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 ACTION
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 June 25, 2026 has been entered.
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
3. Applicant’s amendment filed May 22, 2026 and June 25,2 026 is acknowledged. Claims 2-3, 5, 7-10, 12-13 and 15 are canceled. Claims 1, 6 and 11 are amended. Claims 1, 4, 6, 11 and 14 are pending in this application. Election was made without traverse in the reply filed on August 2, 2023.
4. Claims 1, 4, 6, 11 and 14 are under examination in this office action.
5. Applicant’s arguments filed on May 22, 2026 and June 25,2 026 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Claim Rejections/Objections Withdrawn
6. The rejection of 5, 9-10 and 15 under 35 U.S.C. 102(a)(1) as being anticipated by Cheung (US10106773) is moot because the claims are canceled.
The rejection of 5, 9-10 and 15 under 35 U.S.C. 103 as being unpatentable over Cheung (US10106773) in view of Greiner et al. (Eur. Cells and Materials, 2011; 22:403-419) is moot because the claims are canceled.
The rejection of claims 5, 10 and 15 under 35 U.S.C. 103 as being unpatentable over Cheung (US10106773) in view of Greiner et al. (2011), and Ng et al. (SM Opthalmol. J. 2015; 1:1003) is moot because the claims are canceled.
Claim Rejections/Objections Maintained
In view of the amendment filed on May 22, 2026 and June 25,2 026, the following rejections are maintained.
Claim Rejections - 35 USC § 102
7. 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 1, 4, 6, 11 and 14 stand rejected under 35 U.S.C. 102(a)(1) as being anticipated by Cheung (US10106773). The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 1, 4, 6, 11 and 14 as amended are drawn to methods of treating a retinal degeneration, comprising administering to a subject in need thereof, by subretinal or intravitreal injection, human neural crest-derived nasal inferior turbinate stem cells (hITSCs) or a cellular therapeutic agent or a quasi-drug composition comprising the claimed hITSCs, wherein the hITSCs are subcultured while retaining self-renewal capacity and multi-differentiation activity and possess the differentiation capacity to develop into rod photoreceptor cells among photoreceptors on the degenerated retina.
Briefly, Cheung (US10106773) teaches a method of treating a retinal degenerative disease, comprising administering including intravitreally administering (see col.15, lines 24-63) to a subject in need thereof a composition comprising adherent human adult stem cells isolated from neural crest derived tissue nasal turbinate (see col. 7, lines 49-61; col. 8, lines 24-26; col.8, lines 28-33; col.8, line 45-col.9, line 30), which are adherent human neural crest-derived nasal turbinate stem cells isolated from human nasal turbinate which includes inferior turbinate and include the claimed adherent human neural crest-derived nasal inferior turbinate; wherein the retinal degenerative disease includes retinitis pigmentosa, age-related macular degeneration, glaucoma (See col.7, lines 30-col. 8, lines 60; col. 15, lines 22-23; 34-45; col. 25-31, Example 4), and wherein the adherent human neural crest-derived nasal turbinate stem cells express connexin 43, stem cell markers including Oct4, Nanog, Sox2, Klf4 or combination thereof and neural crest markers including p75 neurotrophin receptor, Nestin, Sox10, N-cadherin, Notch1, BMP2, Slug, Snail or combination thereof (see col. 8, lines 45-col. 9, lines 6), and are capable of differentiating into rod photoreceptors expressing rhodopsin as recited in claims 1, 4, 6, 11 and 14 (see col. 6, lines 36-37) Thus, claims 1, 4, 6, 11 and 14 are anticipated by Cheung (US10106773).
Response to Arguments
On p. 4 of the response, Applicant argues that Cheung does not anticipate pending claims because Cheung does not teach each and every element of each of pending claims and Cheung does not teach subretinal injection.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2131, Cheung does anticipate instant claims because:
i. instant claims encompass treating a retinal degeneration by subretinal or intravitreal administering to a subject in need thereof adherent human neural crest-derived nasal inferior turbinate stem cells.
ii. The new limitation "intravitreal" injection recited in proposed claims is taught by Cheung (see col.15, lines 24-63).
