Ex Parte PeymanDownload PDFPatent Trial and Appeal BoardDec 20, 201714160174 (P.T.A.B. Dec. 20, 2017) Copy Citation United States Patent and Trademark Office UNITED STATES DEPARTMENT OF COMMERCE United States Patent and Trademark Office Address: COMMISSIONER FOR PATENTS P.O.Box 1450 Alexandria, Virginia 22313-1450 www.uspto.gov APPLICATION NO. FILING DATE FIRST NAMED INVENTOR ATTORNEY DOCKET NO. CONFIRMATION NO. 075200.46 4526 EXAMINER POPA, ILEANA ART UNIT PAPER NUMBER 1633 MAIL DATE DELIVERY MODE 14/160,174 01/21/2014 Gholam A. Peyman 13010 7590 12/21/2017 The Law Office of Patrick F. 0"Reilly III, LLC 1509 Lafayette Drive Columbus, OH 43220-3869 12/21/2017 PAPER Please find below and/or attached an Office communication concerning this application or proceeding. The time period for reply, if any, is set in the attached communication. PTOL-90A (Rev. 04/07) -UNITED STATES PATENT AND TRADEMARK OFFICE BEFORE THE PATENT TRIAL AND APPEAL BOARD Ex parte GHOLAM A. PEYMAN1 Appeal 2017-010738 Application 14/160,174 Technology Center 1600 Before JEFFREY N. FREDMAN, JOHN G. NEW, and JOHN E. SCHNEIDER, Administrative Patent Judges. NEW, Administrative Patent Judge. DECISION ON APPEAL appellant states that the real party-in-interest is the named inventor, Gholam A. Peyman. App. Br. 2. Appeal 2017-010738 Application 14/160,174 SUMMARY Appellant files this appeal under 35 U.S.C. § 134(a) from the Examiner’s Non-Final Rejection of claims 1, 2, 4, 5, 9, 11—17, 19, and 22— 28. Specifically, claims 1, 2, 5, 9, 11, and 13—16 stand rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of Olson et al (US 2011/0270153 Al, November 3, 2011) (“Olson”), Klapoetke et al. (US 2014/0324134 Al, October 30, 2014) (“Klapoetke”), J. Zhang et al., Integrated Device for Optical Stimulation and Spatiotemporal Electrical Recording of Neural Activity in Light-Sensitized Brain Tissue, 6(5) J. Neural. Eng. 1—24 (2009) (“Zhang”), and D.K. James et al., Graphene: Powder, Flakes, Ribbons, and Sheets, 46 Accts. Chem. Res., 2307-18 (2012) (“James”). Claims 1, 2, 5, 9, 11—16, 19, 22, 23, and 25—28 stand rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of Olson, Klapoetke, Zhang, James, and P. Li et al., A Wireless Power Interface for Rechargeable Battery Operated Neural Recording Implants, Proc. 28th IEEE EMBS Ann. Int’l Conf. 6253-56 (2006) (“Li”). Claims 1, 2, 5, 9, 11—17, 19, and 22—28 stand rejected as unpatentable rejected under 35 U.S.C. § 103(a) as being obvious over the combination of Olson, Klapoetke, Zhang, James, Li, and M. Mogi et al., Brain-Derived Growth Factor and Nerve Growth Factor Concentrations are Decreased in the Substantia Nigra in Parkinson’s Disease, 270 Neurosci. Lett., 45—48 (1999) (“Mogi”). Claims 1, 2, 4, 5, 9, 11, and 13—16 stand rejected as unpatentable under 35 U.S.C. § 103(a) as being obvious over the combination of Olson, 2 Appeal 2017-010738 Application 14/160,174 Klapoetke, Zhang, Janies, and J.D. Heiss et al., Image-Guided Convection- Enhanced Delivery of Muscimol to the Primate Brain, 112 J. Neurosurg., 1-13 (2010). We have jurisdiction under 35 U.S.C. § 6(b). We REVERSE. NATURE OF THE CLAIMED INVENTION Appellant’s invention is directed to methods and compositions to controllably regulate cells at a target site. A quantum dot-targeting agent and ion channel gene complex is administered and the complex is stimulated using an implanted fiber optic system. Abstract. REPRESENTATIVE CLAIM Claim 1 is representative of the claims on appeal and recites: 1. A method to enhance functional recovery of a cell in a patient in need thereof, the method comprising: administering to a patient in need thereof, in or with a biocompatible fluid, a plurality of nanoparticles selected from the group consisting of graphene quantum dots, graphene-oxide quantum dots, graphene-zinc oxide quantum dots, quantum dots with at least one (poly)ethylene glycol (PEGylated) quantum dot, graphene nanotubes, carbon nanotubes, and combinations thereof, where the nanoparticles are coated with a biocompatible molecule for cell uptake, contain an antibody that targets the nanoparticles to a cell, and a gene selected from the group consisting of a rhodopsin gene, a channelrhodopsin gene, a halorhodopsin gene, and combinations thereof, one or more of