DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
This action is in response to the papers filed September 23, 2024.
Claims 1-20 and 42-45 are currently pending in the application and examined on the merits.
Priority
The present application is a 35 U.S.C. 371 national stage filing of International Application No. PCT/US2021/054362, filed October 11, 2021.
Applicant’s claim for the benefit of a prior-filed parent provisional applications 63/090,671 filed 10/12/2020 under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged.
Thus, the earliest possible priority for the instant application is October 12, 2020.
Claim Objections
Claims 1, 2, 5, 7, 10, 13, and 42-45 are objected to because of the following informalities:
Claim 1, 2, 5, 7, 42, 43, 44 and 45 recites acronyms such as “NR1” and “ES-derived.” The first time an acronym is utilized in a claim-set, said acronym should be spelled out in its entirety followed by said acronym in parenthesis (e.g. embryonic stem cell (ES)).
Claims 10 and 13 recite a list of proteins. The first time an acronym is utilized in a claim-set, said acronym should be spelled out in its entirety followed by said acronym in parenthesis (e.g. Neuregulin 3 (NRG3)).
Claim 45 recites acronyms such as “LIF” or “PHS.” The first time an acronym is utilized in a claim-set, said acronym should be spelled out in its entirety followed by said acronym in parenthesis (e.g. Pooled Human Serum (pHS)).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-20 and 42-45 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “NR1 ES-derived neural stem cells” in claim 1, 2, 5, 7, 42, 43, 44 and 45 is used by the claim to mean that the NR1 cells are derived from the ES cells, which are neural stem cells while it can also be read as “NR1 ES cells” having neural cells derived from them. Moreover, NR1 is a term which is not defined by the claim and therefore is indefinite. It is unclear what the metes and bounds of NR1 is as NR1 could be meant to be the cell type produced by a specific method, or NR1, another name for GRIN1, a glutamate receptor.
Claim 1 recites “which cells express trophic factors.” It is unclear which cell the limitation refers to. Either the ES or the neural stem cell.
Claim 2 recites “isolated,” however, it is unclear what these cells are isolated from or to what extent they are isolated.
Claim 13 which depends on claim 11 recites the limitation “wherein the extracellular matrix protein.” However, claim 11, does not recite the term “extracellular matrix protein” and thus, claim 13 lacks antecedent basis. It is noted that claim 12 recites “extracellular matrix protein” and would have antecedent basis for claim 13.
Claim 19 which depends on claim 17 recites the limitation “wherein reversing the impaired mobility.” However, claim 11, does not recite the term “reversing the impaired mobility” and thus, claim 19 lacks antecedent basis.
Claim 20 which depends on claim 1 recites the limitation “wherein the brain lesion.” However, claim 11, does not recite the term “brain lesion” and thus, claim 20 lacks antecedent basis.
Claim 45 recites the trade name “Glutamax.” Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a L-glutamine alternative, L-alanyl l glutamine, and, accordingly, the identification/description is indefinite.
Therefore, independent claims 1 and 45, and their dependent claims are rejected as being indefinite.
Claim Rejections - 35 USC § 102
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.
Claim 1-7, 9-20, and 42-44 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Azevedo-Pereira (Stroke 50.Suppl_1 (2019): ATP142-ATP142) as evidenced by Andres (Brain 2011: 134; 1777–1789)
Regarding claim 1, Azevedo-Pereira teaches administering NR1 (hES-derived) human neural cells to pre-clinical stroke models which resulted in restoring circuit excitability (i.e. restore neurologic function) (p. 1). Azevedo-Pereira further teaches that the transplantation of the NR1 cells resulted in different gene expression in all cortical layers (i.e. augment endogenous neural repair) (p. 1). As evidenced by the instant specification, NR1 cells are inherently produced from H9 cell line with a normal karyotype (para. 0062).
Regarding claim 2, as Azevedo-Pereira teaches administering NR1 (hES-derived) human neural cells, it is interpreted that these cells are in an isolated composition for therapeutic use.
Regarding claim 3 and 4, Azevedo-Pereira teaches administering NR1 cells to an ischemic cortex of a brain (i.e. cortical transplantation)(p. 1). Therefore, the subject has suffered an ischemic stroke.
Regarding claim 5, Azevedo-Pereira teaches the ischemic stroke is produced by distal middle cerebral artery occlusion before administering NR1 cells to an ischemic cortex of a brain (p. 1, 1st half). Therefore, the ischemic cortex would be the cerebral cortex or near it.
