DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application is being examined under the pre-AIA first to invent provisions.
Status of Application, Amendments and/or Claims
2. The amendment of 23 May 2025 has been acknowledged and entered in full. Claims 1, 3-4, 6-9 and 11-12 have been amended. Claims 13-24 and 26-30 are canceled. Claims 1-12 and 25 are currently pending.
3. Amended claim 3 is directed to “additional disorder”(s), a species of which was required to be elected in the office action dated 3/19/2024 (para 6). Applicant responded by election of Delayed sleep phase disorder (DSPS) without traverse on 5/16/2024, which has now been canceled in claim 3. Currently amended claim 3 only recites the non-elected species. Each of the additional disorders of claim 3 will determine characteristically different etiology, and pathology, requiring different treatment strategies, from one another and, therefore, represents a patentably distinct invention and would require a separate search of the art that would be burdensome to the examiner. Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claim 3 is withdrawn from consideration as being directed to a non-elected invention. See 37CFR 1.142(b) and MPEP § 821.03.
4. Claim 3 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 16 May 2024.
5. Claims 1-2, 4-12 and 25 drawn to a method of treating spastic disorder and sleep disorder in a subject comprising administering botulinum toxin, are being considered for examination in the instant application.
Withdrawn Rejections
6. Upon consideration of amendment of claims, the rejections under 35 U.S.C. 102(b) and 35 U.S.C. 103(a) have been withdrawn.
7. Upon consideration of amendment of claims, the rejections under nonstatutory double patenting have been withdrawn.
New Rejections – necessitated by current amendment
Claim Rejections - 35 USC § 103
8. The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the
basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
9. Claims 1-2, 4-5, 7-10, are rejected under 35 U.S.C. 103(a) as being unpatentable over Davis et al (J Neurol Neurosurg Psychiat 69: 143-149, 2000) and Gracies JM (Movement Disorders 19: S120-S128, 2004), in view of Jan et al (Dev Med Child Neurol 46: 776-782, 2004), and as evidenced by Sharma et al (Toxicon 41: 321-331, 2003).
10. The claims are directed to a method of simultaneously treating a spastic disorder and a sleep disorder in a subject, comprising identifying a subject with both spastic and sleep disorder and administering an effective amount of a pharmaceutical composition comprising a botulinum toxin and a pharmaceutically acceptable carrier; thereby simultaneously reducing at least one symptom of the spastic as well as of the sleep disorder, wherein: the sleep disorder is delayed sleep phase disorder (DSPD) (claim 1); the administering comprises at least two multifocal injections selected from the recited modes of administration (claims 2, 7-10); and the toxin is a type A botulinum toxin (claim 4) from a Hall strain Clostridium botulinum (claim 5).
11. Davis et al teach the use of botulinum toxin A in humans (Dysport® and BOTOX®, which are commercially purified formulations for clinical use, i.e., pharmaceutical compositions) for treating spasticity (spastic disorder) (page 143, para spanning cols 1, 2; page 144, col 1, para 4). The reference teaches that spasticity leads to significant pain and contractures, and the treatment alleviates pain (page 144, para spanning cols 1, 2). Davis et al particularly teach that spasticity is present in cerebral palsy, wherein the spastic muscle tone is reduced by botulinum, thereby treating the upper and lower limb spasticity in this condition. The reference also teaches injections of botulinum toxin A in different muscles (e.g., paraspinous and lower limb muscles) (intramuscular and multifocal), thereby improving positioning and gait (page 145, col 1, para 3, 4 – Cerebral palsy) (instant claims 2, 4, 7-10). Davis et al do not teach that the toxin is from the Hall strain of Clostridium botulinum. However, this would be evident from Sharma et al teaching that botulinum neurotoxin type A (BoNT/A) is found in bacterial cultures of Clostridium botulinum type A (Abstract), is grown and purified using the Hall strain of the bacteria (page 322, Methods, Sections 2.1., 2.2.), and that the BoNT/A composition complex is used in 2 medicinal formulations (pharmaceutical composition) – Dysport and Botox (page 329, sentence spanning cols 1, 2) (instant claim 5). Even though Davis et al do not explicitly mention “a pharmaceutically acceptable carrier” (claim 1), this would be a necessary feature of the known pharmaceutical compositions taught in the reference. That is, pharmaceutically acceptable carriers would understandably be present along with the active drug, as per basic requirements of any medicinal formulation.
