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 .
Applicant’s amendment filed on 10/22/2025 has been entered.
Amended claims 1 and 3-37 are pending in the present application.
Applicant elected previously without traverse of Group I, which is drawn to a method of treatment recited in independent claim 1.
Applicant also elected previously without traverse the following species: (i) administration by inhalation; (i) one or more neurodegenerative disorders; (iii) traumatic brain injury (TBI); (iv) one or more cell pathway inhibitors together with one or more complement pathway inhibitors and one or more TGFβ inhibitors; (v) ROCK inhibitors; (vi) C1 esterase inhibitors; (vii) cultured stem cells; (viii) slow release nanoparticles; (ix) biodegradable liposomes; and (x) further comprising the step of administering gene therapy.
Claims 3, 13-14, 16 and 19-37 were withdrawn previously because they are directed to non-elected inventions and non-elected species.
Accordingly, amended claims 1, 4-12, 15 and 17-18 are examined on the merits herein with the above elected species.
Priority
The present application is a CIP of US application with the Serial Number 16/398,174, filed on 04/29/2019, now US Patent 10842669; which claims benefit of the provisional application 62/839738, filed on 04/28/2019; the present application is also a CIP of US application with the Serial Number 15/439,343, filed on 02/22/2017, now abandoned; the 16/398,174 is a CIP of US application with the Serial Number 15/269,444, filed on 09/19/2016, now US Patent 10272035; the 15/439343 is a CIP of US application with the Serial Number 15/269,444, filed on 09/19/2016, now US Patent 10272035; the 15/269,444 is a CIP of US Serial Number 13/457,568, filed on 04/27/2012, now issued US Patent 9,486,357; which is a DIV of US application with the Serial Number 12/985,758, filed on 01/06/2011, now abandoned; which is a CIP of US application with the Serial Number 12/611,682, filed on 11/03/2009, now abandoned; which claims benefit of the provisional application 61/114,143, filed on 11/13/2008.
Upon review of the specifications of the above provisional and non-provisional US applications, and comparison with the specification of the present application it is determined that claims under examination are only entitled to the filing date 11/23/2020 of the present application. This is because there is no written support in any of the prior provisional and non-provisional US applications at least for the specific concept of a method of treating comprising administering to a patient in need thereof a combination of a biocompatible drug and stem cells by at least inhalation, wherein the biocompatible drug comprising one or more cell pathway inhibitors (e.g., elected ROCK inhibitors) and an anti-vascular endothelial growth factor (anti-VEGF) agent together with one or more complement pathway inhibitors (e.g., elected C1 esterase inhibitors) and one or more TGF beta inhibitors, and wherein the administration of the biocompatible drug and the stem cells to the patient treats the one or more neurodegenerative disorders (e.g., elected traumatic brain injury).
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.
Amended claims 1, 4-11, 15 and 17-18 are rejected under 35 U.S.C. 103 as being unpatentable over Wu et al (US 2016/0038408) in view of Kleinschnitz et al (US 9,452,203), Zhou et al (Neuroscience 438:60-69, 2020), Wang et al (US 10,633,393), Roizman et al (WO 2018/161035), Wilson (US 9,241,900) and Peyman (US 2019/0030190). This is a slightly modified rejection necessitated by Applicant’s amendment.
The instant claims encompass a method of treatment, comprising administering (e.g., through the nasal mucosa, through the nasal mucosa olfactory nerve, in the brain or the elected species of by inhalation) to a patient in need thereof a combination of a biocompatible drug and stem cells, the biocompatible drug comprising one or more cell pathway inhibitors (ROCK tr inhibitors as the elected species) and an anti-vascular endothelial growth factor (anti-VEGF) agent together with one or more complement pathway inhibitors (C1 esterase inhibitors as the elected species) and/or one or more TGF beta inhibitors (e.g., botulinum toxin), the patient having one or more neurodegenerative disorders (a traumatic brain injury as the elected species), and the biocompatible drug further comprising nanoparticles or microparticles used as a carrier of the biocompatible drug for sustained release of the biocompatible drug over a time period of at least three months, the biocompatible drug additionally comprising the nanoparticles or microparticles being provided in a solution with a semi-fluorinated alkane, and said administering of the biocompatible drug to the patient results in the semi-fluorinated alkane of the solution evaporating while leaving the nanoparticles or microparticles containing the biocompatible drug on a surface of a tissue of the patient for the sustained release of the biocompatible drug; and wherein the administration of the biocompatible drug and the stem cells treats, alleviates or reduces the symptoms associated with the one or more neurodegenerative disorder.