Regarding claims 6 and 9, Azevedo-Pereira teaches the peri-infarct motor cortex is part of the ischemic cortex (p. 1, 1st half).
Regarding claim 7, Azevedo-Pereira teaches administering the cells 1 week after distal middle cerebral artery occlusion (p. 1, 1st half)
Regarding claims 10-14, although Azevedo-Pereira does not teach the specific proteins and secreted trophic factors, these are inherent to the NR1 cells claimed. As seen in the instant application’s Figure 22 and Table 10, these are inherent to the NR1 cells of Azevedo-Pereira’s characterization and secretome. As evidenced by Andres, factors such as VEGF are known in the art to have the property of enhancing structural plasticity (p. 1778, Figure 4). Moreover, axonal transport, which is critical for both proper axonal function and axonal sprouting, is inhibited by stroke and that this is rescued by the stem cell treatment through their secreted factors (Abstract, Figure 4).
Regarding claim 15 and 16, Azevedo-Pereira teaches that neurological recovery was accessed by the Whisker-paw test which showed NR1 enhances post-stroke behavioral recovery post transplantation (p. 1, 1st half). As Whisker-paw tests involve upper extremity motion, it is an improvement in upper extremity function in raising or lifting.
Regarding claims 17-19, although Azevedo-Pereira does not teach the gait improvements and reversal of impaired mobility, these are inherent to the NR1 cells being administered to a subject in need there of as claimed. As each and every limitation is taught by Azevedo-Pereira, the same method steps yield the same results.
Regarding claim 20, as seen above, “brain lesion” lacks antecedent basis and therefore, it is unclear and indefinite. However, it is interpreted as part of the stroke condition and therefore does not structurally limit the method of treatment with an active step.
Regarding claims 42-43, Azevedo-Pereira teaches administering NR1 (hES-derived) human neural cells to pre-clinical stroke models which resulted in restoring circuit excitability (i.e. restore neurologic function) (p. 1). Therefore, it is interpreted that Azevedo-Pereira reads on an isolated composition of NR1 cells which secrete trophic factors.
Regarding claim 44, Azevedo-Pereira teaches administering NR1 (hES-derived) human neural cells to pre-clinical stroke models which resulted in restoring circuit excitability (i.e. restore neurologic function) (p. 1). As the control is a “vehicle” only (p. 1, line 4) it is interpreted that the vehicle (i.e. pharmaceutically acceptable carrier) is present in the NR1 cell composition. Therefore, it is interpreted that Azevedo-Pereira reads on an isolated composition of NR1 cells which secrete trophic factors with a pharmaceutically acceptable carrier.
Therefore, the invention is anticipated by Azevedo-Pereira.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim 1-20, and 42-44 are rejected under 35 U.S.C. 103 as being unpatentable over Azevedo-Pereira (Stroke 50.Suppl_1 (2019): ATP142-ATP142) as evidenced by Andres (Brain 2011: 134; 1777–1789; IDS reference) in view of Wechsler (Stroke. 2018;49:1066-1074).
Regarding claim 1, Azevedo-Pereira teaches administering NR1 (hES-derived) human neural cells to pre-clinical stroke models which resulted in restoring circuit excitability (i.e. restore neurologic function) (p. 1). Azevedo-Pereira further teaches that the transplantation of the NR1 cells resulted in different gene expression in all cortical layers (i.e. augment endogenous neural repair) (p. 1). As evidenced by the instant specification, NR1 cells are inherently produced from H9 cell line with a normal karyotype (para. 0062).
Regarding claim 2, as Azevedo-Pereira teaches administering NR1 (hES-derived) human neural cells, it is interpreted that these cells are in an isolated composition for therapeutic use.
Regarding claim 3 and 4, Azevedo-Pereira teaches administering NR1 cells to an ischemic cortex of a brain (i.e. cortical transplantation)(p. 1). Therefore, the subject has suffered an ischemic stroke.
Regarding claim 5, Azevedo-Pereira teaches the ischemic stroke is produced by distal middle cerebral artery occlusion before administering NR1 cells to an ischemic cortex of a brain (p. 1, 1st half). Therefore, the ischemic cortex would be the cerebral cortex or near it.
Regarding claims 6 and 9, Azevedo-Pereira teaches the peri-infarct motor cortex is part of the ischemic cortex (p. 1, 1st half).
Regarding claim 7, Azevedo-Pereira teaches administering the cells 1 week after distal middle cerebral artery occlusion (p. 1, 1st half)
However, regarding claim 8, Azevedo-Pereira does not teach administration to the subcortical area of the brain such as the hippocampus, amygdala, extended amygdala, claustrum, basal ganglia, or basal forebrain.