12. Gracies teaches that botulinum toxin (BTX) lowers spastic contraction of injected muscle, and reduces spastic dystonia (page S125, concluding para). The reference teaches that intramuscular BTX injections have central effects including the reduction of motoneuronal excitability (Abstract; page S121, col 1, last para and col 2, para 3).
13. Davis et al or Gracies do not teach that the subject with spastic disorder has delayed sleep phase disorder.
14. Jan et al teach that children with multiple disabilities including cerebral palsy have a high prevalence of circadian rhythm sleep disorders (CRSD) with sleep difficulties (page 776, col 1, para 1; col 2, para 1), wherein the most common CRSD in such children is delayed sleep phase onset (delayed sleep phase disorder or DSPD) (page 777, col 2, para 2, 3), suggesting that spasticity and DSPD are comorbid conditions. Jan et al also teach CRSDs like delayed sleep phase onset (or DSPD) in individuals with such disabilities can be easily treated with medications like melatonin, which "is known to inhibit neuronal excitability" in the CNS (page 777, col 2, para 2). Jan et al further teach that melatonin can not only treat sleep disturbance, but also reduce spasticity in children with cerebral palsy (page 777, col 2, para 3), i.e. the method of Jan necessarily implies “identifying a subject with both said spastic disorder and said sleep disorder”. The reference therefore, indicates that therapeutics used for treating a spastic disorder can also treat a sleep disorder in the same subject, thereby simultaneously treating a spastic disorder and a sleep disorder in a subject (instant claim 1).
15. The preamble of claim 1 recites a method for “simultaneously treating a spastic disorder and a sleep disorder in a subject”; however, this is the purpose of the claimed therapeutic method and thus has been given its proper weight. MPEP 2111.02(II) states that “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention's limitations, then the preamble is not considered a limitation and is of no significance to claim construction”. Here, the body of the claim sets forth all the steps and starting materials, and the preamble of the claim merely recites a purpose for the steps. Additionally, with respect to the limitation of claim 1 (lines 7, 8) reciting “thereby simultaneously reducing at least one symptom…. subject” indicates a result of the method, but not a step that is to be performed by the artisan. Upon performing the steps: (i) identifying a subject…..; and (ii) administering an effective amount…. ; one will necessarily have simultaneously reduced at least one symptom, of both - the spastic disorder and of the sleep disorder. It is noted that the only 2 steps are those listed as (i) and (ii) in the claim, and that there are no further steps for determining reduction of the symptoms, for example.
16. It would therefore, have been obvious to one skilled in the art at the time the invention was made to modify the administration of botulinum toxin for treating spastic disorder in a subject as taught by Davis et al and Gracies, by also treating sleep disorder in the same subject based upon the teachings of Jan et al. The person of ordinary skill in the art would have been motivated to identify and treat a spastic disorder and sleep disorder in the same subject because it was recognized that sleep disorders coexist in spasticity conditions (e.g. cerebral palsy). The person of ordinary skill in the art would also have been motivated to perform the simultaneous treatment of both conditions (spasticity and sleep disorder) with botulinum, as a single therapeutic agent, because reducing neuronal excitability was demonstrated to be effective for both reducing spasticity and sleep disturbances in the same subject (Jan et al). Given the demonstrated effectiveness of another agent (melatonin) to simultaneously treat a spastic disorder and reduce sleep disturbances, the artisan would have had a reasonable expectation that the known spasticity-reducing agent botulinum toxin could also be successfully employed to simultaneously reduce sleep disturbances in a subject. The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of the prior art references.
17. Thus, the claimed invention as a whole was prima facie obvious over the teachings of the prior art.
18. Claims 1-2, 4-12 and 25 are rejected under 35 U.S.C. 103(a) as being unpatentable over Davis et al (2000), Gracies (2004) and Jan et al (2004) in view of Borodic et al (Ophthal Plastic Reconstructive Surg 9: 182-190, 1993), in further view of Blumenfeld (USP 8734810, filed 10/12/2004), as evidenced by Sharma et al (2003).
19. The claims also recite that the pharmaceutical composition comprises botulinum toxin in an amount from 1.25 to 3000 units (U) or 100 units (claims 11-12); and the pharmaceutically acceptable carrier is one selected from the list recited in claim 25. Claim 6 recites that the botulinum toxin is type B toxin.
20. The teachings of Davis et al, Gracies and Jan et al are set forth above. Davis et al also teach the use of botulinum toxin type B which is clinically “effective, safe and well tolerated” in both A responders and non-responders (page 143, col 2, para 3), indicating that the type B toxin can also be used for treating spasticity.