the nanoparticles functioning as a carrier of the gene to the cell, and are injected with a biocompatible fluid for, without reliance on a viral vector, building a light activated rhodopsin channel in 3 Appeal 2017-010738 Application 14/160,174 a membrane of a cell having a defective or absent gene selected from the group consisting of a rhodopsin gene, a channelrhodopsin gene, a halorhodopsin gene, and combinations thereof so that the cell can be stimulated by an external or internal light transmitted by a fiber optic device comprising a fiber optic tip containing a light source, the fiber optic device further comprising an electrical sensor including a plurality of graphene ribbons spaced apart on a surf ace of the fiber optic tip, and a controller to receive and generate electrical signals resulting from the altered cellular electrical property at the site, the controller being operatively connected to the plurality of graphene ribbons of the electrical sensor, the controller receiving feedback from the plurality of graphene ribbons of the electrical sensor, and providing the signals to a processor to monitor and/or controllably alter the light activated nanoparticles and the rhodopsin membrane channel using the controller. App. Br. 17. ISSUES AND ANALYSES We do not agree with, and decline to adopt, the Examiner’s findings of fact and prima facie conclusions that the appealed claims are obvious over the cited prior art. We address the dispositive arguments raised by Appellant below. A. Claims E 2, 5, 9, 11, and 13—16 Issue 4 Appeal 2017-010738 Application 14/160,174 Appellant argues the Examiner erred because the combined cited prior art neither teaches nor suggests the limitation of claim 1 reciting: “one or more of the nanoparticles functioning] as a carrier of the gene to the cell.” App. Br. 6. Analysis The Examiner finds, inter alia, that Olson teaches a method comprising injecting quantum dots (“QDs”) directly into damaged neural tissue and activating the QDs with electromagnetic radiation to electrically stimulate the neurons via the electrical energy discharged by the activated QDs. Final Act. 3^4 (citing Olson H 11—17, 38, 55—58). The Examiner finds that teaches that QDs comprise biocompatible PEG-lipids and coupling QDs with antibodies for targeting cells at the desired site. Id. at 4 (citing Olson 144; claims 1,5,11, and 14—16). However, the Examiner finds Olson neither teaches nor suggests an expression plasmid encoding rhodopsin. Id. The Examiner finds that Klapoetke teaches a method of treating a disease, such as Parkinson’s disease, by modifying the membrane potential of cells by administering an expression plasmid encoding channelrhodopsin to subjects and activating the expressed rhodopsin by light. Final Act. 4 (citing Klapoetke 119-11, 64, 87, 100, 118, 119, 127, 135-137, 170). The Examiner concludes that it would have been obvious to skill in a person of ordinary skill the art to associate the expression plasmid of Klapoetke with the QDs of Olson to achieve the predictable result of obtaining a composition suitable to treat Parkinson’s disease. Id. (citing In re Kerkhoven, 626 F.2d 846, 850 (C.C.P.A. 1980)). 5 Appeal 2017-010738 Application 14/160,174 Appellant argues that the references fail to teach the limitation of claim 1 reciting: “one or more nanoparticles functioning as a carrier of the gene to the cell.” App. Br. 6. Appellant asserts that the Olson reference does not teach gene therapy at all, but, rather, Olson is instead directed to cell stimulation using quantum dots. Id. (citing Olson Abstr.). Appellant argues that the Examiner therefore cites to Klapoetke to remedy the alleged deficiencies of Olson. Id. (citing Final Act. 4). However, Appellant contends that, even assuming arguendo that one of ordinary skill in the art would combine the teachings of Klapoetke with those of Olson (the which contention Appellant rejects), a person of ordinary skill in the art would nevertheless fail to arrive at the claimed invention because Klapoetke teaches the use of a viral or expression plasmid as a carrier for the genes, and not the nanoparticles specified by claim 1. Id. As such, Appellant argues, because Klapoetke teaches a different type of carrier for the described genes, and is silent