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 .
Claim Objections
In view of Applicant’s cancellations of the objected to claims, the objections are hereby withdrawn.
Claim Rejections - 35 USC § 112
In view of Applicant’s amendment of claim 41, and cancellation of claim 47, the rejection over these claims is withdrawn.
Applicant’s claim amendments and arguments concerning claim 41 have been considered, but are not found to be persuasive. Claim 41 recites the limitation “wherein the TRPV1 modulator is selected from . . . a compound or an environmental factor that results in change in temperature or pH”. This renders the claims vague and indefinite because the claimed compound is defined by what it does, and not what it is, and thus encompasses an indeterminate number of compounds, to include ones, which have not been described yet. Further, neither the claims, nor the Specification, provide any guidance on what specific pH or temperature cause TRPV1 modulation.
Applicant has argued that it was known that TRPV1 may be modulated by changes in temperature and pH, citing to:
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It is noted in response that neither of the references were provided and cited in an IDS, and have not been made properly of record available for review. Applicant is requested to make the references of record, and instead of making a blanket statement, to provide a detailed explanation instead of what portions of the references it is relying on, and how they support the scope of its claims. Brauchi, as evidenced from the title, relates to TRPM8, not TRMP1. To the extent that the Examiner obtained for the record a google copy of the Abstract1 in Caterina, as another example, it relates to the TRP family of ion channels broadly, not TRPV1 receptor specifically. Further, the disclosure provides that “cloned capsaicin receptor is also activated by increases in temperature in the noxious range”. Applicant’s claims are not limited to any change in temperature (in the noxious range, etc.). The Specification provides none either. The only guidance in the Specification pertaining to this claim language is as short, and as broad and vague, as the very language of the claim.
Claim Rejections - 35 USC § 102
Applicant’s arguments have been carefully considered, but have not been found to be persuasive. Applicant has argued the following:
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In response, the rejection has been updated with a Claim interpretation section, which provides further guidance, based on the Specification, how Bean meets Applicant’s claim limitations.
Claim interpretation
Applicant’s claim 33 is directed to a method of co-administering QX-314 and a TRPV1 modulator to prevent sympathetic activation resulting from administration of a TRPV1 modulator alone comprising administering QX-314 and the TRPV1 modulator to a subject in need thereof.
The Specification provides the following guidance as to who a patient in need of preventing sympathetic activation. It is noted that the method includes, inter alia, patients to whom the administering is being done for treating pain.
[0029] In some embodiments, the methods disclosed herein are used to treat acute or chronic cardiovascular disease, acute or chronic pain, acute or chronic lung disease such as chronic asthma or obstructive pulmonary disease, acute or chronic arthritis, acute or chronic radiculopathy, hypertension, myocardial infarction, arrhythmias, heart failure, or other conditions for which chronic inflammation is an important pathophysiologic factor and neural desensitization is desired. (emphasis added).
Rejection
Regarding claims 33, 37, 38 and 41, Bean discloses a method of co-administering QX-314 and a TRPV1 modulator to prevent sympathetic activation resulting from administration of a TRPV1 modulator alone (a method for treating pain ...administering to the patient a first compound that activates a membrane bound receptor/ion channel through which a second compound can pass, wherein the second compound inhibits one or more voltage-gated ion channels. See, cf.:
-[a]ctivators of TRPV1 receptors include but are not limited to capsaicin ([0012]);
-the second compound inhibits voltage-gated sodium channels. Exemplary inhibitors of this class are QX-314 ([0014]);
-injection of a combination of capsaicin, QX-314, and lidocaine provides robust analgesia, including blockade of the acute pain-evoking response elicited by capsaicin alone ([0018]);
-comprising administering QX-314 and the TRPV1 modulator to a subject in need thereof (injection of a combination of capsaicin, QX-314, and lidocaine provides robust analgesia, including blockade of the acute pain-evoking response elicited by capsaicin alone ([0071]);
-the topical vehicle containing the combination of the invention is preferably applied to the site of discomfort on the subject ([0137]).
In accordance with paragraph [0029] of Applicant’s specification (see Claim interpretation section), this disclosure meets Applicant’s definition for a method of co-administering QX-314 and a TRPV1 modulator to prevent sympathetic activation resulting from administration of a TRPV1 modulator alone comprising administering QX-314 and the TRPV1 modulator to a subject in need thereof. Stated otherwise, since the administering of same combination is being done to a patient with an encompassed condition, per Applicant’s own Specification, it will result in the same preventing sympathetic activation, as per Applicant’s claims.