21. Borodic et al teach that botulinum types A and B neurotoxins exhibit many “functional, structural and mechanistic similarities” (page 185, Discussion, para 1). The reference suggests that both toxins exert similar pharmacological effects on muscle innervation (Summary).
22. Davis et al, Gracies, Jan et al or Borodic et al do not teach the carriers and the units as instantly recited in claims 1, 11-12 and 25.
23. Blumenfeld generally teaches that the botulinum toxins (A, B) of the invention are present in pharmaceutical compositions comprising pharmaceutically acceptable carriers such as an excipient, saline or water (salt) (col 25, lines 54-59) (instant claim 25), which can be used at multiple injection sites (or multifocal) (col 21, lines 43-44), in amounts of about 1 to about 3000 units or about 100 units (col 20, lines 1-5). The reference teaches the use of MYOBLOC® (botulinum toxin B) at 40-2500 U (col 34, lines 1-4, 15-16; col 21, lines 31-36) (instant claims 11-12, 25). Even though the reference does not teach treating spastic disorder using Botulinum B, the reference clearly contemplates the use of either botulinum A or B toxins for treatment.
24. The pharmaceutically acceptable carriers and the units of botulinum toxins A and B are therefore, rendered as obvious over the combined teachings of Davis et al, Jan et al, Borodic et al and Blumenfeld.
25. Davis et al, Gracies, Jan et al, Borodic et al or Blumenfeld do not explicitly teach the use of botulinum toxin B for treating spastic disorder (as recited in instant claim 6).
26. It would however, be obvious to one skilled in the art at the time the invention was made to substitute botulinum toxin type A, with botulinum toxin type B for treating spastic disorder in view of the combined teachings of Davis et al, Gracies, Jan et al, Borodic et al and Blumenfeld. Because of functional/mechanistic similarity and therapeutic effectiveness between botulinum toxin types A and B, it would be obvious to one of ordinary skill in the art to have a simple substitution of functionally equivalent elements, i.e., the substitution of botulinum toxin type A for botulinum toxin type B with predictable results (MPEP 2143 (B)). The person of ordinary skill in the art would have been motivated to try modifying the method of treating spastic disorder using botulinum toxin type B, as this subtype is recognized as being an “effective, safe and well tolerated” therapeutic in both type A responders and non-responders (Davis et al). The person of ordinary skill in the art would also have been motivated as botulinum toxin type B (like botulinum toxin type A) is not only commercially available, it is also FDA approved for treating diseases involving hyperactive muscles like cervical dystonia (a spastic disorder) (Blumenfeld, col 11, lines 49-53). The person of ordinary skill in the art would have had a reasonable expectation of success based on the cumulative disclosures of the prior art references.
27. Thus, the claimed invention as a whole was prima facie obvious over the teachings of the prior art.
Applicant’s Remarks:
28. Applicant argues that none of the references anticipate amended claim 1 or its dependent claims. Applicant also argues that the cited references used alone or in combination fail to teach or suggest each and every element of amended independent claim 1. Reiterating the teachings and highlighting the deficiencies of each of the cited art, Applicant argues that at the time of the invention, a person of ordinary skill would not have combined the teachings of the cited art to arrive at the method as instantly claimed with a reasonable expectation of success. Applicant emphasizes that one of ordinary skill in the art would have no reason or motivation to “identify a subject with both spastic disorder….”, or assume that botulinum toxin type A would reduce at least one symptom of the claimed disorders, without using impermissible hindsight. Applicant therefore, requests withdrawal of the 102 and 103 rejections.
29. Applicant’s arguments about anticipation are fully considered and found to be persuasive. The rejection is now withdrawn.
30. Applicant’s arguments traversing the 103 rejections are fully considered. The teachings and deficiencies had been stated and acknowledged in the previous Office Action. Upon consideration of amendment of independent claim 1, new rejections have been set forth. As stated above, treating spastic disorder with botulinum toxin (Davis, Gracies), wherein spasticity is known to coexist with circadian rhythm sleep disorders (Jan), and both said disorders can be simultaneously treated in the same subject (or a symptom can be reduced) by administration of a therapeutic (Jan et al), was known to the person of ordinary skill at the time of the present invention. Therefore, the teaching, suggestion and motivation to combine the references provided an appropriate rationale for determining obviousness. The person of ordinary skill in the art would have been motivated to treat both conditions with botulinum, as a single therapeutic was proven to be effective for reducing spasticity as well as sleep disturbances in the same subject, with a reasonable expectation of success based on the cumulative disclosures of the prior art references.