with respect to quantum dots, a person of ordinary skill in the art would not be led to use the specific types of nanoparticles required by claim 1 as gene carriers. Id. Moreover, Appellant argues, the Examiner relies upon Zhang and James only for features related to the claimed fiber optic device, and therefore these references fail to remedy the alleged deficiencies of Olson and Klapoetke with respect to the disputed limitations. Id. (citing Final Act. 5-6). The Examiner responds that the rejection is based is based, in part, on combining the QDs taught by Olson with a channelrhodopsin-expressing plasmid, as taught by Klapoetke into a single composition by coupling the plasmid to the QDs; two compositions both being useful for the same 6 Appeal 2017-010738 Application 14/160,174 purpose (e.g., the treatment of Parkinson’s disease). Ans. 10. The Examiner points out that Appellant does not argue that a person of ordinary skill in the art would not have been capable of combining the teachings of the references. Id. The Examiner finds that, by coupling the channelrhodopsin expression plasmid with the QDs, one of skill in the art would have been able to use the QDs as a carrier for the expression plasmid and, therefore, also for the channelrhodopsin gene encoded by the expression plasmid, as required by the instant claim 1. Id. The Examiner emphasizes that that Appellant’s claims on appeal do not exclude an embodiment in which the channelrhodopsin gene is part of a plasmid. Id. at 10-11. We are not persuaded that the Examiner has established a prima facie case of obviousness with respect to this limitation of the claim. Olson is directed to: “methods for stimulating cells using quantum dots.” Olson Abstr. Specifically, Olson teaches that: [S]uch methods include placing a composition comprising a quantum dot within a location sufficient to cause the neural cell function to be stimulated by electrical energy produced by the quantum dot; and irradiating the composition with electromagnetic radiation comprising a wavelength that is absorbed by the quantum dot and is reemitted as an electrical energy that sufficiently stimulates the neural cell function to treat the clinical condition. Olson || 11—13. Furthermore, Olson teaches that its quantum dots can have a: coating, formed of, for example, PEG lipids or other suitable material; and biofimctional material, formed of, for example, biotin, streptavadin, adhesion proteins, vitamins, organic an inorganic compounds, carbohydrates, aptamers, amino acids, 7 Appeal 2017-010738 Application 14/160,174 lipids, hyaluronic acid, or other suitable proteins. Such proteins would include, but not limited to, individual amino acids, small peptides, antibodies including human, animal, humanized, monoclonal, and chimeric antibodies used to target various cells and cellular structures, as well as the various classes of antibodies such as IgG, IgM, IgA, IgM, and IgD. The quantum dots could further be conjugated with one another in various combinations, as well as with the proteins, peptides, and amino- acids, and other compounds listed above. Olson 144. However, Olson contains no teaching or suggestion concerning conjugating an expressible nucleic acid or gene, either alone or in conjugation with a viral vector, to a quantum dot, or the quantum dot “functioning as a carrier of the gene to the cell,” as required by claim 1. Klapoetke “relates to isolated light-activated ion channel polypeptides [e.g., channelrhodopsin] and methods for their preparation and use. The invention also includes isolated nucleic acid sequences that encode light- driven ion channels of the invention as well as vectors and [] constructs that comprise such nucleic acid sequences.” Klapoetke 1 6. Klapoetke teaches: Some embodiments of the invention include ... a vector that contains the gene for the light-activated ion channel polypeptide. As used herein, the term “vector” refers to a nucleic acid molecule capable of transporting between different genetic environments another nucleic acid to which it has been operatively linked. The term “vector” also refers to a virus or organism that is capable of transporting the nucleic acid molecule. One type of vector is an episome, i.e., a nucleic acid molecule capable of extra-chromosomal replication. Some useful vectors are those capable of autonomous replication and/or expression of nucleic acids to which they are linked. Vectors capable of directing the expression of genes to which they are operatively linked are referred to herein as “expression vectors”. 