DETAILED ACTION
Election/Restrictions
Applicants’ election without traverse of Group II, claims 2 and 4-17, in the reply filed on 6/5/26 is acknowledged.
Claim Rejections - 35 USC § 112-2nd paragraph
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 2 and 4-17 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 2:
A method of suppressing visceral pain in a patient, the method comprising: a. identifying an organ in the patient that is causing the visceral pain;
b. mapping the organ to a specific dermatome nerve according to the following instructions, thereby matching said organ to one or more specifically designated dermatome nerve(s):
i. urinary bladder maps to the T11, T12, L1, S1, S2, S3 and/or S4 dermatome nerve(s);
ii. fallopian tube(s) maps to the T11 dermatome nerve(s);
iii. uterus maps to the T12 and/or L1 dermatome nerve(s);
iv. cervix maps to the S2, S3 and/or S4 dermatome nerve(s);
V. stomach maps to the T8, T9 and/or T10 dermatome nerve(s);
vi. liver maps to the T8, T9, T10 and/or T11 dermatome nerve(s);
vii. gall bladder maps to the T8, T9, T10 and/or T11 dermatome nerve(s);
viii. pancreas maps to the T7, T8, T9, T10, T11 and/or T12 dermatome nerve(s);
ix. small intestine maps to the T10, T11 and/or T12 dermatome nerve(s);
X. colon maps to the T11, S1, S2, S3 and/or S4 dermatome nerve(s);
xi. kidney maps to the T10, T11, T12 and/or L1 dermatome nerve(s);
xii. ureter maps to the T11, T12 and/or L1 dermatome nerve(s);
xiii. ovary maps to the T11 dermatome nerve(s);
xiv. testes maps to the T10, T11, L1, L2, S1, S2, S3 and/or S4 dermatome nerve(s);
xv. epididymis maps to the T10, T11, L1, L2, S1, S2, S3 and/or S4 dermatome nerve(s); thereby matching the organ to the one or more specifically designated dermatome nerve(s); and
c. administering a therapeutically effective amount of [any] clostridial neurotoxin at a site proximal to the one or more specifically designated dermatome nerve(s), wherein following administration of the clostridial neurotoxin to the patient, the clostridial neurotoxin is transported via retrograde axonal transport to the spinal cord where it binds sensory afferent nerve cells, enters said cells by receptor- mediated endocytosis and suppresses neurotransmitter release therefrom, thereby suppressing said visceral pain, wherein the clostridial neurotoxin is administered by intradermal administration.
Is vague and indefinite because it is unclear what “instructions” the claim is referring to. Is this a separate instruction manual? What are the instructions? Additionally, the bolded appears to be a redundant statement. Additionally, it is unclear exactly where the toxin is being administered, as the metes and bounds of “proximal” are not clearly stated.
Claims 4 and 5 are vague and indefinite due to parentheticals because it is unclear if the bladder pain syndrome is to be specifically, interstitial cystitis, or if this merely an example. The use of the parentheticals is confusing. Appropriate clarification and/or correction is required.
Claim 17 is vague and confusing because it is unclear what ‘chimeric neurotoxin’ is being claimed. Is this chimeric with something other than clostridial toxin? Are these different clostridial toxins? The metes and bounds of this term cannot readily be understood. While the specification can be used to provide definitive support, the claims are not read in a vacuum. Rather, the claim must be definite and complete in and of itself. Limitations from the specification will not be read into the claims. The claims as they stand are incomplete and fail to provide adequate structural properties to allow for one to identify what is being claimed. Appropriate clarification and/or correction is required.