31. Applicant’s argument over the shortcomings of each of the references is considered. Applicant is however, reminded that the rejections are based on the combined teachings of the art to determine obviousness. One cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
32. Applicants may argue that the examiner's conclusion of obviousness is based on improper hindsight reasoning. However, "[a]ny judgement on obviousness is in a sense necessarily a reconstruction based on hindsight reasoning, but so long as it takes into account only knowledge which was within the level of ordinary skill in the art at the time the claimed invention was made and does not include knowledge gleaned only from applicant's disclosure, such a reconstruction is proper." In re McLaughlin 443 F.2d 1392, 1395, 170 USPQ 209, 212 (CCPA 1971).
Double Patenting
33. Non-Statutory
34. The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); and In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
35. A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on a nonstatutory double patenting ground provided the conflicting application or patent either is shown to be commonly owned with this application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement.
36. Effective January 1, 1994, a registered attorney or agent of record may sign a terminal disclaimer. A terminal disclaimer signed by the assignee must fully comply with 37 CFR 3.73(b).
37. Claims 1-2, 4-12 and 25 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 4, 41, 49, 50, 51 of US Patent 7,691,394 in view of Davis et al (2000)/Gracies (2004), Jan et al (2004), Borodic et al (1993) and Blumenfeld (2004). Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to treating subjects having a muscle spasticity or cervical dystonia (spastic disorder) or pain, comprising administering botulinum toxin type A in amounts that fall within the instantly recited range of 1.25 to 3000 units to said subjects.
The only differences between the 2 sets of claims are:
i) Instant claims recite that the subject having spastic disorder also has sleep disorder, while ‘394 claims do not recite sleep disorder. However, this would necessarily be prevalent in subjects with muscle spasticity, and a symptom of both spastic disorder and sleep disorder can be identified and treated in the same subject in view of Davis et al, Gracies and Jan et al, as stated above.
ii) Instant claims also recite administration of botulinum toxin type B, while the ‘394 claims do not have this limitation. However, it would be obvious to substitute botulinum toxin type A, with botulinum toxin type B for treating spastic disorder in view of Davis et al, Borodic et al and Blumenfeld, for reasons stated above.
38. Therefore, the instant claims are not patentably distinct over the issued claims in U.S. patent 7,691,394.
39. Claims 1-2, 4-12 and 25 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 5-7, 11, 13-14, 18-19, 22 of US Patent 6,429,189 in view of Davis et al (2000)/Gracies (2004), Jan et al (2004), Borodic et al (1993) and Blumenfeld (2004). Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to treating subjects having pain caused by spasmodic torticollis (cervical dystonia – spastic disorder), comprising administering botulinum toxin.
The only differences between the 2 sets of claims are:
i) Instant claims recite that the subject having spastic disorder also has sleep disorder, while ‘189 claims do not recite sleep disorder. However, this would necessarily be prevalent in subjects with muscle spasticity, and a symptom of both spastic disorder and sleep disorder can be identified and treated in the same subject in view of Davis et al, Gracies and Jan et al, as stated above.
ii) Instant claims recite administration of botulinum toxin types A or B, while the ‘189 claims do not have such limitation. However, it would be obvious to use botulinum toxin types A or B, for treating spastic disorder in view of Davis et al, Borodic et al and Blumenfeld, for reasons stated above.
40. Therefore, the instant claims are not patentably distinct over the issued claims in U.S. patent 6,429,189.
41. Claims 1-2, 4-12 and 25 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-9 of US Patent 10,441,641 in view of Davis et al (2000)/Gracies (2004), Au et al (Ann Acad Med Singapore 33: 324-8, 2004), Jan et al (2004), Borodic et al (1993) and Blumenfeld (2004). Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to treating subjects having a sleep disorder, sleep onset or sleep maintenance insomnia comprising administering a pharmaceutical composition comprising botulinum toxin type A by injection, using subcutaneous or intramuscular modes in amounts between 5 to 3000 units of said subjects.