Claims 33-43 are pending, and have been examined herewith.
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.
Claim 41 is 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.
Claim 41 recites the limitation “wherein the TRPV1 modulator is selected from . . . a compound or an environmental factor that results in change in temperature or pH”. This renders the claims vague and indefinite because the claimed compound is defined by what it does, and not what it is, and thus encompasses an indeterminate number of compounds, to include ones, which have not been described yet. Further, neither the claims, nor the Specification, provide any guidance on what specific pH or termper
Applicant has argued that it was known that TRPV1 may be modulated by changes in temperature and pH, citing to:
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It is noted in response that neither of the references were provided and cited in an IDS, and have not been made properly of record available for review. Applicant is requested to make the references of record, and instead of making a blanket statement, to provide a detailed explanation instead of what portions of the references it is relying on, and how they support the scope of its claims. Brauchi, as evidenced from the title, relates to TRPM8, not TRMP1. To the extent that the Examiner obtained for the record a google copy of the Abstract2 in Caterina, as another example, it relates to the TRP family of ion channels broadly, not TRPV1 receptor specifically. Further, the disclosure provides that “cloned capsaicin receptor is also activated by increases in temperature in the noxious range”. Applicant’s claims are not limited to any change in temperature (in the noxious range, etc.). The Specification provides none either. The only disclosure in the Specification pertaining to this claim language is as short and as broad and vague as the very language of the claim.
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.
(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 33-44 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by US 20110086818 to Bean et al. ("Bean”, of record).
Claim interpretation
Applicant’s claim 33 is directed to a method of co-administering QX-314 and a TRPV1 modulator to prevent sympathetic activation resulting from administration of a TRPV1 modulator alone comprising administering QX-314 and the TRPV1 modulator to a subject in need thereof.
The Specification provides the following guidance as to who a patient in need of preventing sympathetic activation. It is noted that the method includes, inter alia, patients to whom the administering is being done for treating pain.
[0029] In some embodiments, the methods disclosed herein are used to treat acute or chronic cardiovascular disease, acute or chronic pain, acute or chronic lung disease such as chronic asthma or obstructive pulmonary disease, acute or chronic arthritis, acute or chronic radiculopathy, hypertension, myocardial infarction, arrhythmias, heart failure, or other conditions for which chronic inflammation is an important pathophysiologic factor and neural desensitization is desired. (emphasis added).
Rejection
Regarding claims 33, 37, 38 and 41, Bean discloses a method of co-administering QX-314 and a TRPV1 modulator to prevent sympathetic activation resulting from administration of a TRPV1 modulator alone (a method for treating pain ...administering to the patient a first compound that activates a membrane bound receptor/ion channel through which a second compound can pass, wherein the second compound inhibits one or more voltage-gated ion channels. See, cf.:
-[a]ctivators of TRPV1 receptors include but are not limited to capsaicin ([0012]);
-the second compound inhibits voltage-gated sodium channels. Exemplary inhibitors of this class are QX-314 ([0014]);
-injection of a combination of capsaicin, QX-314, and lidocaine provides robust analgesia, including blockade of the acute pain-evoking response elicited by capsaicin alone ([0018]);
-comprising administering QX-314 and the TRPV1 modulator to a subject in need thereof (injection of a combination of capsaicin, QX-314, and lidocaine provides robust analgesia, including blockade of the acute pain-evoking response elicited by capsaicin alone ([0071]);
-the topical vehicle containing the combination of the invention is preferably applied to the site of discomfort on the subject ([0137]).
In accordance with paragraph [0029] of Applicant’s specification (see Claim interpretation section), this disclosure meets Applicant’s definition for a method of co-administering QX-314 and a TRPV1 modulator to prevent sympathetic activation resulting from administration of a TRPV1 modulator alone comprising administering QX-314 and the TRPV1 modulator to a subject in need thereof. Stated otherwise, since the administering of same combination is being done to a patient with an encompassed condition, per Applicant’s own Specification, it will result in the same preventing sympathetic activation, as per Applicant’s claims.
Regarding claim 34, Bean discloses the method of claim 1, wherein QX-314 is administered before the TRPV1 modulator (QX-314 injected 10 minutes before capsaicin ([0067]).