Claim Rejections - 35 USC § 112-Enablement
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 2 and 4-17 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Instant claim 2 recites:
A method of suppressing visceral pain in a patient, the method comprising: a. identifying an organ in the patient that is causing the visceral pain;
b. mapping the organ to a specific dermatome nerve according to the following instructions, thereby matching said organ to one or more specifically designated dermatome nerve(s):
i. urinary bladder maps to the T11, T12, L1, S1, S2, S3 and/or S4 dermatome nerve(s);
ii. fallopian tube(s) maps to the T11 dermatome nerve(s);
iii. uterus maps to the T12 and/or L1 dermatome nerve(s);
iv. cervix maps to the S2, S3 and/or S4 dermatome nerve(s);
V. stomach maps to the T8, T9 and/or T10 dermatome nerve(s);
vi. liver maps to the T8, T9, T10 and/or T11 dermatome nerve(s);
vii. gall bladder maps to the T8, T9, T10 and/or T11 dermatome nerve(s);
viii. pancreas maps to the T7, T8, T9, T10, T11 and/or T12 dermatome nerve(s);
ix. small intestine maps to the T10, T11 and/or T12 dermatome nerve(s);
X. colon maps to the T11, S1, S2, S3 and/or S4 dermatome nerve(s);
xi. kidney maps to the T10, T11, T12 and/or L1 dermatome nerve(s);
xii. ureter maps to the T11, T12 and/or L1 dermatome nerve(s);
xiii. ovary maps to the T11 dermatome nerve(s);
xiv. testes maps to the T10, T11, L1, L2, S1, S2, S3 and/or S4 dermatome nerve(s);
xv. epididymis maps to the T10, T11, L1, L2, S1, S2, S3 and/or S4 dermatome nerve(s); thereby matching the organ to the one or more specifically designated dermatome nerve(s); and
c. administering a therapeutically effective amount of [any] clostridial neurotoxin at a site proximal to the one or more specifically designated dermatome nerve(s), wherein following administration of the clostridial neurotoxin to the patient, the clostridial neurotoxin is transported via retrograde axonal transport to the spinal cord where it binds sensory afferent nerve cells, enters said cells by receptor- mediated endocytosis and suppresses neurotransmitter release therefrom, thereby suppressing said visceral pain, wherein the clostridial neurotoxin is administered by intradermal administration.
The instant specification does not enable this method. The instant specification provides the following examples:
EXAMPLE 1 - Suppression of visceral pain following administration of clostridial neurotoxin [Botulinum Toxin A] to a dermatome "In order to demonstrate that dermatome administration of clostridial neurotoxin can suppress visceral pain, the inventors chose to study pain caused by interstitial cystitis/bladder pain syndrome (IC/BPS) as an exemplary condition. The data demonstrates that appropriate dermatome administration (e.g. to a T12, L1, S2, S3 or S4 dermatome in the case of targeting pain in the bladder) can provide for visceral pain suppression.
This study showed that single injection of clostridial neurotoxin (e.g. BoNT/A aka Dysport) to a dermatome nerve, particularly via intradermal injection, provided anti-nociceptive properties on CYP-induced visceral pain. Allodynia and hyperalgesia induced by CYP were lowered by clostridial neurotoxin/ Dysport (intradermal) injection, with allodynia being a particular target for suppression. Dysport effect was long lasting as clostridial neurotoxin/ Dysport was still efficient 20 days after its administration." The further examples presented in the specification do not seem to be accompanied by any detailed experimental results, such as for Example 1.
The following examples are merely prophetic: EXAMPLE 2 - Suppression of pain caused by bladder pain syndrome EXAMPLE 3 - Suppression of pain caused by endometriosis EXAMPLE 4 - Suppression of pain caused by pancreatitis EXAMPLE 5 - Suppression of pain caused by gastric ulcers. ." Genentech, 108 F.3d at 1366. See also Calgene, 188 F.3d at 1374 ("the teachings set forth in the specification provide no more than a 'plan' or 'invitation' for those of skill in the art to experiment practicing [the claimed invention]; they do not provide sufficient guidance or specificity as to how to execute that plan"); National Recovery Technologies, 166 F.3d at 1198 (stating that patent-in-suit "recognizes a specific need.., and suggests a theoretical answer to that need. It provides a starting point from which one of skill in the art can perform further research in order to practice the claimed invention, but this is not adequate to constitute enablement").
