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 .
DETAILED OFFICE ACTION
This Office Action is in response to the papers filed on 26 August 2025.
CLAIMS UNDER EXAMINATION
Claims 1-3 and 6-9 have been examined on their merits.
PRIORITY
Provisional Application 62/819,160, 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.
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 claims that set forth a nature based product is: a population of cells that is CD73+, Thrb+ and CD1b-. As evidenced by the instant specification, the claimed cells are derived from embryonic retinas (see page 2, lines 1-5). Cone receptor progenitor cells (CPCs) are dissociated from embryonic retinas and sorted based on the presence of CD74 and Thrb and absence of CD11b (see page 18, lines 7-14). Therefore the closest naturally occurring counterparts are embryonic retina receptors. Claim 1 has been amended to recite the ells are for producing progenitor photoreceptor cells. This is an intended use that does not distinguish the claimed cells from their naturally occurring counterparts. The claim recites the cells with the claimed markers comprise at least 75% of the cell count. The number of cells in the composition does not distinguish the cells from those present in retina.
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 occurring cells found in embryonic retinas.
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).
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 28 October 2025 are acknowledged. The Applicant argues purified cells are not naturally occurring. The Applicant argues the purified population can only occur through highly complex technological processing and techniques. The Applicant argues cells found in naturally occurring retinas are not purified, and “no naturally occurring compositions of cells found in embryonic retinas would be present in a concentration where 75% of the cells exhibit he claimed markers”. The Applicant argues the cells cell population capable of use for treating ocular disorders.
EXAMINER’S RESPONSE
The arguments are not persuasive As evidenced by the instant specification, the claimed cells are dissociated from a naturally occurring retina. Isolation of the cell from the retina of an animal does not result in a markedly different cell. While the Applicant argues the purification requires “highly complex technological processing and techniques”, the claim is not drawn to a method of obtaining the product. The specification does not disclose isolation of the cell results in a markedly different cell. The amended claim recites the composition is for producing progenitor photoreceptor cells. The claim is not directed to a method of using the cells to produce photoreceptor cells. The number of naturally occurring cells in the composition does not result in a markedly different characteristic. Therefore the arguments are not persuasive.
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 Koso et al. (CD73, a Novel Cell Surface Antigen That Characterizes Retinal Photoreceptor Precursor Cells. Investigative Ophthalmology & Visual Science November 2009, Vol.50, 5411-5418) in view of Ng et al. (Two Transcription Factors Can Direct Three Photoreceptor Outcomes from Rod Precursor Cells in Mouse Retinal Development. The Journal of Neuroscience, August 3, 2011 31(31):11118–11125), Okunuki et al. (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. (Purification of Specific Cell Population by Fluorescence Activated Cell Sorting (FACS). July 2010 41 pages 1-4).
Koso identifies cell surface markers of photoreceptors and its precursors cells (see page 5411 “Purpose”). The art teaches CD73 is an early photoreceptor lineage marker (see page 5411 “Results”). Neural retinas are isolated and stained with anti-CD73 antibodies. Cells are sorted using fluorescence activated cell sorting (FACS) (last paragraph of page 5411-5412). CD73 expression is detected in cells derived from an E16 mouse (see first paragraph of Results, “Characterization of CD73+ Cells in the Developing Retina).
Cells are purified in a cell sorter (page 5413, right column, last paragraph; see Figure 2). The art teaches a purity of 90% is obtained (see text of Figure 2). Koso teaches expression of the CD73 antigen increased dramatically with retinal development (see first paragraph of “Results” on page 5412). Koso teaches CD73 expression is conserved in primate rod cells, and CD73 provides a useful tool to purify photoreceptor cells for transplantation aimed at the regeneration of photoreceptors (Conclusions section on page 5411). Koso teaches “we show that the purification of CD73 is an efficient way to achieve photoreceptor cell generation by transplantation” (see page 5416, right column, last paragraph).
Koso sorts cells to obtain photoreceptor cells. CD73+ precursor cells are isolated. The art is silent regarding expression of Thrb and CD11b.
Ng teaches the visual capability of a species depends upon the generation of
distinct photoreceptor types. Mammals possess three photoreceptor types: rods for dim light vision and two cone types for bright light vision (first paragraph of introduction).