With respect to the elected species, Wu et al already taught a method for reducing acute axonal injury (AAI which is a traumatic injury to the brain caused by an external force) by intranasally administering to a subject in need thereof an effective amount of a composition that includes one or more compounds that reduce axonal injury after AAI (e.g., GDNF, Neurturin, Artemin and Persephin), and the method further include intranasally administering to the subject neuronal stem cells or adipose-derived stem cells before, during, and/or at the same time as said composition comprising one or more compounds that reduce axonal injury (Abstract; Summary of the Application; particularly paragraphs [0003]-[0004], [0014]-[0018], [0024], [0051], [0055]-[0056], [0069]; Examples; and particularly claims 1,8-12, 19-24). Wu et al also taught that the compound may be associated with a delivery reagent, such as a liposome, micelle, or nanoparticle, and the composition is formulated as an intranasal spray, an intranasal aerosol, or a nasal drop (paragraphs [0018], [0024], [0051], [0055]-[0056]). Wu et al further taught that the composition containing a compound can be formulated to provide a sustained, controlled or delayed release of the active agent using biodegradable polymers such as polylactide-polyglycolide, poly(orthoesters) and poly(anhydrides) (paragraphs [0055]-[0056]). Please note that intranasal drug delivery occurs when particles are inhaled into the nasal cavity and transported directly to the brain, and therefore it is a form of delivery by inhalation.
Wu et al did not teach specifically at least further intranasally administering to the subject in need thereof the combination of drugs that include Rock inhibitors, an anti-VEGF agent, C1 esterase inhibitors and botulinum toxin in the form of nanoparticles for sustained release of the drugs over a time period of at least three months in a solution with semi-fluorinated alkane together with stem cells for reducing acute axonal injury; wherein the administering of the drugs results in the semi-fluorinated alkane in the solution evaporating while leaving the nanoparticles containing the drugs on a surface of tissue of the patient for the sustained release of the drugs; and the same method further comprising a gene therapy using a donor DNA and/or a CRISPR/cas9 complex conjugated with nanoparticles.
Before the filing date of the present application (11/23/2020), Kleinschnitz et al already taught using C1 esterase inhibitor for reducing a secondary brain edema occurring subsequent to an initial injury (e.g., stroke, traumatic brain injury and spinal cord injury), and the C1 inhibitor can be formulated for intranasal administration and such formulation encompasses slow release systems (Abstract; Brief Summary of the Invention; particularly col. 3, last paragraph; col. 4, lines 44-64; col. 8, lines 40-54; col. 10, line 63 continues to line 12 on col. 11; and issued claims 1-30). Kleinschnitz et al also taught that the pharmaceutical composition can include additional compounds that are intended to remove or inhibit blood clot formation in the brain (col. 10, lines 21-28).
Additionally, Zhou et al taught that excessive expression of VEGF is a common cause of blood-brain barrier (BBB) breakdown that triggers severe complications following traumatic brain injury (TBI), and it has been shown that inhibition of VEGF activities may attenuate cerebral edema in pathological conditions (see at least Abstract). Zhou et al demonstrated that VEGI (an anti-VEGF agent) treatment in the early phase of TBI resulted in a marked decrease of BBB permeability, concomitant restoration of normal ratios of VEGF/VEGI and Angpt2/Angpt1, alleviation of edema, decreased neuron cell death and neurological function improvement in a murine traumatic brain injury model (see at least Abstract).
Moreover, Wang et al also taught using a therapeutically effective amount of ROCK inhibitors for treating at least neuronal degeneration, spinal cord injury, Alzheimer’s as well as traumatic brain injury (Abstract; particularly col. 2, line 67 continues to line 24 on col. 3; col. 15, lines 23-31; col. 24, line 45 continues to line 9 on col. 25). Wang et al stated “ROCK inhibitors have been shown to possess anti-inflammatory properties. Thus, they can be used as treatment for neuroinflammatory diseases such as stroke, multiple sclerosis, Alzheimer’s disease…..In addition based on their neurite outgrowth inducing effects, ROCK inhibitors could be useful for neuronal regeneration, inducing new axonal growth and axonal rewiring across lesions with the CNS. ROCK inhibitors are therefore likely to be useful for regenerative (recovery) treatment of CNS disorders such as spinal cord injury, acute neuronal injury (stroke, traumatic brain injury), Parkinson’s disease, Alzheimer’s disease and other neurodegenerative disorders” (col. 2, line 67 continues to line 20 on col. 3). Wang et al taught that disclosed ROCK inhibitor compounds can be formulated for intranasal administration or pulmonary administration, and the formulation may be delivered in the context of a vesicle such as liposome or any other natural or synthetic vesicle (col. 24, line 45 continues to line 9 on col. 25).