Cheung does teach intravitreally administering (see col.15, lines 24-63) to a subject with a retinal degenerative disease a composition comprising adherent human adult stem cells isolated from neural crest derived tissue nasal turbinate which includes inferior turbinate and the claimed adherent human neural crest-derived nasal inferior turbinate stem cells (see col. 7, lines 49-61; col. 8, lines 24-26; col.8, lines 28-33; col.8, line 45-col.9, line 30), and wherein the retinal degenerative disease includes retinitis pigmentosa, age-related macular degeneration, glaucoma (See col.7, lines 30-col. 8, lines 60; col. 15, lines 22-23; 34-45; col. 25-31, Example 4).
iii. The limitation “wherein the stem cells are subcultured while retaining self-renewal capacity and multi-differentiation ability and possesses the differentiation capacity to develop into rod photoreceptor cells among photoreceptor cells on the degenerated retina upon administration” are inherent features and characteristics of adherent human neural crest-derived nasal inferior turbinate stem cells, which are taught by Cheung (US10106773).
The adherent human neural crest-derived nasal turbinate stem cells disclosed by Cheung express connexin 43, stem cell markers including Oct4, Nanog, Sox2, Klf4 or combination thereof and neural crest markers including p75 neurotrophin receptor, Nestin, Sox10, N-cadherin, Notch1, BMP2, Slug, Snail or combination thereof (see col. 8, lines 45-col. 9, lines 6), and are capable of differentiating into rod photoreceptors expressing rhodopsin as recited in claims 1, 4, 6, 11 and 14 (see col. 6, lines 36-37). The adherent human neural crest-derived nasal turbinate stem cells disclosed by Cheung express markers of the adherent human neural crest-derived nasal inferior turbinate stem cells (hITSCs) disclosed by Greiner (see p.6, 1st col. figure 2; see the details under the 103 rejection below) and thus are capable of differentiating into rod photoreceptors expressing rhodopsin as recited in claims 1, 4, 6, 11 and 14 upon administration.
Thus, claims 1, 4, 6, 11 and 14 are anticipated by Cheung. Accordingly, the rejection of claims 1, 4, 6, 11 and 14 under 35 U.S.C. 102(a)(1) as being anticipated by Cheung (US10106773) is maintained.
Claim Rejections - 35 USC § 103
8. 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 1, 4, 6, 11 and 14 stand rejected under 35 U.S.C. 103 as being unpatentable over Cheung (US10106773) in view of Greiner et al. (Eur. Cells and Materials, 2011; 22:403-419. DOI:10.22203/eCM.v022a30). The rejection is maintained for the reasons of record and the reasons set forth below.
Response to Arguments
On p. 5 of the response, Applicant argues that Cheung does not anticipate pending claims because Cheung and Greiner do not teach subretinal injection. Applicant further cites In re Vaeck in support of the arguments.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2141, MPEP2141-I, rationales identified by the Court in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007)), MPEP2141-II, the basic factual inquires of Graham v. John Deere Co.(Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966)),and MPEP §2141.01-2147.03, the cited references do render the claimed invention obvious because:
i. For the reasons set forth above, Cheung does teach intravitreal injection and the method of claims 1, 4, 6, 11 and 14.
ii. Even if Cheung does not explicitly teach the adherent human neural crest-derived nasal turbinate stem cells are only isolated from the human nasal inferior turbinate, Greiner teaches that culturing adherent human neural crest-derived nasal inferior turbinate stem cells (hITSCs) and subculturing adherent hITSCs is an efficient way to obtain adherent hITSCs and for their use for treatment of neurodegenerative diseases (see p.403, abstract; p. 404, 2nd col. section: cultivation of ITSCs using human blood plasma derived 3D matrix to p. 405, 1st col., 1st paragraph; p. 408-409, figure 3). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known adherent hITSCs isolated from a human adult inferior turbinate and the known technique of culturing and isolating hITSCs disclosed by Greiner to the Cheung’s method and yield the predictable result of treating a retinal degenerative disease including retinitis pigmentosa, age-related macular degeneration, glaucoma because isolating and culturing adherent hITSCs from the human nasal inferior turbinate is efficient, and adherent hITSCs have been successfully used for treatment of neurodegenerative diseases including retinal degenerative diseases using stem cell therapy.
