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
Claims 48, 49 and 51 are objected to because of the following informalities.
In claim 51, line 3, the word “cyclodextran” is misspelled. In the interest of compact prosecution, the Examiner determines the word to be “cyclodextrin”.
Claims 48 and 49 recite, respectively, that that the “QX-314 comprises a concentration”, and “the TRPV1 modulator comprises a concentration”. A compound cannot comprise a concentration, but can only have a concentration. Accordingly, and consistent with the language of Applicant’s claims 42 and 43, in the interest of compact prosecution the Examiner interprets the claims as directed to, respectively: “cyclodextrin”.
Claims 48 and 49 recite, respectively, that that the “QX-314 has a concentration”, and “the TRPV1 modulator has a concentration”.
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 41, 44 and 47 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.
Claim 44 recites the limitation “wherein the step of administering QX-314 and the TRPV1 modulator results to a subject in need thereof results in preventing sympathetic activation for about 0 to about 60 minutes following the step of administering”. The claim is vague and ambiguous, because 0 minutes amounts to no preventing of sympathetic activation, and is thus contrary to the explicit language of this claim, as well as that of claim 33 from which this claim depends.
Claims 41 and 47 recite the limitation “wherein the TRPV1 modulator is selected from . . . change in temperature or pH”. This renders the claims vague and indefinite because in contrast to the rest of the claims, which recite specific compounds, change in temperature or pH is not a TRPV1 modulator. Even assuming, arguendo, that a change in temperature or pH could modulate TRPV1, these factors are not considered a “modulator” per se. Moreover, the claims as presented are directed to any and every temperature or pH, and not specific ones, which may potentially have a role in modulating TRPV1.
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 33-51 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”).
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]).
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]).
Regarding claims 45, 50 and 51, 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])).
Regarding claim 46, Bean discloses the composition of claim 45, wherein the composition comprises a mixture of QX-314 and the TRPV1 modulator (combination of capsaicin and QX-314 ([0193]).
Regarding claim 47, Bean discloses the composition of claim 20, 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 claims 42 and 48, Bean discloses QX-314 of 5 mM. ([0202]).
Per Applicant’s claims 43 and 49, Bean discloses capsaicin (TRPV1 modulator) of 500 nm or 1 mM, which converts to 0.152705 mg/ml or 0.30541 mg/ml. ([0202]).1
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).
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.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SVETLANA M IVANOVA/Primary Examiner, Art Unit 1627
1 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