Additionally, the only evidence present in the application concerning therapeutic efficacy is with the use of Botulinum toxin A (Dysport). There is no evidence that tetanus toxin, e.g., another Clostridial toxin, for example, would have any therapeutic activity in the treatment of any pain syndromes. Since tetanus toxin has a different mode of action (mainly acting at the CNS synapse) than botulinum toxin (acting peripherally) it appears that the scope of the present claims goes beyond that justified by the disclosure. Thus, the objective technical problem to be solved can only be formulated as the proposal of alternative therapies for pain. Merely proposing therapies with no clear evidence of efficacy does not sufficiently enable the claims. Genentech Inc. v. Novo Nordisk A/S (CAFC) 42 USPQ2d 1001 clearly states: “Patent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable. See Brenner v. Manson, 383 U.S. 519, 536, 148 USPQ 689, 696 (1966) (stating, in context of the utility requirement, that "a patent is not a hunting license. It is not a reward for the search, but compensation for its successful conclusion.") Tossing out the mere germ of an idea does not constitute enabling disclosure. While every aspect of a generic claim certainly need not have been carried out by an inventor, or exemplified in the specification, reasonable detail must be provided in order to enable members of the public to understand and carry out the invention.”
As noted herein above, the only evidence presented in the application concerning therapeutic efficacy seems to concern Botulinum toxin A only. There is no evidence that tetanus toxin for example would have any therapeutic activity in the treatment of any pain syndromes. Thus, in so far as the claims broadly encompass further clostridial neurotoxins, particularly tetanus toxin it is considered that the subject matter of the claims are not enabled by the specification. Additionally, specification only supports the treatment of further pain such as sarcoidosis or vasculitis (see page 43 lines 31 to 32).
As shown by Blumenfeld, A. US 20050147626 A1, in Example 11, using Botulinum to treat pain is unpredictable. [0211] The patient can be a woman in her 30's with reflex sympathetic dystrophy affecting the right lower extremity status post an ankle fracture 5 years earlier. The pain can be intractable to medical therapy including botulinum toxin type A injections to the painful dematomes. However following botulinum toxin type A injections to the trigeminal and cervical plexus sensory branches (as set forth by Example 10), her pain can gradually diminish. The method of using Botulinum toxin to treat pain can be unpredictable and it varies according to the organ or area being treated. It is noted the claims also refer to treating the broad category of “other pain” or allodynia which the specification defines as a pain that results from a stimulus that is not normally painful. By way of example, a subject suffering from bad sunburn may experience intense pain even to light touch. In more detail, sun exposure can overly sensitize the skin such that wearing a shirt or taking a shower can be very painful. Thus, a sufferer of tactile allodynia (aka static tactile allodynia or mechanical allodynia) may experience pain to touch, such as with resting one's head on a pillow, or with wearing a hat, earrings, or necklace. Similarly, a sufferer of dynamic allodynia may experience pain from lightly brushing one's hair, or from shaving one's face. Allodynia is a condition that is distinct from hyperalgesia, which is a pain stimulus that is more painful than usual. Indeed, as mentioned above, allodynia is by its very definition "pain due to a stimulus that does not usually provoke pain", as opposed to hyperalgesia (increased pain from a stimulus that does usually provoke pain). Allodynia may also be referred to as "hypersensitivity" herein. See page 53, lines 25-36, of the instant specification. The specification provides no working examples of this and it is highly unpredictable and includes a huge number of different types of pain at many different sites that highly vary.
The instant specification does not describe the claimed invention in terms that will "enable any person skilled in the art.., to make and use" the invention commensurate in scope with the claims. At most, the specification will enable a person of ordinary skill in the art to attempt to discover how to practice the claimed invention.
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.
Claim(s) 2 and 4-17 is/are rejected under 35 U.S.C. 103 as being unpatentable over any one of Roshni Ramachandran et al (BRITISH JOURNAL OF PHARMACOLOGY, WILEY-BLACKWELL, UK, vol. 171, no. 18, 28 August 2014 (2014-08-28), pages 4177-4192; provided by Applicants), Borodic et al (WO 2004/078201 A1, Sept. 2004; provided by Applicants), Xiao Lizu et al (Neuropathic pain section; Subcutaneous Injection of Botulinum Toxin A Is Beneficial in Postherpetic Neuralgia", January 2010; provided by Applicants), Williams et al (WO 2021/231672 A1, November 18, 2021; provided by Applicants), Voet et al (US 2003/054975 A1; March 2003; provided by Applicants) and Dadas, C. (US 20060083758 A),
in view of Anonymous: "INTERNATIONAL STANDARDS FOR NEUROLOGICAL CLASSIFICATION OF SPINAL CORD INJURY (ISNCSCI)", Internet: https://asia-spinalinjury.org/July 2, 2021 (2021-07-02), Retrieved from the Internet: URL:https://web.archive.org/web/20210702173206/htps:/asia- spinalinjury.org/wp-content/uploads/2019/10/ASIA-ISCOS- Worksheet_10.2019_PRINT-Page-1-2.pdf; provided by Applicants and Lee et al (Clinical Anatomy. 2008. 21: 363-373; provided by Applicants).
