174Notice 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
RESPONSE TO AMENDMENT
Status of Application/Amendments/claims
2. Applicant’s amendment filed March 24, 2025 is acknowledged. Claims 11-13 are cancelled. Claim 1 is amended. Claims 15-20 are newly added. Claims 1-10, 14 and newly added claims 15-20 are pending in this application and under examination in this office action.
3. Applicant’s arguments filed on March 24, 2025 have been fully considered but they are not deemed to be persuasive for the reasons set forth below.
Specification
4. The objection to the specification is withdrawn in response to Applicant’s amendment to the specification.
Claim Rejections/Objections Withdrawn
5. The rejection of claims 7-8 and 14 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite
The rejection of claims 11-13 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, lack of scope of enablement is moot because the claims are canceled.
The rejection of claims 11-13 under 35 U.S.C. 102(a)(1) & (a)(2) as being anticipated by Bopardikar et al. (US2017/0029770; issued as US11072776) as evidenced by Fan et al. (Cell Transplantation, 2015; 24:471-485) and Dezawa et al. (US2011/0070647) is moot because the claims are canceled.
The rejection of claims 11-13 under 35 U.S.C. 103 as being unpatentable over Bopardikar et al. (US2017/0029770; issued as US11072776) in view of Dezawa et al. (US2011/0070647) and evidentiary references: Fan et al. (2015), Kirton et al. (see abstract; Stroke, 2013; 44:3265-3271) and Camilo et al. (see abstract; Stroke, 2004; 35:1769-1775) is moot because the claims are canceled.
Claim Rejections/Objections Maintained
In view of the amendment filed on March 24, 2025, the following rejections are maintained.
Claim Rejections - 35 USC § 112
6. The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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 1-10 and 14-20 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 for ameliorating brain damage by the claimed cell preparation comprising pluripotent stem cells (PSCs) expressing SSEA-3 and CD105 and negative for markers recited in claims 3-5, does not reasonably provide enablement for a method of treating and curing a brain disorder associated with fetal growth retardation selected from abnormal quality of movement, abnormal neurological development and the fetal growth retardation results from chronic hypoxemia, circulatory insufficiency and malnutrition caused by placental and umbilical factors by the claimed cell preparation as broadly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. The specification does not enable the invention of claims 1-10 and 14-20 that is directed to a method of curing a brain disorder associated with fetal growth retardation including abnormal quality of movement, abnormal neurological development and the fetal growth retardation results from chronic hypoxemia, circulatory insufficiency and malnutrition caused by placental and umbilical factors. The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 1-10 and 14-20 as amended are drawn to a method for amelioration and/or treatment of a brain disorder associated with fetal growth retardation in a subject in need thereof, comprising administering to the subject a cell preparation comprising pluripotent stem cells (PSCs) positive for SSEA-3 isolated from mesenchymal tissue or cultured mesenchymal cells of a living organism, wherein the PSCs are CD105+, have low or non-existent telomerase activity, the ability to differentiate into any three germ layers, no neoplastic proliferation and self-renewal ability, wherein the brain disorder associated with fetal growth retardation is selected from the group consisting of abnormal quality of movement and abnormal neurological development, and the fetal growth retardation results from at least one of chronic hypoxemia, circulatory insufficiency and malnutrition caused by placental and umbilical factors.
Response to Arguments
On p. 13 of the response, Applicant argues that pending claims meet the enablement requirement.
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 §2164, MPEP §§2164.01-2164.06(b) & 2164.08, neither the specification nor the prior art provides sufficient guidance to enable a skilled artisan to practice the full scope of the claimed invention without undue experimentation because:
i. Based on paragraph [0053] of the published specification (US20200197446), the definition of “treatment” encompasses curing (i.e. completely eliminating brain disorders associated with fetal growth retardation). Thus, the instant claims encompass a method of curing a brain disorder associated with fetal growth retardation including abnormal quality of movement and abnormal neurological development, and the fatal growth retardation is caused by chronic hypoxemia, circulatory insufficiency or malnutrition caused by placental and umbilical factors or a combination thereof.
[0053] According to the invention, the cell preparation and pharmaceutical composition ..….The term "treatment" refers to suppressing or completely eliminating brain disorders associated with fetal growth retardation.