The method of Cheung and Greiner uses the same material (i.e. adherent human neural crest-derived nasal inferior turbinate stem cells), the same active step (i.e. intravitreally administering) in the same patient population (i.e. retinal degenerative disease) as instantly claimed. Thus, upon intravitreal administration, the adherent human neural crest-derived nasal inferior turbinate stem cells disclosed by Cheung and Greiner can differentiate into rod photoreceptors expressing rhodopsin in the retinal environment as instantly claimed because the material, the active step and the patient population are identical to the instant claims.
Accordingly, the rejection of claims 1, 4, 6, 11 and 14 under 35 U.S.C. 103 as being unpatentable over Cheung (US10106773) in view of Greiner is maintained.
Claim Rejections - 35 USC § 103
9. Claims 1, 4, 6, 11 and 14 are rejected under 35 U.S.C. 103 as being unpatentable over Cheung (US10106773) in view of Greiner et al. (2011) as applied to claims 1, 4, 6, 11 and 14 above, and further in view of Ng et al. (SM Opthalmol. J. 2015; 1:1003). The rejection is maintained for the reasons of record and the reasons set forth below.
Response to Arguments
On p. 5-11 of the response, Applicant argues that i) Cheung does not teach administration of nasal inferior turbinate stem cells that develop into rod photoreceptor cells upon administration because: 1) Cheung is directed to in vitro differentiation, which is ex vivo differentiation induction, not in vivo differentiation; 2) the claimed method does not require a separate differentiation process and the inferior turbinate stem cells spontaneously induced by the subretinal/intravitreal microenvironment to differentiate into rod photoreceptor cells in an animal model; 3) Cheung does not teach the claimed nasal inferior turbinate stem cells because Cheung is directed to periodontal ligament-derived cells while listing various neural crest-derived tissue including nasal turbinate; ii) Grener is directed to obtaining and culturing human neural crest-derived nasal inferior turbinate stem cells but Grener does not teach treatment of retinal degeneration or in vivo rod photoreceptor differentiation after administration; iii) Ng is directed to treatment of retinal degenerative diseases by intravitreal or subretinal administration of mesenchymal stem cells, which are not the claimed human neural crest-derived nasal inferior turbinate stem cells; iv) there is no motivation to combine or modify the cited references because: 1) Cheung’s experiments are based on PDL-derived cells and differentiation ex vivo; 2) Geiner is based on in vitro culture and expansion of inferior turbinate-derived stem cells; 3) upon administration, the claimed stem cells possess the capacity to develop into rod photoreceptor cells without prior differentiation induction; 4) Ng is directed to MSC not the claimed neural crest-derived nasal inferior turbinate stem cells; 5) the rejection is based on hindsight of the claimed invention; iv) the claimed results of in vivo rod photoreceptor differentiation from administered inferior turbinate stem cells are not predictable because 1) in vitro experiments cannot predict in vivo results; 2) different stem cells behave differently in the retinal environment; 3) the claimed invention shows unexpected in vivo therapeutic results in an animal model.
Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2141, MPEP2141-I, rationales identified by the Court in KSR (KSR International Co. v. Teleflex Inc. (KSR), 550 U.S. 398, 82 USPQ2d 1385 (2007)), MPEP2141-II, the basic factual inquires of Graham v. John Deere Co.(Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966)),and MPEP §2141.01-2147.03, the cited references do render the claimed invention obvious because:
i. For the reasons set forth above under the 102 rejection, Cheung does teach intravitreally administering (see col.15, lines 24-63) a composition comprising adherent human adult stem cells isolated from neural crest derived tissue nasal turbinate (see col. 7, lines 49-61; col. 8, lines 24-26; col.8, lines 28-33; col.8, line 45-col.9, line 30) to a subject with a retinal degenerative disease including retinitis pigmentosa, age-related macular degeneration, glaucoma (See col.7, lines 30-col. 8, lines 60; col. 15, lines 22-23; 34-45; col. 25-31, Example 4).