The only differences between the 2 sets of claims are:
i) Instant claims recite treating spastic disorder and a DSPD in a subject, while claims of the ‘641 patent recite treating sleep disorder (sleep onset insomnia or DSPD) and depression. However, this would be obvious in view of the teachings of Au et al. Au et al teach that 65% of hemifacial spasm (spastic disorder because it involves involuntary contractions of facial muscles) patients have depression, adding that an effective treatment using botulinum toxin can be provided (Abstract). Moreover, the presence of sleep disorder is prevalent in subjects with muscle spasticity, and a symptom of both spastic disorder and sleep disorder can be identified and treated in the same subject in view of Davis et al, Gracies and Jan et al, as stated above.
ii) Instant claims also recite administration of botulinum toxin type B, while the ‘641 claims do not have this limitation. However, it would be obvious to substitute botulinum toxin type A, with botulinum toxin type B for treating spastic disorder in view of Davis et al, Borodic et al and Blumenfeld, for reasons stated above.
42. Therefore, the instant claims are not patentably distinct over the issued claims in U.S. patent 10,441,641.
43. Claims 1-2, 4-12 and 25 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 3, 5-10,12-13,15,18, 22, 25,29-30 of co-pending application number 17/234,690 in view of Davis et al (2000)/Gracies (2004), Au et al (2004), Jan et al (2004) and Blumenfeld (2004). Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to treating a subject having a symptom of depression such as insomnia (e.g., sleep onset insomnia or DSPD), comprising administering botulinum toxin to said subjects, wherein the administration is multifocal, and the delivery is by non-intramuscular (e.g., transdermal, subcutaneous etc.) routes.
The only differences between the two sets of claims are:
i) Instant claims recite treating a spastic disorder and a sleep disorder in a subject, while claims of the ‘690 application recite treating sleep disorder and depression. However, this would be obvious in view of the teachings of Davis et al, Jan et al and Au et al for reasons stated above. Therefore, spasticity, depression and sleep disorders co-exist in the same subject. Moreover, the presence of sleep disorder is prevalent in subjects with muscle spasticity, and a symptom of both spastic disorder and sleep disorder can be identified and treated in the same subject in view of Davis et al, Gracies and Jan et al, as stated above.
ii) Instant claims recite administration of botulinum toxin types A or B, while the ‘690 application claims are generic. However, treating spastic disorders known to be associated with depression by administering botulinum toxin type A or botulinum toxin type B, would be obvious in view of the teachings of Blumenfeld as stated above.
44. This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
45. Claims 1-2, 4-12 and 25 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-19 of US Patent 8,926,991, in view of in view of Davis et al (2000)/Gracies (2004), Jan et al (2004), Borodic et al (1993) and Blumenfeld (2004).
Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to treating subjects having sleep disorder (sleep onset insomnia or DPSD), comprising administering botulinum toxin type A to said subjects, wherein the administration is multifocal, and the delivery is by transdermal, subcutaneous or intramuscular injections.
The only differences between the 2 sets of claims are:
i) Instant claims recite treating spastic disorder in a subject having a sleep disorder, while claims of the ‘991 patent only recite treating sleep disorder. However, DSPD is prevalent in subjects with muscle spasticity in view of Davis et al, Gracies and Jan et al, as stated above. Since both conditions (spasticity and DSPD) can be treated with botulinum toxin A, and since both conditions coexist in a subject, it would be obvious to treat a subject with spasticity and sleep disorder. That is a symptom of both spastic disorder and sleep disorder can be identified and treated in the same subject in view of the cited references.
ii) Instant claims also recite administration of botulinum toxin type B, while the ‘991 claims do not have this limitation. However, it would be obvious to substitute botulinum toxin type A, with botulinum toxin type B for treating spastic disorder in view of Borodic et al and Blumenfeld, for reasons stated above.
46. Therefore, the instant claims are not patentably distinct over the issued claims in U.S. patent 8,926,991.
47. Claims 1-2, 4-12 and 25 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 10-19, 22, 25-26, 28 and 30 of co-pending application number 18/455179, in view of Davis et al (2000), Borodic et al (1993) and Blumenfeld (2004), and evidenced by Spasticity <What Is Spasticity? Symptoms, Causes, Diagnosis, and Treatment (everydayhealth.com)> (downloaded on 6/24/24, 13 pages). Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to treating subjects with spasticity (cervical dystonia or spasmodic torticollis is associated with involuntary muscle contractions, therefore, is a spastic disorder) and DSPD, comprising administering an effective amount of botulinum toxin type A to said subjects, wherein the administration is multifocal and the delivery is by intramuscular, subcutaneous or transdermal route, in an amount of 1.25 to 3000 units.