However, neither the specification nor the prior art provides sufficient guidance or evidence to demonstrate that administration of the claimed cell preparation to a subject suffering from a disorder associated with fetal growth retardation can cure a brain disorder associated with fetal growth retardation including abnormal quality of movement and abnormal neurological development, and the fatal growth retardation is caused by chronic hypoxemia, circulatory insufficiency or malnutrition caused by placental and umbilical factors or a combination thereof.
There is no cure for the claimed brain disorder associated with fetal growth retardation including abnormal quality of movement, abnormal neurological development by any given agent as evidenced by the factsheet of the brain disorder associated with fetal growth retardation (retrieved from the Cleveland Clinic website: my.clevelandclinic.org/health/diseases/24017-intrauterine-growth-restriction on 07/08/2025). Neither the specification nor the prior art provides sufficient guidance to enable a skilled artisan to practice the full scope of the claimed invention without undue experimentation as it pertains to treatment or curing or completely eliminating brain disorder associated with fetal growth retardation including abnormal quality of movement, abnormal neurological development caused by chronic hypoxemia, circulatory insufficiency or malnutrition caused by placental and umbilical factors or a combination thereof because there is no cure for brain disorders associated with fetal growth retardation.
Therefore, in view of the lack of guidance in the specification, the unpredictability of the inventions, the breadth of the claims, and the current status of the prior art, undue experimentation would be required of a skilled artisan to perform in order to practice the claimed invention as it pertains to treatment or curing or completely eliminating brain disorder associated with fetal growth retardation caused by chronic hypoxemia, circulatory insufficiency or malnutrition caused by placental and umbilical factors or a combination thereof by the claimed cell preparation as instantly claimed.
Accordingly, the rejection of claims 1-10 and 14-20 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, lack of scope of enablement is 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 1-6 and 9-10 are rejected under 35 U.S.C. 102(a)(1) & (a)(2) as being anticipated by Bopardikar et al. (US2017/0029770; issued as US11072776) as evidenced by Fan et al. (Cell Transplantation, 2015; 24:471-485) and Dezawa et al. (US2011/0070647). The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 1-6 and 9-10 as amended are drawn to a method for amelioration and/or treatment of a brain disorder associated with fetal growth retardation in a subject in need thereof, comprising administering to the subject a cell preparation comprising pluripotent stem cells positive for SSEA-3 (SSEA-3+-PSCs) isolated from mesenchymal tissue or cultured mesenchymal cells of a living organism, wherein the SSEA-3+-PSCs are CD105+ (SSEA-3+/CD105+-PSCs), have low or non-existent telomerase activity, the ability to differentiate into any three germ layers, no neoplastic proliferation and self-renewal ability; and wherein the brain disorder associated with fetal growth retardation is selected from the group consisting of abnormal quality of movement and abnormal neurological development, the fetal growth retardation results from at least one of chronic hypoxemia, circulatory insufficiency and malnutrition caused by placental and umbilical factors.
Response to Arguments
On p. 14-15 of the response, Applicant argues that: i) Bopardikar does not teach the claimed method because Bopardikar only describes methods of making a fetal polymix composition comprising two or more sources of mesenchymal stem cells (table in paragraph [0008], and co-cultured in a culture medium under hypoxic or normoxic conditions, and wherein the two or more sources include placenta, placental amnion, chorion, amniotic fluid or umbilical cord tissue, and only refers a brain disorder to cerebral palsy in paragraph [0015]; ii) Dezawa relates to Muse cells and Fan relates to cerebral palsy and fetal growth retardation.
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 §2131-2131.01, Bopardikar (US2017/0029770) does teach the claimed method because:
i. Bopardikar teaches a method of treating different diseases including cerebral palsy using the same material (i.e. a composition comprising fetal polymix of mesenchymal stem cells (MSCs) cultured under a hypoxic condition, wherein the fetal polymix-MSCs are SSEA-3+ and CD105+) and the same active step (administering to the subject) in the same patient population (i.e. cerebral palsy: a brain disorder associated with fetal growth retardation caused by chronic hypoxemia, circulatory insufficiency and malnutrition caused by placental and umbilical factors) as recited in instant claims 1-6 and 9-10 (see paragraphs [0015];[0056];[0058];[0104];[0138]; [0148]; [0157]-[0159]; [0191]-[0192]; claims 15 and 20-24).