Wechsler teaches clinical studies for stroke which administer neuronal cells to the basal ganglia surrounding the infarct using a stereotactic technique and improvement in clinical scales was observed (p. 1068-1069, bridging paragraph).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to administer the NR1 cells of Azevedo-Pereira to the basal ganglia (i.e. subcortical region) as taught by Wechsler in order to treat conditions of stroke. An artisan would have been motivated to do so as Wechsler teaches after administration to the basal ganglia, improvement in clinical scales was observed (p. 1068-1069, bridging paragraph).
Regarding claims 10-14, although Azevedo-Pereira does not teach the specific proteins and secreted trophic factors, these are inherent to the NR1 cells claimed. As seen in the instant application’s Figure 22 and Table 10, these are inherent to the NR1 cells of Azevedo-Pereira’s characterization and secretome. As evidenced by Andres, factors such as VEGF are known in the art to have the property of enhancing structural plasticity (p. 1778, Figure 4). Moreover, axonal transport, which is critical for both proper axonal function and axonal sprouting, is inhibited by stroke and that this is rescued by the stem cell treatment through their secreted factors (Abstract, Figure 4).
Regarding claim 15 and 16, Azevedo-Pereira teaches that neurological recovery was accessed by the Whisker-paw test which showed NR1 enhances post-stroke behavioral recovery post transplantation (p. 1, 1st half). As Whisker-paw tests involve upper extremity motion, it is an improvement in upper extremity function in raising or lifting.
Regarding claims 17-19, although Azevedo-Pereira does not teach the gait improvements and reversal of impaired mobility, these are inherent to the NR1 cells being administered to a subject in need there of as claimed. As each and every limitation is taught by Azevedo-Pereira, the same method steps would yield the same predictable results with a reasonable expectation of success.
Regarding claim 20, as seen above, “brain lesion” lacks antecedent basis and therefore, it is unclear and indefinite. However, it is interpreted as part of the stroke condition and therefore does not structurally limit the method of treatment with an active step.
Regarding claims 42-43, Azevedo-Pereira teaches administering NR1 (hES-derived) human neural cells to pre-clinical stroke models which resulted in restoring circuit excitability (i.e. restore neurologic function) (p. 1). Therefore, it is interpreted that Azevedo-Pereira reads on an isolated composition of NR1 cells which secrete trophic factors.
Regarding claim 44, Azevedo-Pereira teaches administering NR1 (hES-derived) human neural cells to pre-clinical stroke models which resulted in restoring circuit excitability (i.e. restore neurologic function) (p. 1). As the control is a “vehicle” only (p. 1, line 4) it is interpreted that the vehicle (i.e. pharmaceutically acceptable carrier) is present in the NR1 cell composition. Therefore, it is interpreted that Azevedo-Pereira reads on an isolated composition of NR1 cells which secrete trophic factors with a pharmaceutically acceptable carrier.
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
Claim 45 is rejected under 35 U.S.C. 103 as being unpatentable over Chen (Methods Mol Biol, 2019:1919:59-72) in view of Gonzalez (Methods Mol Biol, 2019:1919:43-58)
As the specification describes NR1 cells being made from H9 cells, the claim is interpreted as H9 cells cultured under the claimed conditions to produce the claimed NR1 cells derived from the ES H9 cells as NR1 ES cells which the NR1 ES derived neural stem cells are made from.
Regarding claim 45, Chen teaches a method of making human neural stem cells from H9 cells (Abstract). The H9 cells were cultured on plates (i.e. solid supports) in neural induction media of DMEM/F12 media, N2 supplement, B27 supplement, and without feeder cells, RA, EGF, FGF, LIF, or PHS (p. 68, steps 7-8).
However, Chen does not teach that Glutamax is utilized.
Gonzalez teaches that Glutamax is utilized with N2 and B27 supplements as neural induction media (Table 2, p. 45).
It would have been obvious to one of ordinary skill in the art at the time of the effective filing date to add Glutamax as taught by Gonzalez to the neural induction medium of Chen with a reasonable expectation of success. An artisan would have been motivated to do so, as Gonzalez teaches it is known in the art to utilize Glutamax with N2 and B27 (which are found within Chen’s induction media) in neural induction media (Table 2).
Therefore, the invention would have been obvious to one of ordinary skill in the art at the time of the effective filing date.
Conclusion
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/ALEXANDRA F CONNORS/Examiner, Art Unit 1634
/JAMES D SCHULTZ/Supervisory Patent Examiner, Art Unit 1631