8 Appeal 2017-010738 Application 14/160,174 Other useful vectors, include, but are not limited to viruses such as lentiviruses, retroviruses, adenoviruses, and phages. Klapoetke 86—87. Klapoetke thus teaches delivery of genes encoding channelrhodopsin via various viral vectors, but the Examiner points to no teaching or suggestion, nor can we discern one, concerning the employment of quantum dots or other semiconductor nanoparticles as a means for directly delivering such genes to cells. Simply put, there is no nexus between the teachings of Olson and Klapoetke that would lead a person of ordinary skill in the art to understand that quantum dots can be used as a carrier of a gene encoding channelrhodopsin for delivery to a cell, as expressly recited in the claim. The remaining references, Zhang and James are not cited by the Examiner as being directed to this limitation, and we therefore reverse the Examiner’s rejection of the claim 1. Moreover, because claims 2, 4, 5, 9, 11, and 13—17 depend, directly or indirectly, from claim 1, we similarly reverse the Examiner’s rejection of those claims. B. Claims 19 and 22—28 Issue Appellant argues that the Examiner erred in finding the combined cited prior art teaches or suggests the limitation reciting: “the electrical sensor of the fiber optic device including a plurality of graphene ribbons spaced apart on a surface of at least a portion of the fiber optic, the plurality of graphene ribbons of the electrical sensor terminating at different distances from a tip of the fiber optic at the site” and “using the plurality of graphene 9 Appeal 2017-010738 Application 14/160,174 ribbons as transistors for providing feedback to the [fiber optic device] controller.” App. Br. 9.2 Analysis The Examiner finds Zhang teaches that a dual-function optrode can supply electromagnetic radiation capable of controlled light delivery to neurons and recording electrical signals. Final Act. 5. The Examiner finds Zhang teaches the optrode comprises a fiber optic having a tip associated with a metallic layer coupled to a wire serving as electrical conduit (i.e., a sensor). Id. The Examiner further finds that Zhang teaches that an LED could be used as the light source to activate rhodopsin. Id. (citing Zhang 2, 10—11, Fig. 1). The Examiner concludes that a person of ordinary skill in the art would have found obvious to modify the methods of Olson and 2 We note that claim 1 similarly recites: [A] fiber optic device comprising a fiber optic tip containing a light source, the fiber optic device further comprising an electrical sensor including a plurality of graphene ribbons spaced apart on a surf ace of the fiber optic tip, and a controller to receive and generate electrical signals resulting from the altered cellular electrical property at the site, the controller being operatively connected to the plurality of graphene ribbons of the electrical sensor, the controller receiving feedback from the plurality of graphene ribbons of the electrical sensor, and providing the signals to a processor to monitor and/or controllably alter the light activated nanoparticles and the rhodopsin membrane channel using the controller. Our reasoning explained herein with respect to claims 19 and 22—28, therefore, applies similarly to claim 1 and its dependents. 10 Appeal 2017-010738 Application 14/160,174 Klapoetke further implanting a device comprising a dual optrode connected to a programmable stimulator adapted to control the light exposure time and/or intensity from an LED source to achieve the predictable result of activating the complex of QDs and channelrhodopsins according to the evolution of symptoms. Id. The Examiner further finds that graphene ribbons were known in the prior art as being electrically conductive. Final Act. 5 (citing James Abstr.). The Examiner concludes that it would have been obvious to a person of ordinary skill in the art, at the effective filing date of the invention, to modify the method