Ramachandran, Borodic, Lizu, Williams, Voet and Dadas teach the treatment of pain by administration of botulinum neurotoxin to a selected dermatome region (see description of each reference below).
Roshini discloses the treatment of migraine by injection of botulinum toxin into the cranial dermatome nerves. It is disclosed that the neurotoxin may be transported retrogradely along the treated nerves. See abstract.
Borodic et al discloses treating headache and facial pain associated with acute recurrent or chronic sinusitis by administering botulinum toxin to a dermatome nerve corresponding to the sinus sensory nerve innervation.
Xiao Lizu et al discloses treatment of postherpetic neuralgia (PHN) by injecting botulinum toxin subcutaneously into the affected dermatome nerves. The administered botulinum toxin is disclosed to undergo retrograde axonal transport and is transcytosed to afferent neurons.
William et al discloses the treatment of cirrhosis including hepatitis involving pain (see page 5 lines 4 to 21) using a botulinum toxin applies to a dermatome nerve.
Voet et al teaches discloses treatment of different types of muscle pain by injecting botulinum toxin type within a dermatome. Examples (1,3,4,6-9) are provided of treatment of patients with different forms of pain by targeting particular dermatome nerves including, for example the dermatome S1 region.
Dadas et al teach methods for preventing or treating a premenstrual disorder by peripheral administration of a botulinum toxin. The botulinum toxin can be administered to or to the vicinity of a trigeminal sensory nerve, thereby preventing or treating one or more of the symptoms of a premenstrual disorder. Paragraph [0064] teaches that primary neurons in the trigeminal ganglion synapse on the main sensory trigeminal nucleus and on the spinal trigeminal nucleus in the brainstem. The spinal nucleus of the trigeminal system extends to the upper cervical spine, where connections with cervical dermatomes exist. These dermatomes are innervated by the cervical plexus, which has sensory branches from C1 to C4. The trigeminal nerve also innervates stretch receptors in the muscles of mastication. The cell bodies of these neurons are in the mesencephalic trigeminal nucleus in the midbrain and pons). At paragraph [0092], Dadas recites that Botulinum toxin has been used to treat post-operative pain and visceral pain (U.S. Pat. No. 6,464,986) and a large number of different pain disorder and conditions. Claim 7 of Dadas recites a method for treating a premenstrual disorder, the method comprising the step of administering a botulinum toxin subdermally, non-intramuscularly in therapeutically effective amount to a trigeminal sensory nerve or to the vicinity of a trigeminal sensory nerve (i.e, this is “in the vicinity or proximal to a dermatome nerve) of the patient with a premenstrual disorder, thereby treating the premenstrual disorder by reducing the occurrence of a symptom of the premenstrual disorder.
Although they do not particularly exemplify treating visceral pain associated with the particular organs of Claim 2, e.g. urinary bladder etc. by selectively administering the neurotoxin to the particular dermatome regions defined in Claim 2, e.g. T11, the common dermatome map used to clinically demonstrate the sites of pathology of a patient with a suspected spinal-nerve lesion was known in the prior art as cited by the Anonymous reference. The common dermatome map to be used clinically is the known American Spinal Injury Associations’ (ASIA) worksheet was well known in the prior art and is cited in the application (see present page 24 line 12 to 29) as evidence of mapping of dermatome regions, as well as in the reference cited above. Lee et al also teaches the clinical importance of dermatomes and provides an evidence based-systematic review of the location and distribution of human dermatomes. They provide a evidence-based map of human dermatomes.
