-type sorting,
Response: The claims are directed to a product, and not a method of making the product. This does not distinguish the claimed cells from naturally occurring cone photoreceptors which express red and green opsins.
Argument 2: The Applicant argues the claimed composition requires at least 100,000 cells, wherein the cells constitute at least 75% of the composition. The Applicant argues cell number and purity are markedly different.
Response: The judicial exception is the claimed cells. The rejection above determines whether cells with the claimed characteristics are markedly different from their naturally occurring counterpart: cone photoreceptors which express red and green opsins. The number of cells does not distinguish the claimed cells from naturally occurring, human, cone photoreceptors which express red and green opsins. The Applicant has not provided evidence the claimed cells are markedly differently than their naturally occurring counterpart. The argument is not persuasive.
Argument 3: The Applicant argues the claimed composition is a pure population of cones. In contrast, cone photoreceptors exist with rods in a natural tissue.
Response: The analysis compares the claimed cells to a naturally occurring cone photoreceptors. Isolation does not make the cell markedly different. The Applicant has not provided evidence demonstrating the claimed cells are markedly different.
Argument 4: The Applicant argues the cels can be used for transplantation which cannot be performed using unmodified tissue.
Response: The arguments are directed to an intended use. The claims are directed to a product. The intended use does not result in a markedly different cellular characteristic.
Claim Rejections - 35 USC § 103
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claims 1-3 and 6-9 are rejected under 35 U.S.C. 103 as being unpatentable over Gagliardi et al. (Characterization and Transplantation of CD73-Positive Photoreceptors Isolated from Human iPSC-Derived Retinal Organoids
Stem Cell Reports, 2018; 11, 665-680) in view of Okunuki et al. (previously cited; Microglia inhibit photoreceptor cell death and regulate immune cell infiltration in response to retinal detachment. Proc Natl Acad Sci USA. 2018 Jul 3;115(27):E6264-E6273) and Basu et al. (previously cited; Purification of Specific Cell Population by Fluorescence Activated Cell Sorting (FACS). July 2010 41 pages 1-4) as evidenced by Eldred et al. (Thyroid hormone signaling specifies cone subtypes in human retinal organoids. Science 362,eaau 6348 (2018).
Gagliardi teaches isolates human cone photoreceptors (a composition) from rod photoreceptors (Figure 1D). The composition comprises long and medium length waves (red/green opsins; see red cone in 6D and red line in 6B OPN1LW/MW). The art teaches Red/green cones express OPN1W/M (red/green opsin) (page 671, left column, second paragraph). Gagliardi teaches photoreceptors express CD73+ (see page 666, left column, second paragraph). The art teaches cones express cone arrestin (see page 666, right column, seventh line from the bottom). As evidenced by Gagliardi, Rhodopsin is expressed by rod photoreceptors and not cone photoreceptors.
Figure 3A teaches a cell fraction which is CD73+ and OPN1LW/MW positive (Figure 3A).
The art teaches cell sorting is an effective strategy to separate a safe population of transplantable photoreceptors. (Abstract). It is noted Gagliardi teaches 300,000 sorted cells can be transplanted (see page 671, left column, second paragraph; see page 677, right column “Cell Transplantation” section).
The deficiencies are:
The art is silent regarding THRB expression.
The art is silent regarding the presence of CD11b+ cells.
As evidenced by Eldred et al. cone photoreceptors in the human retina enable color vision, the three subtypes of human cones are defined by the visual pigment they express: blue-opsin (short wavelength, S), green-opsin (medium weave length, M) and red-opsin (long wavelength, L) (Introduction on page 1). THRB is required to induce red/green (L/M) opsin cones (see page 1, middle column) and is required to induce L/M cone fate (page 1, middle paragraph). Therefore the red/green cones taught by Gagliardi would inherently expression THRB.
Okunuki teaches CD11b is a commonly used marker for identifying microglia, monocytes and macrophages E6265, left column, second paragraph). The art teaches microglia are present in retina (page E6268, left column, first paragraph). Staining with CD11b antibody can be used to identify cells that express CD11b (see text of Figure 6).
Basu teaches experimental and clinical studies often require highly purified cell populations. FACS is a technique of choice to purify cell populations of known phenotype. FACS is the preferred method when very high purity of the desired population is required (first paragraph of Abstract). Sorting parameters can be adjusted depending on the requirement of purity and yield (same cited section). Basu teaches the use of gating tools to define the populations of interest (see section 13 on page 2). Basu teaches FACS can be used to isolate cells that express multiple markers (see page 2, last paragraph). Basu teaches FACS is a highly sophisticated technique for purifying cell populations of interest, in which a very high purity (95-100%) of the sorted population can be obtained (first sentence of discussion).
It would have been obvious to prepare a composition comprising a population of CD11b- cells. Gagliardi teaches a population of cone photoreceptors which express CD73, cone arrestin, red/green opsin and THRB. The skilled artisan would only include CD11b- cells since Okunuki teaches CD11b is a marker for retinal microglia, monocytes and macrophages. One of ordinary skill would select cells that are CD11b- to exclude cells which are not photoreceptors. One would have had a reasonable expectation of success since Gagliardi uses cell sorting to isolate specific fractions of cells. One would have expected similar results since the references are each directed to identifying retinal cells.
It would have been obvious to isolate a population comprising at least 75% cells with the claimed characteristics. Gagliardi uses cell sorting to purify cells. Basu teaches cell sorting can be used to obtain a very high purity of 95-100%. Basu teaches sorting parameters can be adjusted depending on the requirement of purity and yield. The skilled artisan would therefore optimize these parameters to obtain a population that contains at least 75% of cells with the claimed markers. Because the claimed population is rendered obvious, it can be used for producing progenitor photoreceptor cells. Therefore claim 1 is rendered obvious.
Gagliardi teaches iPSC-derived retinal organoids (Abstract). Therefore claim 2 is included in this rejection. Claim3 is a product by process limitation which does not distinguish the claimed cells from those taught by Gagliardi. Claim 3 is included in this rejection.
It would have been obvious to combine the teachings of the prior art by optimizing the number of purified cells. Gagliardi uses cell sorting to isolate a desired cell type. Basu teaches cell sorting can be used to obtain a very high purity of 95-100%. Basu teaches sorting parameters can be adjusted depending on the requirement of purity and yield (same cited section). The skilled artisan would therefore optimize these parameters to obtain a purity of 95-100% for cells with the claimed characteristics. Therefore claims 6-9 are included in this rejection.
Therefore Applicant’s Invention is rendered obvious as claimed.
APPLICANT’S ARGUMENTS
The arguments made in the response filed on 22 June 2026 are acknowledged. New grounds of rejection have been set forth above.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE MOSS whose telephone number is (571) 270-7439. The examiner can normally be reached on Monday-Friday, 8am-5pm EST.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached on (571) 272-0614. The fax phone number for the organization where this application or proceeding is assigned is (571) 270-8439.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
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