taught by the combination of the cited prior art by using a plurality of graphene ribbons as sensors for their optrode located at different distance from the tip and further operably connecting the graphene ribbons to the controller to achieve the predictable result of obtaining dual function optrode capable of controlled light delivery to neurons and recording electrical signals. Id. at 5—6. We are not persuaded by the Examiner’s findings and conclusions. Zhang teaches: The single optrode is a tapered glass optical fiber with a sub micron-sized aperture at its tip formed by gold metallization cladding.... A magnet wire (Alpha Wire Company) was attached to the metalized part of the optrode by means of silver epoxy (H20E; Epoxy Technology) and served as the electrical conduit to external recording electronics. With the exception of the final 50 pm of the tapered tip, the metalized part of the fiber was insulated using a UV-curable epoxy (Norland Optical Adhesive 74). Zhang 3; see also Fig. 1. Furthermore, Zhang expressly teaches that the exposed gold cladding at the tip of the optrode is used for recording 11 Appeal 2017-010738 Application 14/160,174 extracellular neuronal activity: specifically, in the example cited by Zhang, for recording the activity of retinal cells: An optrode, mounted on a 3D micromanipulator, was inserted into the retina until spikes were detected. The extracellular potential from the optrode (i.e., recorded by its conductive cladding), with reference to a[n] Ag/AgCl wire in the bath, was preamplified (1000 gain, 1—10 kHz bandpass; Low Noise Preamplifer Iso-DAM8, World Precision Instruments). Raw data (10 kHz sampling rate) were then acquired using Lab view (National Instruments™). All the spikes were thresholded at - 300 gV (250 Hz-4.8 kHz) and overlaid in a 2 ms window using Matlab. The spike rasters were obtained using a Matlab program as well. Zhang 5; see also Fig. 3. In the other examples cited in Zhang, the optrode is used to provide a light source in the stimulation of locally patch-clamped channelrhodopsin (ChR2)-expressing pyramidal cells and as part of a multielectrode array. Zhang 7—8. Zhang offers no teaching or suggestion about using the conducting elements (i.e., the gold cladding and the attached magnet wire) of the optrode as “transistors for providing feedback to the [fiber optic device] controller,” as recited in claim 19. Furthermore, the exposed conducting element, the gold cladding at the exposed tip of the electrode, is circumferential around the optical aperture tip and does not constitute, as required by the claim, “electrical sensor[s] terminating at different distances from a tip of the fiber optic at the site.” Zhang 3, Fig. 1. Rather, the gold acts as a low-impedance recording electrode for measuring local neural action potential activity. Zhang Fig. 3. James is directed to graphene ribbons, and teaches that they can be used as electrodes. See James Abstr. But James offers no teaching or suggestion that a “plurality of graphene ribbons of the electrical sensor 12 Appeal 2017-010738 Application 14/160,174 terminate] at different distances from a tip of the fiber optic at the site” are “connected] ... a controller” and act to “sens[e] an electrical signal using the plurality of graphene ribbons as transistors for providing feedback to the controller.” The Examiner suggests that it would have been obvious to a person of ordinary skill in the art to substitute the wire of Zhang with the graphene ribbons of James (see Ans. 13) but this is not persuasive evidence of obviousness because, as we have explained, the magnet wire of Zhang is used to connect the gold cladding recording electrode of the optrode to the recording elements and is not acting as a transistor for the feedback control of the fiber optic light source controller of the optrode. In summary, we are not persuaded by the Examiner’s findings that the combination of Zhang, James, and the other cited prior art teach or suggest the disputed limitations. We consequently reverse the Examiner’s rejection of the claims. DECISION The Examiner’s rejection of claims 1, 2, 4, 5, 9, 11—17, 19, and 22—28 as unpatentable under 35 U.S.C. § 103(a) is reversed. REVERSED 13 Copy with citationCopy as parenthetical citation