Since it is already known to treat pain syndromes by targeting dermatomes as shown in the teachings of Ramachandran, Borodic, Lizu, Williams, Voet and Dadas, it would have prima facie obvious to one of ordinary skill in the art at the time the invention was made to target alternative pain syndromes, including visceral pain, by administering a clostridial neurotoxin to the appropriate dermatome region mapping to the pain. The prior art discloses the mode of action defined in the claims wherein the administered neurotoxin undergoes retrograde axonal transport. The finding that targeting neurotoxin to dermatome nerves ameliorated pain in an animal model of bladder inflammation as presented in the application does not appear surprising and one of skill in the art would have expected that targeting such a nerve region with Botulinum toxin A would be likely to lead to treatment of pain associated with the nerve region. As shown in the prior art, it is well known that botulinum toxin can be therapeutically used to treat pain arising from such nerve regions.
In so far as the claims define therapies involving Botulinum toxin A (for which evidence of efficacy is provided in Example 1) it is noted that dermatome nerve regions mapping to pain in various organs seem to be known and even common general knowledge by being included in textbooks (see specification page 24 line 12 to 29). The teachings of ‘Anonymous’ above are also cited in the instant specification. Present Figure 1B of the instant specification is disclosed to reproduce a known textbook figure. It is also noted that the application does not seem to report the results of any investigations of any dermatome mapping and seems to rely on prior art disclosure to provide sufficiency of disclosure for this aspect.
Regarding the difference between the claims and the prior art in treating visceral pain associated with the particular organs of Claim 2 by selectively administering the neurotoxin to the particular dermatome regions defined in the claims. It is noted that dermatome nerve regions mapping to pain in various organs seem to be known and even common general knowledge by being included in textbooks (see specification page 24 line 12 to 29). Accordingly, it would have been obvious to one of ordinary skill in the art to target any one of these regions with the intention of relieving pain.
Since it is already known to treat pain syndromes by targeting dermatomes with Botulinum toxin A, it would appear obvious to target alternative pain syndromes including visceral pain by administering a clostridial neurotoxin to the appropriate dermatome region mapping to the pain. The prior art discloses the mode of action defined in the claims wherein the administered neurotoxin undergoes retrograde axonal transport, See particularly the teachings of Roshni Ramachndran et al and Xiao Liu et al. and Dadas with respect to premenstrual pain. The finding that targeting neurotoxin to dermatome nerves ameliorated pain in an animal model of bladder inflammation would have been obvious to one of ordinary skill in the art at the time the invention was made as it would be expected that targeting such a nerve region with Botulinum toxin A would be likely to lead to treatment of pain associated with the nerve region. As shown in the cited prior art references, it is well known that botulinum toxin can be therapeutically used to treat pain arising from such nerve regions and was known in the prior art as treatment for a myriad of different conditions, such as recited in instant claim 4 and claims 5-8. With respect to claims 11, 12 and 14 the cited prior art teaches the use of subsequent/later doses of the clostridial neurotoxin and at more than one injection site per treatment. Additionally, it has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). The frequency and administration of Clostridial toxin often varies according to the individual patient being treated and the type and location of the pain being addressed, and different solutions and parameters appear to work equally as well, and pain is subjective, and dosage and timing can vary. Absent unexpected results, it would have been obvious for one of ordinary skill in the art to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the botulinum art.
Prior art not presently relied upon:
Blumenfeld, A. US 20050147626 A1
Example 11
Use of a Botulinum Toxin to Treat a Pain
[0211] The patient can be a woman in her 30's with reflex sympathetic dystrophy affecting the right lower extremity status post an ankle fracture 5 years earlier. The pain can be intractable to medical therapy including botulinum toxin type A injections to the painful dematomes. However following botulinum toxin type A injections to the trigeminal and cervical plexus sensory branches (as set forth by Example 10), her pain can gradually diminish, and by the fourth, three monthly cycle, she can be weaned off all medical treatments and can function normally.
{0160] Thus, a method according to my invention uses a botulinum toxin to produce a modulating effect on the central nervous system when administered (i.e. injected) into a trigeminal nerve branch and/or ansa cervicalis branch particularly in the C2 and C3 dermatomes. The trigeminal sensory nerve endings that are targeted include the supra-orbital, supra-trochlear, temporo-auricular, greater and lesser occipital nerves. This method leads to decreased sensory afferents to the spinal tract of the nucleus caudalis and thereby to decreased central afferent input to the thalamus and thence to the cortex.