Before the filing date of the present application, Roizman et al also taught at least a sustained release composition in the form of nanoparticles or microparticles composed of biodegradable polymer (e.g., lactic acid and/or glycolic acid) and/or hydrogel for delivering one or more therapeutic agents (e.g., anti-dyslipidemic agents, inhibitors of the complement system or components thereof, anti-inflammatory agents and inhibitors of cell migration such as ROCK inhibitors) for the treatment of age-related macular degeneration (AMD) and other eye diseases and disorders, wherein the sustained-release composition releases a low or relative low, but therapeutically effective, dose of one or more therapeutic agents over a period of 3 months, 6 months, 1 year, 1.5 years, 2 years or more (Summary of the Disclosure; particularly paragraphs [0179], [0307], [0310]-[0311] and [0313]-[0314]). Roizman et al stated “Use of a sustained-release composition can have benefits, such as an improved profile of the amount of the drug delivered to the target site over a time period, and improved patient compliance and health due to fewer invasive procedures (e.g., injections into the eye) being performed for administration of the drug” (paragraph [0307]).
Moreover, Wilson already taught a pharmaceutical composition comprising an active ingredient and a non-aqueous, physiologically tolerable, liquid vehicle (a solution) comprising a semi-fluorinated alkane (SFA) (e.g., F4H5 and F6H4) as medicines in ophthalmology (Abstract; Summary of the Invention; col. 5, line 65 continues to line 67 on col. 7; particularly col. 6, lines 39-49; and issued claims 1-21). Wilson also disclosed that SFA is capable of dissolving many poorly water-soluble compounds, well-tolerated by the eye, and suitable as a carrier, vehicle or excipient in ophthalmic compositions for topical or minimally invasive administration (col. 7, lines 14-29).
Furthermore, Peyman also taught at least a method for delivering (e.g., through nasal mucosa for the brain by spraying, drops, or injection to access to olfactory nerves) an opsin family gene to an anatomical or physiological site in a patient in need thereof for stimulating, modifying polarization of, and/or inducing action potential in a cell (e.g., a CNS cell, a spinal cord cell, a glial cell, a stem cell) at the site, the method comprises administering a complex comprising a non-quantum dot nanoparticle carrier (e.g., dendrimers, liposomes, micelles, gold nanoparticles), a biocompatible molecule for cell uptake of the complex (e.g., arginine-cell penetrating peptide, cysteine-cell penetrating peptide), an opsin family gene or another gene with CRISPR/Cas9 RNA, a biocompatible fluid, a ROCK inhibitor which also inhibits TGFβ1/Smad2,3 signal transduction to the anatomical and/or physiological site, to result in formation of light-activated channel in a cell membrane permitting cell stimulation by an external or internal light transmitted by a fiber optic to modify polarization of, and/or induce an action potential in the cell at the site, and counteract an inflammatory response to the tissue to a disease process or conditions (e.g., traumatic brain injury, Alzheimer’s disease, stroke), wherein light-induced cell stimulation may induce cell proliferation which desirably replaces cell loss due to various diseases or conditions (see at least Abstract; Summary; particularly paragraphs [0015]-[0024], [0250]). Peyman taught that the above disclosed gene therapy method can be provided alone or together with additional treatments such as stem cell therapy (e.g., administering cultured stem cells or neuronal stem cells through the nasal mucosa olfactory nerve), and that ROCK inhibitor is administered to a patient to reduce the inflammatory process and facilitate nerve growth in a neurodegenerative disorder (paragraphs [0110]-[0112]). Peyman also taught explicitly that botulinum toxin at low doses or picogram concentration has both an anti-inflammatory effect and anti-TGFβ effect located at the site of Alzheimer plaques, thus reducing the production of Tau entanglement and neurofibrillary elements seen in Alzheimer’s disease plaques or TBI (traumatic brain injury) (paragraph [0341]). Peyman disclosed that CdSe/Au particles are exposed to polyethylene-glycol-(CH2)10-SH to coordinate the thiol to the Au end (paragraph [0055]); and the particles are conjugated to biological active moieties (e.g., DNA, RNA, peptide, protein, antibody) via a covalent bond with an amide, thiol, hydroxyl, carbonyl, sulfo, or other such group on the biologically active moieties (paragraph [0156]). Peyman stated “In general, the nanoparticles, such as gold or graphene, are used as vectors for gene modification as non-homologous end joining or homology directed repair (HDR), where the nanoparticles are coated with cell penetrating agent or a donor DNA and a CRISPR/cas9 guide RNA used along with a thermal energy source that heats up the gold nanoparticles and enhances the cell penetration and endosomal escape while the DNA is not damaged because it is heat resistant as non-homologous end joining or homology directed repair (HDR)” (paragraph [0059]).