The adherent human neural crest-derived nasal turbinate stem cells disclosed by Cheung express connexin 43, stem cell markers including Oct4, Nanog, Sox2, Klf4 or combination thereof and neural crest markers including p75 neurotrophin receptor, Nestin, Sox10, N-cadherin, Notch1, BMP2, Slug, Snail or combination thereof (see col. 8, lines 45-col. 9, lines 6), and are capable of differentiating into rod photoreceptors expressing rhodopsin as recited in claims 1, 4, 6, 11 and 14 (see col. 6, lines 36-37).
Cheung teaches a method of using the same material (i.e. adherent human neural crest-derived nasal turbinate stem cells), the same active step (i.e. intravitreally administering) in the same patient population (i.e. retinal degenerative disease) as instantly claimed. Thus, upon intravitreal administration, the adherent human neural crest-derived nasal turbinate stem cells disclosed by Cheung can differentiate into rod photoreceptors expressing rhodopsin in the retinal environment as instantly claimed because the material, the active step and the patient population are identical to the instant claims.
ii. For the reasons set forth above under the 103 rejection, Cheung and Greiner do teach intravitreally administering a composition comprising adherent human neural crest-derived nasal inferior turbinate stem cells (hITSCs) to a subject with a retinal degenerative disease including retinitis pigmentosa, age-related macular degeneration, glaucoma.
Applicant cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In this case, even if Cheung does not explicitly teach the adherent human neural crest-derived nasal turbinate stem cells are only isolated from the human nasal inferior turbinate, Greiner teaches this limitation and provides motivation and an expectation of success because Greiner teaches that culturing adherent human neural crest-derived nasal inferior turbinate stem cells (hITSCs) and subculturing adherent hITSCs is an efficient way to obtain adherent hITSCs and for their use for treatment of neurodegenerative diseases (see p.403, abstract; p. 404, 2nd col. section: cultivation of ITSCs using human blood plasma derived 3D matrix to p. 405, 1st col., 1st paragraph; p. 408-409, figure 3). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known adherent hITSCs isolated from a human adult inferior turbinate and the known technique of culturing and isolating hITSCs disclosed by Greiner to the Cheung’s method and yield the predictable result of treating a retinal degenerative disease including retinitis pigmentosa, age-related macular degeneration, glaucoma because isolating adherent hITSCs from the human nasal inferior turbinate is efficient, and adherent hITSCs can be used for treatment of neurodegenerative diseases including retinal degenerative diseases using stem cell therapy because Greiner teaches that culturing adherent human neural crest-derived nasal inferior turbinate stem cells (hITSCs) and subculturing adherent hITSCs is an efficient way to obtain adherent hITSCs for treatment of neurodegenerative diseases including retinal degenerative diseases.
The method of Cheung and Greiner uses the same material (i.e. adherent human neural crest-derived nasal inferior turbinate stem cells), the same active step (i.e. intravitreally administering) in the same patient population (i.e. retinal degenerative disease) as instantly claimed. Thus, upon intravitreal administration, the adherent human neural crest-derived nasal inferior turbinate stem cells disclosed by Cheung and Greiner can differentiate into rod photoreceptors expressing rhodopsin in the retinal environment as instantly claimed because the material, the active step and the patient population are identical to the instant claims.
iii. In response to applicant’s argument that there is no teaching, suggestion, or motivation to combine the references, the examiner recognizes that obviousness may be established by combining or modifying the teachings of the prior art to produce the claimed invention where there is some teaching, suggestion, or motivation to do so found either in the references themselves or in the knowledge generally available to one of ordinary skill in the art. See In re Fine, 837 F.2d 1071, 5 USPQ2d 1596 (Fed. Cir. 1988), In re Jones, 958 F.2d 347, 21 USPQ2d 1941 (Fed. Cir. 1992), and KSR International Co. v. Teleflex, Inc., 550 U.S. 398, 82 USPQ2d 1385 (2007).