[0055] Thus, primary neurons in the trigeminal ganglion synapse on the main sensory trigeminal nucleus and on the spinal trigeminal nucleus in the brainstem. The spinal nucleus of the trigeminal system extends to the upper cervical spine, where connections with cervical dermatomes exist. These dermatomes are innervated by the cervical plexus, which has sensory branches from C1 to C4. The trigeminal nerve also innervates stretch receptors in the muscles of mastication. The cell bodies of these neurons are in the mesencephalic trigeminal nucleus in the midbrain and pons).
0207] A 40 year old woman can develops reflex sympathetic dystrophy of the right lower extremity following a fall with a fractured fibular that requires surgically stabilization. A trial subcutaneous injection of a botulinum toxin type A along the painful dermatomes can provide no pain relief. The patient can complain of increased leg muscle fatigue after this treatment. She can have chronic renal failure and can be resistant to using oral treatments. A trigeminal targeting approach can be utilized using the protocol established in the above cases. Once again 105 units can be injected. After 2 treatment cycles her pain can decrease to the point that she can once again start an exercise program.
Brin, M. US 20210130445 A1 5/6/21
[0010] In some embodiments, the pain is selected from post-surgical pain, post-operative pain, dental pain, pain associated with burn, wound or kidney stone, pain associated with trauma, traumatic head injury, pain associated with musculo-skeletal disorders, rheumatoid arthritis, osteoarthritis, visceral pain, colitis, pancreatitis, gastritis, ankylosing spondylitis, sero-negative (non-rheumatoid) arthropathies, non-articular rheumatism and peri-articular disorders, and pain associated with cancer, pain associated with sickle-cell anemia, peripheral neuropathy, post-herpetic neuralgia, trigeminal neuralgia, general neuralgia, intercostal neuralgia, glossopharyngeal neuralgia, postherpetic neuralgia.
[0013] In some embodiments, the said pain is acute pain, chronic pain, neuropathic pain, inflammatory pain, visceral pain, nociceptive pain, pain associated with multiple sclerosis, pain associated with irritable bowel syndrome or inflammatory bowel disease, pain associated with dysmenorrhea, pelvic pain, pain associated with cystitis, pain associated with pancreatitis, pain associated with Crohn's disease, pain associated with epilepsy or an epileptic condition, visceral pain, radicular pain, sciatica, back pain, neck pain, severe or intractable pain, breakthrough pain, postsurgical pain, stroke, cancer pain, seizure disorder, causalgia and/or chemo-induced pain. In some embodiments, the pain is pain is acute pain. In some embodiments, the pain is chronic pain.
[0014] In some embodiments, the clostridial derivative is a botulinum toxin. In one embodiment, the clostridial derivative is on a botulinum toxin A. In some embodiments, the methods relate to administering to the patient a CGRP-antagonist, and a botulinum toxin, preferably on a botulinum toxin A. In embodiments, the combination therapy of botulinum toxin and a CGRP antagonist reduces the frequency, severity and/or duration of pain in patients in need thereof.
20. The method according to claim 2 wherein said botulinum toxin is administered once every four weeks, five weeks, six weeks, seven weeks, eight weeks, nine weeks or ten weeks.
21. The method according to claim 2 wherein said clostridial derivative is administered to a peripheral nerve, a cranial nerve, or combinations thereof.
22. The method according to claim 9 wherein said anti-calcitonin gene-related peptide receptor antibody is administered to a peripheral nerve, a cranial nerve, or combinations thereof.
Correspondence regarding this application should be directed to Group Art Unit 1645. Papers related to this application may be submitted to Group 1600 by facsimile transmission. Papers should be faxed to Group 1600 via the PTO Fax Center located in Remsen. The faxing of such papers must conform with the notice published in the Official Gazette, 1096 OG 30 (November 15,1989). The Group 1645 Fax number is 571-273-8300 which is able to receive transmissions 24 hours/day, 7 days/week.
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Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jennifer E. Graser whose telephone number is (571) 272-0858. The examiner can normally be reached on Monday-Friday from 8:00 AM-4 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Thomas Visone, can be reached at (571) 270-0684.
Any inquiry of a general nature or relating to the status of this application should be directed to the Group receptionist whose telephone number is (571) 272-0500.
/JENNIFER E GRASER/ Primary Examiner, Art Unit 1645 8/3/26
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