Cerebral palsy is a brain disorder associated with fetal growth retardation that results from at least one of chronic hypoxemia, circulatory insufficiency and malnutrition caused by placental and umbilical factors as evidenced by Fan et al. (p. 473, 1st col., Risk factors and pathophysiological mechanisms to p. 474, 2nd col.; p. 474-478; Fan et al. Cell Transplantation, 2015; 24:471-485). The patients with cerebral palsy that results from chronic hypoxemia, circulatory insufficiency, and/or malnutrition caused by placental and umbilical factors have abnormal quality of movement and abnormal neurological development as in claims 1 and 9-10 as evidenced by Fan et al. (p. 473, 1st col., section: Risk factors and pathophysiological mechanisms to p. 474, 2nd col.; p. 474-478; Fan et al. Cell Transplantation, 2015; 24:471-485).
The fetal polymix-MSCs disclosed by Bopardikar are SSEA-3+ and CD105+ (SSEA-3+/CD105+-MSCs), and the SSEA-3+/CD105+-MSCs disclosed by Bopardikar are cultured under hypoxic condition (see paragraph [0003]), which is an external stress treatment as in claim 2 (i.e. culturing in a low oxygen concentration) in view of paragraph [0071] of the published specification. The SSEA-3+/CD105+-MSCs disclosed by Bopardikar are CD117-/CD146- as in claim 3, CD117-/CD146-/NG2-/CD34-/vWF-/CD271- as in claim 4 or CD34-/CD117-/CD146-/CD271-/ NG2-/CD34-/vWF-/Sox10-/Snai1-/Slug-/Tyrp1-/Dct- as in claim 5 and have the ability to engraft to brain tissue as in claim 6 (see paragraphs [0008], table; [0139]) and as also evidenced by Dezawa et al. (US2011/0070647; see paragraphs [0019]-[0023]; [0103]-[0109]; [0208], [0211], [0233]). Thus, the SSEA-3+/CD105+-MSCs disclosed by Bopardikar meet the limitation “pluripotent stem cells (PSCs) positive for SSEA-3 isolated from mesenchymal tissue or cultured mesenchymal cells of a living organism, CD105+, have the properties of low or non-existent telomerase activity, the ability to differentiate into any three germ layers, no neoplastic proliferation and self-renewal ability” recited in claims 1-6.
Thus, claims 1-6 and 9-10 are anticipated by Bopardikar as evidenced by Fan and Dezawa. Accordingly, the rejection of claims 1-6 and 9-10 under 35 U.S.C. 102(a)(1) & (a)(2) as being anticipated by Bopardikar as evidenced by Fan and Dezawa 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 1-6 and 9-10 are rejected under 35 U.S.C. 103 as being unpatentable over Bopardikar (US2017/0029770; issued as US11072776) in view of Dezawa (US2011/0070647) and evidentiary references: Fan (2015), Kirton (see abstract; Stroke, 2013; 44:3265-3271) and Camilo et al. (see abstract; Stroke, 2004; 35:1769-1775). The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 7-8 and 14-20 are rejected under 35 U.S.C. 103 as being unpatentable over Bopardikar (US2017/0029770; issued as US11072776) in view of Dezawa (US2011/0070647) and evidentiary references: Fan (2015), Kirton (2013) and Camilo (2004) as applied to claims 1-6 and 9-10 above, and further in view of Vawda et al. (Seminars in Fetal & Neonatal Medicine, 2007; 12:259-272) and Ahn et al. (Neonatology, 2016; 109:377-383. DOI:10.1159/000444905). The rejection is maintained for the reasons of record and the reasons set forth below.
Claims 7-8 stand rejected under 35 U.S.C. 103 as being unpatentable over Bopardikar (US2017/0029770; issued as US11072776) in view of Dezawa (US2011/0070647), Vawda (2007) and Ahn (2016) and evidentiary references: Fan (2015), Kirton (2013) and Camilo (2004) as applied to claims 1-10 and 14-20 above, and further in view of Sanberg (US2013/0045189). The rejection is maintained for the reasons of record and the reasons set forth below.