It is not necessary that the claimed invention be expressly suggested in any one or all of the references to justify combining their teachings; rather the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981). The motivation to combine can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. MPEP. §2144.07. Specific statements in the references themselves which would spell out the claimed invention are not necessary to show obviousness, since questions of obviousness involve not only what references expressly teach, but what they would collectively suggest to one of ordinary skill in the art. See CTS Corp. v. Electro Materials Corp. of America 202 USPQ 22 (DC SNY 1979); and In re Burckel 201 USPQ 67 (CCPA 1979).
Further, in considering the disclosure of a reference, it is proper to take into account not only specific teaching of the reference but also the inferences which one skilled in the art would reasonably be expected to draw therefrom. In re Preda, 401 F.2d 825, 159 USPQ 342, 344 (CCPA 1968).
Moreover, Applicant cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
In this case, Cheung and Greiner teach the claimed method of claims 1, 4, 6, 11 and 14 for the reasons set forth above. While Cheung and Greiner do not teach subretinal injection as recited in claims 1, 6 and 11, Ng teaches this limitation and provides motivation and an expectation of success in using subretinal injection in the method of Cheung and Greiner because intravitreal or subretinal administration of different stem cells including neural crest-derived stem cells (NCSCs) or mesenchymal stem cells (MSCs) have been used for treatment of different retinal degenerative diseases and the MSCs can differentiate into rod photoreceptors expressing rhodopsin.
In particular, Ng teaches treating a retinal degenerative disease including retinitis pigmentosa, age-related macular degeneration, glaucoma (See p.2, col. 1, section: Current Progress of Mesenchymal Stem cells in Ocular Research to p. 3, col.2; p. 3, col.2, section: Human Clinical Trials using Stem cell in Ophthalmology to p. 6, tables 2-5) by intravitreal or subretinal administering (see p. 2, col.2, paragraph 2; p. 3, col.2, section: Human Clinical Trials using Stem cell in Ophthalmology to p. 6, tables 2-5) to a subject in need thereof a composition comprising different stem cells including neural crest-derived stem cells (NCSCs) or mesenchymal stem cells (MSCs) and wherein the MSCs differentiate into rod photoreceptors expressing rhodopsin as recited in claims 1, 4, 6, 11 and 14 (p. 3, col.2, section: Human Clinical Trials using Stem cell in Ophthalmology). Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known intravitreal or subretinal injection method and the known technique disclosed by Ng to the method of Cheung and Greiner, and yield the predictable result of treating a retinal degenerative disease including retinitis pigmentosa, age-related macular degeneration, glaucoma because intravitreal or subretinal injection of neural-crest stem cells or hITSCs has been successfully used for treatment of retinal degenerative diseases including retinitis pigmentosa, age-related macular degeneration, glaucoma.
iv. In response to Applicant’s arguments related to unexpected results, the Examiner’s asserts that the claimed method is NOT unexpected because:
a) Cheung teaches a method of using the same material (i.e. adherent human neural crest-derived nasal turbinate stem cells), the same active step (i.e. intravitreally administering) in the same patient population (i.e. retinal degenerative disease). Thus, upon intravitreal administration, the adherent human neural crest-derived nasal turbinate stem cells disclosed by Cheung can differentiate into rod photoreceptors expressing rhodopsin in the retinal environment as instantly claimed because the material, the active step and the patient population are identical to the instant claims.