Accordingly, before the effective filing date of the present application it would have been obvious and within the scope of skill for an ordinary artisan to modify the teachings of Wu et al by also intranasally administering the drug combination of ROCK inhibitors, C1 esterase inhibitors, VEGI and botulinum toxin in the form of nanoparticles in a solution with semi-fluorinated alkane, that slowly released a low but therapeutically effective dose of one or more therapeutic agents over a period of at least 3 months for the treatment of a patient with acute axonal injury (a TBI), as well as further providing the patient in need thereof a gene therapy using a donor DNA and/or a CRISPR/cas9 complex conjugated with nanoparticles, in light of the teachings of Kleinschnitz et al, Zhou et al, Wang et al, Roizman et al, Wilson and Peyman as presented above.
An ordinary skilled artisan would have been motivated to carry out the above modifications because: (i) Kleinschnitz et al taught using C1 esterase inhibitor in a formulation for intranasal administration to reduce a secondary brain edema occurring subsequent to an initial traumatic brain injury; (ii) Zhou et al demonstrated successfully that VEGI (an anti-VEGF agent) treatment in the early phase of TBI resulted in a marked decrease of BBB permeability, concomitant restoration of normal ratios of VEGF/VEGI and Angpt2/Angpt1, alleviation of edema, decreased neuron cell death and neurological function improvement in a murine traumatic brain injury model; (iii) Wang et al also taught using a therapeutically effective amount of ROCK inhibitors in a formulation for intranasal or pulmonary administration to treat traumatic brain injury in a patient because ROCK inhibitors possess anti-inflammatory properties and neurite outgrowth inducing effects (e.g., inducing new axonal growth and axonal rewiring) that are useful for regenerative treatment of CNS disorders that include traumatic brain injury; (iv) Roizman et al taught a sustained release composition in the form of nanoparticles or microparticles composed of biodegradable polymer such as lactic acid and/or glycolic acid for delivering one or more therapeutic agents (e.g., anti-dyslipidemic agents, inhibitors of the complement system or components thereof, anti-inflammatory agents and inhibitors of cell migration such as ROCK inhibitors) over a period of 3 months, 6 months or more for the treatment of age-related macular degeneration (AMD) and other eye diseases and disorders, and the benefits of using a sustained-release composition such as an improved profile of the amount of the drug delivered to the target site over a time period, and improved patient compliance and health; (v) Wilson already taught at least that semifluorinated alkane is a physiologically tolerable, liquid vehicle (a solution) that is suitable for as a carrier, vehicle or excipient in ophthalmic compositions for topical or minimally invasive administration; and (vi) Peyman already taught delivering a complex comprising a non-quantum dot nanoparticle carrier (e.g., dendrimers, liposomes, micelles, gold nanoparticles), a biocompatible molecule for cell uptake of the complex (e.g., arginine-cell penetrating peptide, cysteine-cell penetrating peptide), an opsin family gene or another gene with CRISPR/Cas9 RNA (including a donor DNA and CRISPR/cas9 guide RNA), a biocompatible fluid, and a ROCK inhibitor to a cell at a physiological site in a patient with a traumatic brain injury via nasal mucosa by spraying, drops, or injection to access to olfactory nerves to counteract inflammatory responses and to induce cell proliferation for cell loss replacement, in combination with a stem cell therapy using cultured stem cells. Moreover, Peyman also taught explicitly that botulinum toxin at low doses or picogram concentration has both an anti-inflammatory effect and anti-TGFβ effect located at the site of Alzheimer plaques, thus reducing the production of Tau entanglement and neurofibrillary elements seen in Alzheimer’s disease plaques or TBI (traumatic brain injury).