Response to Arguments
On p.15-16 of the response, Applicant argues that: i) Bopardikar does not teach the claimed method because Bopardikar only describes cells expressing SSEA-3+ and cells expressing CD105+ but does not describe administering cells that are both SSEA-3+ and CD105+ for a specific purposes; ii) Dezawa relates to Muse cells and refers to brain infarction; iii) Fan relates to mechanisms of cerebral palsy but does not provide guidance to a specific treatment using a cell preparation comprising a therapeutically effective amount of specific cells; iv) Kirton and Camilo only provide general information related to stroke and seizures, not a treatment of brain disorder associated with fetal growth retardation, which is different from cerebral palsy, cerebral hemorrhage and cerebral infarction; v) Vawda and Ahn relate to brain injuries/disorders but do not address brain disorder associated with fetal growth retardation resulting from at least one of chronic hypoxemia, circulatory insufficiency and malnutrition caused by placental and umbilical factors; vi) Sanberg teaches dosages but is related to neurodegenerative diseases such as stroke, which is a different disease and is not applicable to infants.
Applicant argues all 103 rejections together and thus the Examiner will answer and address Applicant’s arguments together.
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, Bopardikar and evidentiary references: Fan and Dezawa do teach the method recited in claims 1-6 and 9-10.
ii. 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 the SSEA-3+/CD105+-MSC disclosed by Bopardikar are not exactly identical to the claimed SSEA-3+/CD105+-PSCs that are not CD117(-) and CD146(-) as in claim 3; CD117(-), CD146(-), NG2(-), CD34(-), vWF(-) and CD271(-) as in claim 4 or CD117(-), CD146(-), NG2(-), CD34(-), vWF(-), Sox10(-), Snail(-), Slug(-), Tyrp-1 (-) and Dct(-) as in claim 5, Dezawa (US2011/0070647) teaches these limitations and provides motivation and an expectation of success in using the claimed SSEA-3+/CD105+-PSCs in Bopardikar’s method because Dezawa teaches methods of treating brain damages to the CNS using the claimed SSEA-3+/CD105+-PSCs.
Dezawa teaches a therapeutic method for treatment of a degenerative or traumatic neurologic disorders including damages to brain, damages to the CNS, ischemia, brain infarction, comprising administering to a patient in need thereof a therapeutically effective dose of a cell preparation comprising a cell fraction of SSEA-3+/CD105+-PSCs isolated from mesenchymal tissue of or cultured mesenchymal cells (see abstract; paragraphs [0142]-[0146]; [0132]-[0134]; [0016]-[0019]; [0019]-[0023], [0078]-[0079], [0206]-[0219]; p. 22, claims 1-24, in particular), wherein the SSEA-3+/CD105+-PSCs have the properties (i)-(v) recited in claim 1 and are CD117(-) and CD146(-) as in claim 3; CD117(-), CD146(-), NG2(-), CD34(-), vWF(-) and CD271(-) as in claim 4 and CD117(-), CD146(-), NG2(-), CD34(-), vWF(-), Sox10(-), Snail(-), Slug(-), Tyrp-1 (-) and Dct(-) as in claim 5 (see paragraphs [0019]-[0023]; [0103]-[0109]; [0208], [0211], [0233];in particular); and capable of engrafting into the brain tissue as in claim 6 (see paragraph [0132]); and wherein the effective dose is approximately 1x105 cells/individual (see paragraphs [0220], example 2), which meets or is within the claimed dose range of 1x105 to 1x108 cells/individual; or approximately 1x105 cells/kg to approximately 1x108 cells/kg per target individual recited in claims 7-8.
Note that the damages to brain, ischemia, brain infarction causes cerebral palsy or epilepsy as evidenced by Kirton et al. (see abstract; Stroke, 2013; 44:3265-3271) and Camilo et al. (see abstract; Stroke, 2004; 35:1769-1775).
A person of ordinary skill in the art would have recognized that selecting and applying the known SSEA-3+/CD105+-PSCs having the properties (i)-(v) recited in claim 1 and features recited in claims 3-6, the known methods of treating brain injuries or damages or disorders including cerebral palsy associated fetal growth retardation resulting from chronic hypoxemia, circulatory insufficiency, and/or malnutrition caused by placental and umbilical factors and the known technique disclosed by Dezawa to the Bopardikar’s method would have yielded the predictable result of ameliorating and/treating a brain disorder associated with fetal growth retardation resulting from chronic hypoxemia, circulatory insufficiency, and/or malnutrition caused by placental and umbilical factors in a subject in need thereof, and resulted in an improved method because SSEA-3+/CD105+-PSCs having the properties recited (i)-(v) of claim 1 and claims 2-6 have been shown to be effective to treat brain damage caused by ischemia or brain infarction or cerebral palsy, and cerebral palsy is caused by fetal growth retardation or fetal growth restriction resulting from chronic hypoxemia, circulatory insufficiency, and/or malnutrition caused by placental and umbilical factors.
