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 .
Response to Amendment
In the amendment dated 07/17/2025, the following has occurred:
Claims 1, are amended,
Claim 3 is cancelled, and
Claims 1-2 and 4-10 are pending.
Response to Arguments
Applicant's arguments filed 12/05/2024 have been fully considered but they are not persuasive.
The applicant asserts that the “statements in Singh do not actually teach or suggest a "polymer scaffold configured to hold living stem cells for the stem cell therapy" as recited in amended claim 1. The examiner respectfully disagrees since Singh discloses “the support scaffold can be formed from poly(lactic-co-glycolic acid) (PLGA) and can be configured…within the target tissue” where “the support scaffold…can be coated with a drug” (par. [0087]). This combined with the disclosure of “The term "drug" …refers to any functional agent that can be delivered…including …stem cells” (par. [0101]), therefore discloses a neural implant polymer scaffold that holds stem cells for therapy as recited in claim 1. Thus Singh rejection is maintained.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claims 1-4, 7 and 9 are rejected under 35 U.S.C. 103 as being unpatentable over Singh et al. (Publication No. US 2015/0038949 A1, hereinafter “Singh”) in view of Fischell (Publication No. US 2014/0081348 A1).
Regarding claim 1, Singh discloses the apparatus for providing in vivo neural therapy, the apparatus comprising:
a neural implant (Figs. 1 and 4 (10), (40) and pars. [0030]: FIG. 4 is a schematic view of the device of FIG. 1 inserted into tissue, [0079]: …device 10 can be used to deliver a drug-containing fluid …to a target tissue region. FIG. 4 illustrates an exemplary method for convection-enhanced delivery of a drug to target tissue 40 in a patient's brain) configured to simultaneously provide a) in vivo electrical stimulation to a brain of a subject (Fig. 1 (24) and par. [0089]: One or more electrodes 24 can also be provided in or on the fluid conduit 12, the sheath 14, or the scaffold, which can be used to deliver electrical energy to target tissue, e.g., to stimulate the target tissue…), and b) stem cell therapy to the brain of the subject (pars. [0089]: …electrical energy is delivered through an electrode 24 while a drug is simultaneously delivered through the fluid conduit 12, [0101]: …"drug" as used herein refers to any functional agent that can be delivered to a human or animal patient, including…stem cells…); and
an electrical connection unit configured to be affixed to the head of the subject (Figs. 32 and 35 and par. [0136]: …the system 700 can include a crosscutaneous or percutaneous access device 702…a skull anchor 712…) and electrically connected to the neural implant (Figs. 32 and 36 (708), (714) and par. [0136]: …the system 700 can include a crosscutaneous or percutaneous access device 702…and one or more microfluidic catheters or CED devices 714 (shown in FIG. 36). The system 700 is configured for long-term implantation beneath the skin 716 of a patient, with the catheters 714 extending into the brain, spinal column, or other target region of the patient and the access device 702 extending at least partially through the skin) , wherein the electrical connection to the neural implant is via a cannula through a skull of the subject (Fig. 36 and par. [0136]: … electrical connections can be made through the access device 702 to apply energy to one or more electrodes on the catheters 714 or to read sensor information from one or more sensors on the catheters 714).
wherein the electrical connection unit is configured to provide stimulation to stem cells in the neural implant after the neural implant is implanted in the brain of the subject (Fig. 36 (714) (716) and par. [0136]: delivery and/or monitoring system 700 which can be used with any …microfluidic catheters or CED devices 714… is configured for long-term implantation beneath the skin 716 of a patient… In use, fluids containing drugs or other therapeutic agents can be…delivered to the target site within the patient, e.g., via convection-enhanced delivery. In addition, electrical connections can be made through the access device 702 to apply energy to one or more electrodes on the catheters 714…; CED device 714 implanted in brain of patient 716 where stem cells (drugs) are implanted and electrical energy is applied to implanted CED device through electrodes);
wherein the neural implant includes a polymer scaffold (Singh, pars. [0011], [0087]: … The support scaffold can be rigid or semi-rigid and can be formed from a degradable thermoplastic polymer, for example, a degradable thermoplastic polyester or a degradable thermoplastic polycarbonate. In some embodiments, the support scaffold can be formed from poly(lactic-co-glycolic acid) (PLGA) configured to hold living stem cells for the stem cell therapy (Singh, par. [0088] …the support scaffold can contain or can be impregnated with a quantity of a drug…or in addition, a surface of these components can be coated with a drug, [0101]: …"drug" as used herein refers to any functional agent that can be delivered to a human or animal patient, including…stem cells).