Regarding claim 35, Bean discloses the method of claim 1, wherein QX-314 and the TRPV1 modulator are administered at the same time (application of lidocaine, a membrane permeable sodium channel inhibitor, with QX-314 and capsaicin [(0070)).
Regarding claim 36, Bean discloses the method of claim 1, wherein QX-314 is administered after the TRPV1 modulator ([capsaicin activates the TRPV1 channel receptor and allows QX-314 to pass into the intracellular space through this activated receptor channel. Once in the intracellular space, QX-314 can inhibit sodium voltage-gated channels, thereby providing a reduction or elimination of pain ([0210)]).
Regarding claims 38-40, Bean discloses the method of claim 1, wherein administering QX-314 and TRPV 1 modulator comprises administration by two different methods of administration, or the same method of administration (e.g., administration of a combination of the invention may be by any suitable means that results in the reduction of pain sensation at the target region ...e.g., topical, ([0123], vascular [0018]).
Bean discloses a composition to prevent sympathetic activation (composition with a pharmaceutically acceptable excipient, such as saline /NaCl ([0023-4], [0204], claim 32); provides robust analgesia, including blockade of the acute pain-evoking response ([0071]) comprising QX-314 and a TRPV1 modulator (a method for treating pain ...administering to the patient a first compound that activates a membrane bound receptor/ion channel through which a second compound can pass, wherein the second compound inhibits one or more voltage-gated ion channels ([0012]); [a]ctivators of TRPV1 receptors include but are not limited to capsaicin ([0014]); the second compound inhibits voltage-gated sodium channels. Exemplary inhibitors of this class are QX-314 ([0018])).
Bean discloses wherein the composition comprises a mixture of QX-314 and the TRPV1 modulator (combination of capsaicin and QX-314 ([0193]). Bean discloses wherein the TRPV1 modulator is capsaicin (combination of capsaicin and QX-314 ([0193]); [a]ctivators of TRPV1 receptors include but are not limited to capsaicin ([0014])). Per Applicant’s claim 42, Bean discloses QX-314 of 5 mM. ([0202]). Per Applicant’s claim 43, Bean discloses capsaicin (TRPV1 modulator) of 500 nm or 1 mM, which converts to 0.152705 mg/ml or 0.30541 mg/ml. ([0202]).3
Per Applicant’s claim 44, Bean discloses that the step of administration of QX-314 and the TRPV1 modulator results in preventing sympathetic activation for about 0 to about 60 minutes following the step of administering. (Fig. 1C- from 1 to 25 minutes).
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 SVETLANA M IVANOVA whose telephone number is (571)270-3277. The examiner can normally be reached 8:30-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney L. Klinkel can be reached at (571) 270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SVETLANA M IVANOVA/Primary Examiner, Art Unit 1627
1 “Capsaicin, the main pungent ingredient in 'hot' chilli peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system. We have used an expression cloning strategy based on calcium influx to isolate a functional cDNA encoding a capsaicin receptor from sensory neurons. This receptor is a non-selective cation channel that is structurally related to members of the TRP family of ion channels. The cloned capsaicin receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo.”
2 “Capsaicin, the main pungent ingredient in 'hot' chilli peppers, elicits a sensation of burning pain by selectively activating sensory neurons that convey information about noxious stimuli to the central nervous system. We have used an expression cloning strategy based on calcium influx to isolate a functional cDNA encoding a capsaicin receptor from sensory neurons. This receptor is a non-selective cation channel that is structurally related to members of the TRP family of ion channels. The cloned capsaicin receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo.”
3 To convert 500 nM of capsaicin to mg/mL. The molecular weight of capsaicin is 305.41 g/mol.
1 nM = 0.001 µM. Therefore, 500 nM = 500 * 0.001 µM = 0.5 µM
The formula to convert from µM to µg/mL is: µg/mL = µM * (MW in KD). Since the molecular weight is in g/mol, use the equivalent relationship:
µg/mL = µM * (MW in g/mol) / 1000 (because 1 g = 1000 mg = 1,000,000 µg, and 1 L = 1000 mL)
µg/mL = 0.5 µM * 305.41 g/mol / 1000
µg/mL = 0.152705 µg/mL
Therefore, 500 nM of capsaicin equals 0.152705 µg /mL
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