The only differences between the two sets of claims are:
i) Instant claims recite treating spastic disorder in a subject having DSPD, while claims of the ‘179 application recite treating cervical dystonia and DSPD. However, this would be obvious as dystonia conditions having involuntary contractions and spasm are related to spasticity, as evidenced by Spasticity (page 1, para 1; page 2, Signs and symptoms associated with spasticity; page 8, Conditions Related to Spasticity). Instant claims are therefore, directed to a genus of spastic disorders.
ii) Instant claims also recite administration of botulinum toxin type B, while the ‘179 claims do not have this limitation. However, it would be obvious to substitute botulinum toxin type A with botulinum toxin type B in view of Davis et al, Borodic et al and Blumenfeld, for reasons stated above.
48. This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
49. Claims 1-2, 4-12 and 25 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 3-4, 9-11, 16, and 18-25 and 30-31 of co-pending application number 18/521,777, in view of Davis et al (2000), Gracies (2004) and Jan et al (2004). Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to treating subjects, comprising administering an effective amount of botulinum toxin type A or type B to said subjects, wherein the injection is multifocal and the delivery is selected from the recited routes, in doses of 1.25 to 3000 units.
The only difference between the two sets of claims is:
The ‘777 claims broadly recite treating circadian rhythm disorder in a subject, while instant claims recite treating a subject with spastic disorder having DSPD, wherein DSPD is a circadian rhythm disorder as stated in para 0065 of instant specification. Additionally, DSPD is prevalent in subjects with muscle spasticity, and a symptom of both spastic disorder and sleep disorder can be identified and treated in the same subject in view of Davis et al, Gracies and Jan et al, as stated above.
50. This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
51. Claims 1-2, 4-12 and 25 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-9, 20, 24-26 of co-pending application number 17/135,938, in view of Davis et al (2000), Gracies (2004), Jan et al (2004), Borodic et al (1993) and Blumenfeld (2004). Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to treating subjects with pain (spastic disorders are associated with pain) and sleep onset insomnia (DSPD), comprising administering an effective amount of botulinum toxin type A to said subjects from 1.25 units to 3000 units, wherein: the administration is multifocal and the delivery is by subcutaneous, transdermal or intramuscular route.
The only differences between the two sets of claims are:
i) Instant claims recite treating a spastic disorder in a subject having DSPD, while claims of the ‘938 application recite treating sleep disorder and pain syndromes. However, this would be obvious in view of the teachings of Davis et al and Jan et al (stated above) showing that spasticity leads to significant pain and contractures. Additionally, DSPD is prevalent in subjects with muscle spasticity, and a symptom of both spastic disorder and sleep disorder can be identified and treated in the same subject in view of Davis et al, Gracies and Jan et al, as stated above.
ii) Instant claims also recite administration of botulinum toxin type B, while the ‘938 claims do not have this limitation. However, it would be obvious to substitute botulinum toxin type A, with botulinum toxin type B in view of Davis et al, Borodic et al and Blumenfeld, for reasons stated above.
52. This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
53. Claims 1-2, 4-12 and 25 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-4, 8-18, 30-33, and 45-46 of US Patent 9,956,435, in view of Davis et al (2000), Gracies (2004), Jan et al (2004) and Blumenfeld (2004).
Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to treating subjects having muscle spasm (i.e., spastic disorders), comprising administering botulinum toxin type A or B to said subjects.
The only differences between the 2 sets of claims are:
i) Instant claims recite treating spastic disorder in a subject having a DSPD, while claims of the ‘435 patent only recite treating muscle spasm. However, it would be obvious in view of Davis et al, Gracies and Jan et al that spastic disorders are associated with muscle spasm, and that DSPD is prevalent in spasticity. DSPD is a prevalent condition in subjects with muscle spasticity, and a symptom of both spastic disorder and sleep disorder can be identified and treated in the same subject in view of the cited art, as stated above.
ii) Instant claims recite modes of administration of botulinum toxin, while the ‘435 claims do not have such limitation. However, this would be obvious in view of Blumenfeld, for reasons stated above.
54. Therefore, the instant claims are not patentably distinct over the issued claims in U.S. patent 9,956,435.
55. Claims 1-2, 4-12 and 25 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 4, and 11-13 of US Patent 8,518,414, in view of Davis et al (2000), Gracies (2004), Jan et al (2004), Borodic et al (1993) and Blumenfeld (2004).
Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to treating subjects having muscle spasm (i.e., spastic disorders, dystonia), comprising transdermally administering botulinum toxin to said subjects.