An ordinary skilled artisan would have a reasonable expectation of success to carry out the above modification in light of the teachings of Wu et al, Kleinschnitz et al, Zhou et al, Wang et al, Roizman et al, Wilson and Peyman; coupled with the level of skill for an ordinary skilled artisan in the relevant art.
The modified method resulting from the combined teachings of Wu et al, Kleinschnitz et al, Zhou et al, Wang et al, Roizman et al, Wilson and Peyman as set forth above is indistinguishable and encompassed by the presently claimed inventions. With respect to the limitation reciting “said administering of the biocompatible drug to the patient results in the semifluorinated alkane of the solution evaporating while leaving the nanoparticles or microparticles containing the biocompatible on a surface of a tissue of the patient for the sustained release of the biocompatible drug”, since the modified method has the same method step and starting materials, and evaporation is an intrinsic property of the semifluorinated alkane (e.g., F4H5 and F6H4) in the solution; and as a result it leaves the nanoparticles containing the biocompatible drug on a surface of tissue of the patient for the sustained release of the biocompatible drug. Moreover, with respect to dependent claim 15 since the above modified method already comprises the step of intranasally administering of at least ROCK inhibitors together with C1 esterase inhibitors, it would also necessarily result in the production of heat shock proteins.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Claim 12 is rejected under 35 U.S.C. 103 as being unpatentable over Wu et al (US 2016/0038408) in view of Kleinschnitz et al (US 9,452,203), Zhou et al (Neuroscience 438:60-69, 2020), Wang et al (US 10,633,393), Roizman et al (WO 2018/161035), Wilson (US 9,241,900) and Peyman (US 2019/0030190) as applied to claims 1, 4-11, 15 and 17-18 above, and further in view of Blume et al (US 2006/0167110).
The combined teachings of Wu et al, Kleinschnitz et al, Zhou et al, Wang et al, Roizman et al, Wilson and Peyman were presented above. However, none of the cited references teach specifically that the biocompatible drug further comprises low molecular weight heparin and/or heparin mimetics to reduce fibrin formation and an inflammatory process that attracts glial cells stimulation.
Before the filing date of the present application (11/23/2020), Blume et al already taught using heparins or low-molecular-weight heparins as anticoagulants for a second therapeutic agent in a method for reducing neuronal damage associated with cerebrovascular disease such as stroke and cerebral edema (Abstract; particularly paragraphs [0037] and [0084]-[0086]).
Accordingly, before the effective filing date of the present application it would have been obvious and within the scope of skill for an ordinary artisan to further modify the combined teachings of Wu et al, Kleinschnitz et al, Zhou et al, Wang et al, Roizman et al, Wilson and Peyman by also including low-molecular-weight heparins in their drug combination of ROCK inhibitors, C1 esterase inhibitors and botulinum toxin in the form of slow/sustained release nanoparticles to treat a patient with acute axonal injury, in light of the teachings of Blume et al as presented above.
An ordinary skilled artisan would have been motivated to further carry out the above modification because Blume et al already taught using low-molecular-weight heparins as anticoagulants in a method for reducing neuronal damage associated with cerebrovascular disease such as stroke and cerebral edema. Moreover, please note that Kleinschnitz et al already taught using compounds that are intended to remove or inhibit blood clot formation in the brain together with C1 esterase inhibitors for reducing a secondary brain edema occurring subsequent to a trauma brain injury.
An ordinary skilled artisan would have a reasonable expectation of success to carry out the above modification in light of the teachings of Wu et al, Kleinschnitz et al, Zhou et al, Wang et al, Roizman et al, Wilson, Peyman and Blume et al; coupled with the level of skill for an ordinary skilled artisan in the relevant art.
The modified method resulting from the combined teachings of Wu et al, Kleinschnitz et al, Zhou et al, Wang et al, Roizman et al, Wilson, Peyman and Blume et al as set forth above is indistinguishable and encompassed by the presently claimed inventions. With respect to the wherein clause reciting “low molecular weight heparin and/or heparin mimetics to reduce fibrin formation and an inflammatory process that attracts excessive glial cells stimulation”, it is noted that due to the intrinsic anti-coagulant property of the low-molecular-weight heparin, it is cable of reducing fibrin formation as well as reducing inflammatory process that attracts excessive glial cells stimulation.