b) Even if Cheung does not explicitly teach the adherent human neural crest-derived nasal turbinate stem cells are only isolated from the human nasal inferior turbinate, Greiner teaches that culturing adherent human neural crest-derived nasal inferior turbinate stem cells (hITSCs) and subculturing adherent hITSCs is an efficient way to obtain adherent hITSCs and for their use for treatment of neurodegenerative diseases. The method of Cheung and Greiner uses the same material (i.e. adherent human neural crest-derived nasal inferior turbinate stem cells), the same active step (i.e. intravitreally administering) in the same patient population (i.e. retinal degenerative disease) as instantly claimed. Thus, upon intravitreal administration, the adherent human neural crest-derived nasal inferior turbinate stem cells disclosed by Cheung and Greiner can differentiate into rod photoreceptors expressing rhodopsin in the retinal environment as instantly claimed because the material, the active step and the patient population are identical to the instant claims.
c) While Cheung and Greiner do not teach subretinal injection as in independent claims 1, 6 and 11, Ng teaches intravitreal or subretinal administration (see p. 2, col.2, paragraph 2; p. 3, col.2, section: Human Clinical Trials using Stem cell in Ophthalmology to p. 6, tables 2-5) of stem cells including neural crest-derived stem cells (NCSCs), mesenchymal stem cells (MSCs) can result in differentiation into rod photoreceptors expressing rhodopsin (p. 3, col.2, section: Human Clinical Trials using Stem cell in Ophthalmology) and thereby treating a retinal degenerative disease including retinitis pigmentosa, age-related macular degeneration, glaucoma (See p.2, col. 1, section: Current Progress of Mesenchymal Stem cells in Ocular Research to p. 3, col.2; p. 3, col.2, section: Human Clinical Trials using Stem cell in Ophthalmology to p. 6, tables 2-5).
The method of Cheung, Greiner and Ng uses the same material (i.e. adherent human neural crest-derived nasal inferior turbinate stem cells), the same active step (i.e. intravitreally or subretinally administering) in the same patient population (i.e. retinal degenerative disease) as instantly claimed. Thus, upon intravitreal or subretinal administration, the adherent human neural crest-derived nasal inferior turbinate stem cells disclosed by Cheung, Greiner and Ng can differentiate into rod photoreceptors expressing rhodopsin in the retinal environment as instantly claimed because the material, the active step (intravitreal or subretinal injection) and the patient population are identical to the instant claims and Cheung, Greiner and Ng teaches that intravitreal or subretinal administration of adherent human neural crest-derived nasal inferior turbinate stem cells can differentiate into rod photoreceptors expressing rhodopsin in the same retinal environment.
Further, evidence of unexpected results must be weighed against evidence supporting prima facie obviousness in making a final determination of the obviousness of the claimed invention. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978). See MPEP 716.02(c)-I. Any differences between the claimed invention and the prior art may be expected to result in some differences in properties. The issue is whether the properties differ to such an extent that the difference is really unexpected. See: MPEP §716.02. In addition, “A greater than expected result is an evidentiary factor pertinent to the legal conclusion of obviousness ... of the claims at issue.” In re Corkill, 711 F.2d 1496, 226 USPQ 1005 (Fed. Cir. 1985). See MPEP 716.02(a)-I. Moreover, evidence of unexpected results is frequently in the form of a direct comparison of the claimed invention with the closest prior art which is commensurate in scope with the claims. See: e.g., In re Boesch, 617 F.2d 272, 205 USPQ 215 (CCPA 1980).
In this case, Applicants fails to provide evidence of side-by-side comparisons between the claimed method versus the method of the cited references to demonstrate unexpected results as claimed. “Evidence of unexpected results must be weighed against evidence supporting prima facie obviousness in making a final determination of the obviousness of the claimed invention. In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978).” See MPEP 716.02(c)-I. Since Applicant fails to provide any evidence as discussed above to support any unexpected results as claimed, the claimed methods are obvious over the prior art, absent evidence to the contrary.
Accordingly, the rejection of claims 1, 4, 6, 11 and 14 under 35 U.S.C. 103 as being unpatentable over Cheung (US10106773) in view of Greiner et al. (2011) as applied to claims 1, 4, 6, 11 and 14 above, and further in view of Ng et al. (2015) is maintained.
Conclusion
10. NO CLAIM IS ALLOWED.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
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Chang-Yu Wang
July 25, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
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