Ng teaches transcription factors play critical roles throughout the course of photoreceptor differentiation from multipotent progenitor cell to postmitotic precursor to terminally differentiated neuron. Ng teaches thyroid hormone receptor 2 (TRβ2), one of the receptor isoforms encoded by Thrb, profoundly influences photoreceptor fates (page 11118, right column, second paragraph). The art identifies TRβ2-positive cells in the retina (see page 11121, right column, second paragraph). Ng identifies precursors in retina that express TRβ2 in the late embryonic state (see page 11123, left column, last paragraph; Figure 6).
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). The success of staining and thereby sorting depends largely on the selection of the identifying markers and the choice of mAb. 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 controls (FMO) can be used to distinguish negative populations, and to determine where to place gates for experimental cells (sane cited section). Basu teaches FACS can be used to isolate cells that express multiple markers (see page 2, last paragraph; B cells (B220+TCRβ-) and CD4 T cells (CD4+TCRβ+). 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 combine the teachings of the prior art to purify a population of CD73+, Thrb+ CD11b- cells. Koso isolates CD73+ photoreceptor precursor cells in the retina. One would have been motivated to isolate cells that are also Thrb+ since Ng teaches photoreceptor precursors cells express thyroid hormone receptor 2 (TRβ2), one of the receptor isoforms encoded by Thrb. The skilled artisan would isolate cells that express both markers since the references teach each is present in precursor cells. It would have been obvious to isolate cells that do not express CD11b (hence, CD11b-) 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 retinal cells that are not photoreceptor precursors. One would have had a reasonable expectation of success isolating CD73+, Thrb+ CD11b- cells since Koso uses FACS to sort and isolate cells and Basu teaches FACS can be used to sort and isolate cells based on multiple cell surface makers. One would have expected similar results since Koso, Ng and Okunuki are each directed to identifying retinal cells.
It would have been obvious to isolate a population comprising at least 75% CD73+,Thrb+, CD11b- cells. Koso uses cell sorting and FACS to purify cells. Basu teaches FACS 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.
Koso teaches embryonic retina. Therefore claims 2-3 are included in this rejection.
It would have been obvious to combine the teachings of the prior art by optimizing the number of purified cells. Koso uses FACS, and isolates cells that are 90% CD73+. Basu teaches FACS 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 28 October 2025 are acknowledged. The Applicant argues no single reference teaches all of the markers. The Applicant argues there is no reason to combine the teachings of the prior art. The Applicant argues the possible combination of markers “could reach the millions”. The Applicant argues the cells in “Okunuki are CD11+ not CD11-“. Therefore the Applicant argues this reference teaches away from the claimed population. The Applicant argues the remaining references do not teach a composition with at least 75% CD73+, THrb+ and CD11b- cells.
EXAMINER’S RESPONSE
The arguments are not persuasive. Koso isolates cells from a retina. The art explicitly teaches retinal photoreceptors and its precursors cells are CD73+. Koso teaches CD73 provides a useful tool to purify photoreceptor cells for transplantation. Koso teaches “we show that the purification of CD73 is an efficient way to achieve photoreceptor cell generation by transplantation” (supra). Koso is silent regarding expression of Thrb and CD11b on these cells.
Ng teaches TRβ2, one of the receptor isoforms encoded by Thrb, profoundly influences photoreceptor fates. Ng uses identifies precursors in retina that express TRβ2 in the late embryonic state.
Okunuki teaches CD11b is a commonly used marker for identifying microglia, monocytes and macrophages in retina.
It would have been obvious to select cells that are CD73+ and Thrb+. One would have been motivated to do so since Koso and Ng teach both markers are present in photoreceptor precursor cells. The skilled artisan would select cells that do not express CD11b (hence, CD11b-) since Okunuki teaches this marker is present on microglia, monocytes and macrophages (hence, non-photoreceptor cells).
The Applicant argues Okunuki teaches cells that are “CD11+” and therefore teaches away from the claimed cells. In response: The rejection acknowledges Okunuki teaches cells that are CD11+, but these are not photoreceptor cells. Koso and Ng are directed to photoreceptor cells and their precursors present in the retina. Okunuki teaches CD11b expression is used to identify microglia, monocytes and macrophages (hence, cells that are not photoreceptors) in the retina. One would select cells that are also CD11b- to exclude microglia, monocytes and macrophages.
The arguments are not persuasive.
CONCLUSION
No Claims Are Allowed
THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any extension fee pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the date of this final action.
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) 273-8300.
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/NATALIE M MOSS/ Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653