Singh does not expressly disclose a reference electrode disposed on a head of the subject at a reference location spaced apart from an 10implant location of the neural implant; and
an electrical connection unit electrically connected to the neural implant and to the reference electrode;
However, Fischell in the same field of endeavor: low frequency in vivo neural stimulation device, discloses a reference electrode disposed (Fig. 2 (220), (226) and pars. [0032]: …where the neurostimulator (110) is implantable, it may be implanted in any suitable location…FIG. 2 shows one variation of an implantable neurostimulation system (200) in which the components of the neurostimulator (110) may be contained within an implantable housing (220), [0033], [0034]: …one or more portions of the neurostimulator housing (220) may act as an electrode, which may serve as a reference electrode ) on a head of the subject at a reference location spaced apart from an implant location of the neural implant (Fig. 2 and par. [0034]: … the stimulation system (200) may be programmed and configured to use some or all of the electrodes (160)-(163) of the first bifurcation (224) and the electrodes (164)-(167) of the second bifurcation (226) …while the electrodes (168)-(171) of the cortical strip lead (228) may be configured to act as sensing electrodes ); and
an electrical connection unit affixed to the head of the subject and electrically connected to the neural implant and to the reference electrode (par. [0032]: …a second cortical strip lead (228). The first lead (223) and the second lead (728) may each be coupled to the neurostimulator (110) at a lead connector or a lead interface (222)), wherein the electrical connection to the neural implant is via a cannula through a skull of the subject (par. [0032]: The two bifurcations (224) and (226) of the first lead (223) and the second lead (228) each may access the brain through one or more burr holes (250) (two burr holes (250) are shown in FIG. 2) formed in the cranium, and may be used to position one or more electrodes (160)-(171) positioned on a distal portion of a lead relative to the brain) to provide the benefit of a monopolar stimulation pathway for delivering stimulation in either a responsive or non-responsive modes (par. [0034]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to include in the neural therapy delivery device of Singh, a reference electrode electrically connected as taught by Fischell, in order to provide the benefit of a monopolar stimulation pathway for delivering stimulation in either a responsive or non-responsive modes.
Regarding claim 2, Singh discloses the apparatus of claim 1, except wherein the reference location is opposite the implant location relative to the head of the subject.
Fischell discloses the reference location (Fig. 2 (110)) is substantially opposite the implant location (Fig. 2 (250)) relative to the head of the subject (Fig. 2 (110), (220), (250); the reference location 110 is located on the lower right of the cranium while the implant location is on the upper left side of the cranium) for the purpose of delivering one or more stimulation signals through a stimulation pathway through the brain (par. [0034]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to modify the neural therapy delivery device having a reference electrode as taught by Singh and Fischell, to include the reference electrode location opposite the implant location as taught by Fischell, in order to deliver one or more stimulation signals on a stimulation pathway through the brain.
Regarding claim 4, the Singh and Fischell combination discloses the apparatus of claim 3, wherein the neural implant is configured to provide in vitro electrical stimulation (Singh, par. [0089]: One or more electrodes 24 can also be provided…electrical energy is delivered through an electrode 24 ) to the living stem cells prior to being disposed on the brain of the subject (Singh, pars. [0088]: ...the fluid conduit 12…can contain or can be impregnated with a quantity of a drug, [0101]: …"drug" as used herein refers to any functional agent that can be delivered to a human or animal patient, including…stem cells…). Note: Singh's neural implant is capable of providing in vitro electrical stimulation to living stem cells prior to being disposed on the brain of the subject since the neural implant contains stem cells and delivers electrical stimulation in the area of stem cells.
Regarding claim 7, Singh discloses the apparatus of claim 1, except wherein the in vivo electrical stimulation is an AC electrical stimulation.
Fischell discloses the in vivo electrical stimulation (Fig. 2, (200), (226)) is an AC electrical stimulation (pars. [0048], [0050]: The low-frequency stimulation signal of the first non-responsive stimulation mode may be any suitable signal. The stimulation signal may be pulsatile, non-pulsatile (e.g., sinusoidal or quasi-sinusoidal waveforms)…) for the benefit of delivering a responsive or non-responsive stimulation mode (par. [0036]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to use in the neural stimulation apparatus of Singh, AC electrical stimulation as taught by Fischell in order to deliver a responsive or non-responsive stimulation mode.
Regarding claim 9, the Singh and Fischell combination discloses the apparatus of claim 1, wherein the neural implant is configured to release one or more chemical agents to the brain of the subject in vivo (Singh, Fig. 4 pars. [0095]: The device 10 can be used to deliver a drug-containing fluid …to a target tissue region. FIG. 4 illustrates an exemplary method for convection-enhanced delivery of a drug to target tissue 40 in a patient's brain, [0101]: …"drug" as used herein refers to any functional agent that can be delivered to a human or animal patient, including…chemicals).
Claim 5 is rejected under 35 U.S.C. 103 as being unpatentable over Singh in view of Fischell, as applied to claims 1-2, 4, 7 and 9 above, and further evidenced by Huang et al. (“Electrical Stimulation Elicits Neural Stem Cells Activation: New Perspectives in CNS Repair,” cited by applicant, hereinafter “Huang”) and Park et al. (“Increased Neuronal Proliferation in the Dentate Gyrus of Aged Rats Following Neural Stem Cell Implantation,” cited by applicant, hereinafter “Park”).