Therefore, the claimed invention as a whole was prima facie obvious in the absence of evidence to the contrary.
Response to Argument
Applicant’s argument related in part to the above modified 103 rejections in the Amendment filed on 10/20/2025 (pages 9-11) has been fully considered, but it is respectfully not found persuasive for the following reason.
Applicant argued basically that none of the cited references teach or suggest all of the limitations of the currently amended independent claim 1, particularly with the new limitation “the biocompatible drug additionally comprising the nanoparticles or microparticles being provided in a solution with a semifluorinated alkane, and said administering of the biocompatible drug to the patient results in the semifluorinated alkane of the solution evaporating while leaving the nanoparticles or microparticles containing the biocompatible drug on a surface of the patient for the sustained release of the biocompatible drug”. Applicant argued that Examiner relied on the Wilson reference for the teachings of semifluorinated alkanes, however, the reference fails to teach nanoparticles or microparticles being provided in a solution with a semifluorinated alkane. Additionally, Applicant argued that Wu, Kleinschnitz, Zhou, Wang, Roizman and Peyman also fail to remedy the requisite limitation recited in claim 1, particularly the cited combination of references fails to teach that administering of the biocompatible drug to the patients results in the semifluorinated alkane of the solution evaporating while leaving the nanoparticles or microparticles containing the biocompatible drug on a surface of tissue of the patient for the sustained release of the biocompatible drug. With respect to the rejection of claim 12, Applicant argued that Blume also fails to remedy the deficiency of Wu, Kleinschnitz, Zhou, Wang, Roizman, Wilson and Peyman as discussed above.
First, since the above rejection was made under 35 U.S.C. 103 none of the cited references have to teach every limitation of the instant claims. For example, the Wilson reference does not have teach nanoparticles or microparticles being provided in a solution with a semifluorinated alkane, although the reference teaches clearly that semifluorinated alkane is a physiologically tolerable, liquid vehicle (a solution) that is suitable for as a carrier, vehicle or excipient in ophthalmic compositions for topical or minimally invasive administration. It is also apparent that Applicant considered each of the cited references in total isolation one from the others, without taking into consideration of the specific combination of Wu et al, Kleinschnitz et al, Zhou et al, Wang et al, Roizman et al, Wilson and Peyman. Please refer to the above modified 103 rejections for details along with the provided motivations to combine the cited references.
Second, with respect to the limitation reciting “said administering of the biocompatible drug to the patient results in the semifluorinated alkane of the solution evaporating while leaving the nanoparticles or microparticles containing the biocompatible on a surface of a tissue of the patient for the sustained release of the biocompatible drug”, since the modified method has the same method step and starting materials, and evaporation is an intrinsic property of the semifluorinated alkane (e.g., F4H5 and F6H4) in the solution; and as a result it leaves the nanoparticles containing the biocompatible drug on a surface of tissue of the patient for the sustained release of the biocompatible drug. Thus, the combination of the cited references does teach every limitation of the instant claims.
Third, the Blume reference was cited to supplement the combined teachings of Wu et al, Kleinschnitz et al, Zhou et al, Wang et al, Roizman et al, Wilson and Peyman for the limitation recited in dependent claim 12.
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
1. Ryu et al (Journal of Neuroinflammation 5:18; doi:10.1186/1742-2094-5-18, 10 pages, 2008) disclosed VEGF receptor antagonist cyclo-VEGI reduces inflammatory reactivity and vascular leakiness and is neuroprotective against acute excitotoxic striatal insult.
2. Li et al (Clinical Neurology and Neurosurgery 144:7-13, 2016) disclosed the role of vascular endothelial growth factor and vascular endothelial growth inhibitor in clinical outcome of traumatic brain injury.
Conclusion
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Quang Nguyen, Ph.D., at (571) 272-0776.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s SPE, James Douglas (Doug) Schultz, Ph.D., may be reached at (571) 272-0763.
To aid in correlating any papers for this application, all further correspondence regarding this application should be directed to Group Art Unit 1631; Central Fax No. (571) 273-8300.
Any inquiry of a general nature or relating to the status of this application or proceeding should be directed to (571) 272-0547.
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/QUANG NGUYEN/Primary Examiner, Art Unit 1631