The only differences between the 2 sets of claims are:
i) Instant claims recite that the subject with spastic disorder also has DSPD, while claims of the ‘414 patent do not recite sleep disorder or DSPD. However, it would be obvious in view of Davis et al and Jan et al teaching that spastic disorders having muscle spasm or contractions show a prevalence of DSPD. DSPD is therefore, a comorbid condition in subjects with muscle spasticity, and a symptom of both spastic disorder and sleep disorder can be identified and treated in the same subject in view of Davis et al, Gracies and Jan et al, for reasons stated above.
ii) Instant claims recite botulinum toxin type A or B, while the ‘414 claims are generic. However, treating spastic disorders by administering botulinum toxin type A or botulinum toxin type B, would be obvious in view of the teachings of Davis et al, Borodic et al and Blumenfeld for reasons stated above.
56. Therefore, the instant claims are not patentably distinct over the issued claims in U.S. patent 8,518,414.
57. Claims 1-2, 4-12 and 25 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 3-6, 48-49, 53-54, 56-57, 60-62, of US Patent 9,211,248, in view of Davis et al (2000), Gracies (2004), and Jan et al (2004).
Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to treating subjects having muscle spasm pain (spastic disorders are associated with muscle spasm and pain), comprising transdermally administering a composition comprising botulinum toxin type A or B and a pharmaceutically acceptable carrier having polymeric backbone (pharmaceutically acceptable polymeric material) to said subjects.
The only difference between the 2 sets of claims is:
Instant claims recite that the subject with muscle spasm (spastic disorder) also has DSPD, while claims of the ‘248 patent do not recite sleep disorder. However, it would be obvious in view of Davis et al and Jan et al that spastic disorders having muscle spasm are associated with pain and a prevalence of DSPD. DSPD is a prevalent condition in subjects with muscle spasticity, and a symptom of both spastic disorder and sleep disorder can be identified and treated in the same subject in view of Davis et al, Gracies and Jan et al, as stated above.
58. Therefore, the instant claims are not patentably distinct over the issued claims in U.S. patent 9,211,248.
59. Claims 1-2, 4-12 and 25 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 6-8, 10, 17 of co-pending application number 17/951,220, in view of Davis et al (2000), Gracies (2004), Jan (2004), Borodic et al (1993) and Blumenfeld (2004). Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to treating subjects having spastic disorders (hemifacial spasm, spasmodic torticollis, cerebral palsy, etc.), comprising injecting a composition comprising botulinum toxin and a pharmaceutically acceptable carrier to said subjects.
The only differences between the two sets of claims are:
i) Instant claims recite that the subject with spastic disorder also has DSPD, while claims of the ‘220 application do not recite sleep disorder. However, it would be obvious in view of Davis et al and Jan et al teaching that spastic disorders show a prevalence of DSPD. DSPD is a comorbid condition in subjects with muscle spasticity, and a symptom of both spastic disorder and sleep disorder can be identified and treated in the same subject in view of Davis et al, Gracies and Jan et al, for reasons stated above.
ii) Instant claims recite modes of administration and doses of botulinum toxin type A or B, while the ‘220 claims are generic. However, treating spastic disorders known to be associated with spasmodic torticollis (cervical dystonia) by administering botulinum toxin type A or botulinum toxin type B, would be obvious in view of the teachings of Davis et al, Borodic et al and Blumenfeld for reasons stated above.
60. This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
61. Claims 1-2, 4-12 and 25 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1, 5-7, 20-22, 24-25, 31-32, 40, 50-52, of co-pending application number 18/595,365, in view of Davis et al (2000), Gracies (2004), Jan (2004), and Blumenfeld (2004). Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to treating subjects having spastic disorders (hemifacial spasm, spasmodic torticollis, cerebral palsy, etc.), comprising injecting a composition comprising botulinum toxin type A and a pharmaceutically acceptable carrier to different muscles (intramuscular and multifocal) of said subjects.
The only differences between the two sets of claims are:
i) Instant claims recite that the subject with spastic disorder also has DSPD, while claims of the ‘365 application do not recite sleep disorder. However, it would be obvious in view of Davis et al and Jan et al that spastic disorders show a prevalence of DSPD. DSPD is a comorbid condition in subjects with muscle spasticity, and a symptom of both spastic disorder and sleep disorder can be identified and treated in the same subject in view of Davis et al, Gracies and Jan et al, as stated above.
ii) Instant claims also recite administration of botulinum toxin type B, while the ‘365 claims are silent in this regard. However, treating spastic disorders by administering botulinum toxin type A or botulinum toxin type B comprising doses as instantly claimed, would be obvious in view of the teachings of Blumenfeld as stated above.