Regarding claim 5, the Singh and Fischell combination discloses the apparatus of claim 1, wherein the in vivo electrical stimulation and stem cell therapy are configured to promote endogenous stem cell production (Singh, Fig. 1 and par. [0089]: …electrical energy is delivered through an electrode 24 while a drug is simultaneously delivered through the fluid conduit 12, [0101]: …"drug" as used herein refers to any functional agent that can be delivered to a human or animal patient, including…stem cells…). Note: Singh's neural implant device is capable of providing in vivo electrical stimulation to promote endogenous stem cell production since stimulation and stem cell therapy are known in the art to promote endogenous stem cell production as is evidenced by Huang, which discloses electrical stimulation as a means to increase endogenous stem cell production in CNS tissue in vivo (see section EXOGENOUS ELECTRICAL CURRENTS MOBILIZE NSCs/NPCs IN VIVO MODELS: …when [neural stem cells]/[neural precursor cells] are…in vivo, astrocytes become activated, resume proliferating…), and also evidenced by Park, which discloses increased endogenous stem cell production in vivo in neural tissue as a result of stem cell therapy (Fig. 1 and Abstract: …implants of exogenous NSCs may promote regeneration…through stimulation of endogenous neurogenesis).
Claims 6 and 8 are rejected under 35 U.S.C. 103 as being unpatentable over Singh in view of Fischell as applied to claims 1-5, 7 and 9 above, and further in view of Martin et al. (Publication No. US 2007/0060815 A1, hereinafter “Martin”).
Regarding claim 6, the Singh and Fischell combination discloses the apparatus of claim 1, wherein the stem cell therapy comprises providing chemical signals to the brain of the subject (Singh, Fig. 4 pars. [0095]: The device 10 can be used to deliver a drug-containing fluid …to a target tissue region. FIG. 4 illustrates an exemplary method for convection-enhanced delivery of a drug to target tissue 40 in a patient's brain, [0101]: …"drug" as used herein refers to any functional agent that can be delivered to a human or animal patient, including…chemicals).
The Singh and Fischell combination does not disclose providing chemical signals to the brain of the subject with stem cells in the neural implant.
However, Martin, in the same field of endeavor: biological integrated stimulation, discloses providing chemical signals to the brain of the subject with stem cells in the neural implant (Fig. 5 and par. [0058]: …the biocompatible implantable electrode comprises hydrogel seeded with one or more biological components…living stem cells… space-filling bioelectrodes can be implanted into living tissue, for example in the brain…living stem cells which can provide…growth factor secretion…) for diverse benefit of promoting local tissue regeneration, recruitment of endogenous stem cells to the brain tissue near the implant site (par. [0058]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to provide with the stem cells of the neural implant of Singh and Fischell, living stem cells that secrete chemical signals, as taught by Martin, in order to provide the diverse benefit of promoting local tissue regeneration, recruitment of endogenous stem cells to the brain tissue near the implant site.
Regarding claim 8, the Singh, Fischell and Martin combination discloses all of the apparatus of claim 7, except wherein the AC electrical stimulation has a frequency in a range from 1 Hz to 300 Hz.
Fischell discloses the AC electrical stimulation (Fig. 2, (200), (226) and pars. [0048], [0050]: The low-frequency stimulation signal of the first non-responsive stimulation mode may be any suitable signal. The stimulation signal may be pulsatile, non-pulsatile (e.g., sinusoidal or quasi-sinusoidal waveforms)…) has a frequency in a range from 1 Hz to 300 Hz (par. [0053]: ……the stimulation signal may have a primary frequency between 15 Hz and 200 Hz) for the benefit of delivering a responsive or non-responsive stimulation mode (par. [0036]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to use in the neural stimulation apparatus of Singh and Martin, AC electrical stimulation in the range of 15 to 200 Hz as taught by Fischell in order to deliver a responsive or non-responsive stimulation mode.
Claim 10 is rejected under 35 U.S.C. 103 as being unpatentable over Singh in view of Fischell as applied to claims 1-5, 7 and 9 above, and further in view of Schussler (Publication No. US 2022/0081677 A1).
Regarding claim 10, the Singh and Fischell combination discloses the apparatus of claim 1, except wherein the stem cells in the neural implant release one or more paracrine factors responsive to stimulation from the electrical connection unit.
However, Schussler, in the same field of endeavor, method for delivering mesenchymal stem cells, discloses the stem cells in the neural implant release one or more paracrine factors responsive to stimulation from the electrical connection unit (pars. [0114]: …said method being further characterised in that [0115]: ...inducing the differentiation of multipotent mesenchymal stem cells to contractile cells comprises contacting the mesenchymal stem cells with at least one agent promoting differentiation chosen…electrical stimulation…, [0117]: …inducing a paracrine activity of said contractile cells) for the purpose of promoting tissue regeneration in vivo (par. [0093]).
Therefore, it would have been obvious to one having ordinary skill in the art before the effective filing date of the claimed invention, to modify the neural stimulation apparatus of Singh and Fischell, to release paracrine activity by electrical stimulation as taught by Schussler in order to promoting tissue regeneration in vivo.
Conclusion
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.
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/AAA/Examiner, Art Unit 3796
/NIKETA PATEL/Supervisory Patent Examiner, Art Unit 3792