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 SSEA-3+/CD105+-PSCs having the properties recited (i)-(v) of claim 1 and claims 2-6 and the known technique disclosed by Dezawa to the Bopardikar’s method, and yield the predictable result of ameliorating or treating brain damage including cerebral palsy caused by fetal growth retardation resulting from chronic hypoxemia, circulatory insufficiency, and/or malnutrition caused by placental and umbilical factors. See KSR International Co. V. Teleflex Inc. 82 USPQ2d 1385 (2007), In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980); In re Crockett, 279 F.2d 274, 126 USPQ 186 (CCPA 1960); Ex parte Quadranti, 25 USPQ2d 1071 (Bd. Pat. App. & Inter. 1992), Sinclair & Carroll Co. v. Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945) and In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) and also see MPEP § 2143. 01-I, MPEP § 2144.06 and MPEP §2144.07.
Accordingly, the rejection of claims 1-6 and 9-10 under 35 U.S.C. 103 as being unpatentable over Bopardikar in view of Dezawa and evidentiary references: Fan, Kirton and Camilo is maintained.
iii. While Bopardikar and Dezawa do not teach human neonate or infant recited in claims 7-8 and 14, Vawda and Ahn teach these limitations and provide motivation and an expectation of success in treating human neonate or infants using the method of Bopardikar and Dezawa for ameliorating or treating a brain disorder or brain damage associated with fetal growth retardation caused by chronic hypoxemia, circulatory insufficiency and malnutrition caused by placental and umbilical factors because Vawda and Ahn teach treating perinatal brain injuries or damages including cerebral palsy, developmental disabilities, extended labor or repeated asphyxia after birth (i.e. chronic hypoxemia, circulatory insufficiency and malnutrition caused by placental and umbilical factors), or neonatal brain disorders including neonatal brain injury caused by intraventricular hemorrhage or hypoxic-ischemic encephalopathy injuries or neonatal stroke using SSEA-3+ pluripotent stem cells or CD105+ stem cells or pluripotent stem cells from umbilical cord blood-derived mesenchymal stem cells (MSCs) at an effective dose of at least 5x105 cells per dose, 1x106 cells per dose or 5x106 cells/kg per dose or 1x107 cells/kg per dose (see abstract; p. 259-267 in Vawda and abstract; p. 378-381 in Ahn).
A person of ordinary skill in the art would have recognized that selecting and applying the known SSEA-3+/CD105+-PSCs having the properties (i)-(v) recited in claim 1 and features recited in claims 3-6, the known methods of treating brain injuries or damages or disorders including cerebral palsy, developmental disabilities, extended labor or repeated asphyxia after birth or perinatal brain injuries or damages associated fetal growth retardation, and the known technique of treating in human neonate or infants disclosed by Vawda and Ahn to the method of Bopardikar and Dezawa would have yielded the predictable result of ameliorating and/treating a brain disorder or perinatal brain damage associated with fetal growth retardation in a human neonate subject in need thereof, and resulted in an improved method because SSEA-3+/CD105+-PSCs having the properties recited (i)-(v) of claim 1 and claims 2-6 have been shown to be effective to treat brain damage including cerebral palsy, developmental disabilities, extended labor or repeated asphyxia after birth or perinatal brain damage associated with fetal growth retardation or fetal growth restriction, thereby improves intellectual disability or mental development delay, learning disability or memory learning and visual cognitive memory due to perinatal brain damage.
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 SSEA-3+/CD105+-PSCs having the properties (i)-(v) recited in claim 1 and features recited in claims 3-6, the known methods of treating brain injuries or damages or disorders including cerebral palsy, developmental disabilities, extended labor or repeated asphyxia after birth or perinatal brain injuries or damages associated fetal growth retardation and the known technique disclosed by Vawda and Ahn to the method of Bopardikar and Dezawa, and yield the predictable result of ameliorating and/treating a brain disorder or perinatal brain damage associated with fetal growth retardation in a human neonate or infant in need thereof for improving intellectual disability or mental development delay, learning disability or memory learning and visual cognitive memory or treating cerebral palsy, developmental disabilities, infection, extended labor or repeated asphyxia after birth.
Accordingly, the rejection of claims 7-8 and 14-20 under 35 U.S.C. 103 as being unpatentable over Bopardikar in view of Dezawa, Vawda and Ahn, and evidentiary references: Fan, Kirton and Camilo is maintained.
iv. While Bopardikar, Dezawa, Vawda and Ahn do not teach a cell dose range that is exactly identical to the claimed range of 1x105-1x108 cells/individual or 1x105-1x108cells/kg per target individual as in claims 7-8, Dezawa teaches a dose range of approximately 1x105 cells/individual (see paragraphs [0220], example 2), Ahn teaches at least 5x105 cells per dose or 1x106 cells per dose, or 5x106 cells/kg per dose or 1x107 cells/kg (see abstract; p. 380-381, in particular) for treating brain damage, ischemia, perinatal brain damage including cerebral palsy, developmental disabilities, infection, extended labor or repeated asphyxia after birth, and Sanberg teaches the use of human neural stem cells in an amount of the range of about 1x104 to about 1x109 cells, about 1x105 to about 1x107 or about 2x105 to about 8x106 for treating neurodegenerative diseases including traumatic brain injury, ischemia and stroke, which are brain damage causing cerebral palsy (see abstract; paragraphs [0046]-[0047], [0037]; p. 8-9, claims 1-23).
A person of ordinary skill in the art would have recognized that selecting and applying the known dose ranges and technique disclosed by Dezawa and Sanberg to the method of Bopardikar, Dezawa, Vawda and Ahn would have yielded the predictable result of ameliorating and/treating a brain disorder or perinatal brain damage associated with fetal growth retardation in a subject including a human neonate or infant in need thereof for improving intellectual disability or mental development delay, learning disability or memory learning and visual cognitive memory and resulted in an improved method because different dose ranges including 1x105 cells/individual, at least 5x105 cells per dose, 1x106 cells per dose, or 5x106 cells/kg per dose or 1x107 cells/kg or about 1x104 to about 1x109 cells have been shown to successfully treat brain injury or damage including cerebral palsy, developmental disabilities, infection, extended labor or repeated asphyxia after birth or pediatric traumatic brain injury (TBI), hypoxic ischemic encephalopathy which causes cerebral palsy.
Further, routine optimization of Dezawa’s dose ranges, Ahn’s dose ranges, and Sanberg’s dose ranges would have led to the claimed range of 1x105-1x108 cells/individual or 1x105-1x108 cells/kg per target individual because Sanberg teaches the use of different dose ranges including 1x105 cells/individual, at least 5x105 cells per dose, 1x106 cells per dose, or 5x106 cells/kg per dose or 1x107 cells/kg or about 1x104 to about 1x109 cells for treating brain injury or damage including cerebral palsy, developmental disabilities, extended labor or repeated asphyxia after birth or pediatric traumatic brain injury (TBI), hypoxic ischemic encephalopathy. The person of ordinary skill in the art would have found it obvious to optimize within the range taught by Sanberg because Sanberg teaches that this entire range treat brain damages and also teaches how to optimize the cell dose ranges. It is obvious and not inventive to discover the optimum or workable ranges by routine experimentation because the results are expected. Note that “[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105USPQ 233, 235 (CCPA 1955)” See MPEP 2144.05-II.
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 dose ranges and technique disclosed by Sanberg, Dezawa and Ahn to the method of the method of Bopardikar, Dezawa, Vawda and Ahn to ameliorate or treat brain injuries or damages or disorders including cerebral palsy, developmental disabilities, extended labor or repeated asphyxia after birth, or perinatal brain damage associated fetal growth retardation in a subject including a human neonate or infant in need thereof and yield the predictable result of ameliorating or treating brain injuries or damages or disorders including cerebral palsy, developmental disabilities, extended labor or repeated asphyxia after birth or perinatal brain damage associated fetal growth retardation in a subject including a human neonate or infant in need thereof and improving intellectual disability or mental development delay, learning disability or memory learning and visual cognitive memory.
Accordingly, the rejection of claims 7-8 under 35 U.S.C. 103 as being unpatentable over Bopardikar in view of Dezawa, Vawda, Ahn and Sanberg, and evidentiary references: Fan, Kirton and Camilo is maintained.
Conclusion
9. NO CLAIM IS ALLOWED.
10. THIS ACTION IS MADE FINAL. 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 nonprovisional extension fee (37 CFR 1.17(a)) 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 mailing date of this final action.
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 on Monday-Thursday, 7:00am-5:30pm 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, Jeffrey Stucker, can be reached on 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Chang-Yu Wang
July 8, 2025
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
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