62. This is a provisional obviousness-type double patenting rejection because the conflicting claims have not in fact been patented.
63. Claims 1-2, 4-12 and 25 are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-9, 11-12, 22 of US Patent 10,080,786, in view of Davis et al (2000), Gracies (2004) and Jan et al (2004).
Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to treating subjects having muscle spasm pain (spastic disorders are associated with muscle spasm and pain), comprising transdermally administering a composition comprising botulinum toxin type A or B and a pharmaceutically acceptable carrier having polymeric backbone (pharmaceutically acceptable polymeric material) or a gelling agent to said subjects.
The only difference between the 2 sets of claims is:
Instant claims recite that the subject with muscle spasm (spastic disorder) also has DSPD, while claims of the ‘786 patent do not recite sleep disorder. However, it would be obvious in view of Davis et al and Jan et al that spastic disorders having muscle spasm are associated with pain and show a prevalence of DSPD. DSPD is a coexisting condition in subjects with muscle spasticity, and a symptom of both spastic disorder and sleep disorder can be identified and treated in the same subject in view of Davis et al, Gracies and Jan et al, as stated above.
64. Therefore, the instant claims are not patentably distinct over the issued claims in U.S. patent 10,080,786.
65. Claims 1-2, 4-12 and 25 are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-9 of US patent 12,257,293 issued on 3/25/2025, in view of Davis et al (2000), Gracies (2004), Jan (2004), Borodic (1993) and Blumenfeld (2004). Although the conflicting claims are not identical, they are not patentably distinct from each other because in each case the claims are directed to treating subjects having spastic disorders (cervical dystonia), comprising intramuscularly injecting a composition comprising botulinum toxin type A and a pharmaceutically acceptable carrier to said subjects in doses of 100 to 300 U into different muscles (multifocal).
The only differences between the two sets of claims are:
i) Instant claims recite that the subject with spastic disorder also has DSPD, while claims of the ‘293 patent do not recite sleep disorder. However, it would be obvious in view of Davis et al and Jan et al that spastic disorders show a prevalence of DSPD. DSPD is a coexisting condition in subjects with muscle spasticity, and a symptom of both spastic disorder and sleep disorder can be identified and treated in the same subject in view of Davis et al, Gracies and Jan et al, for reasons stated above.
ii) Instant claims recite botulinum toxin type A or B, while the ‘293 patent claims only recite botulinum toxin subtype A. However, treating spastic disorders like spasmodic torticollis (cervical dystonia) by administering botulinum toxin type A or botulinum toxin type B, would be obvious in view of the teachings of Borodic et al and Blumenfeld for reasons stated above.
66. Therefore, the instant claims are not patentably distinct over the issued claims in U.S. patent 12,257,293.
Note: It is incumbent on the Applicant to inform the office of all related subject matter and to file all related terminal disclaimers. See 37 CFR 1.56, Duty to disclose information material to patentability.
Applicant’s Remarks:
67. Applicant argues each of the rejections, generally alleging that there is no basis to combine the reference patents/applications with the cited literature, as said patents or co-pending applications are silent regarding “treating a subject with a spastic disorder and a sleep disorder”. Applicant asserts that US patent 8,679,486 and 7,537,773 are expired. Applicant states that since claims 13-24 and 26-30 of the present application are cancelled, the rejections of these claims are moot. Applicant requests the rejection over claims of co-pending application 18/455179 be held in abeyance till the identification of allowable subject matter.
68. Applicant’s arguments are fully considered. The amendment of claim 1, and cancellation of instant claims 13-24, 26-30 are noted, and new rejections are set forth with appropriate modifications.
69. Due to the expiration of US patents 8,679,486 and 7,537,773, the double patenting rejections over these patents are withdrawn. Upon consideration of the amendment of claims of co-pending application 17/472525 to only recite treating glabellar lines, the provisional rejection over ‘525 application is withdrawn. The rejection over co-pending application 17/547211 is withdrawn as it is now issued as US patent 12,257,293 (a new rejection is made over the ‘293 patent).
70. The rejections have not been overcome by amendment or the filing of an approved terminal disclaimer. Since no allowable subject matter has yet been identified the rejections are appropriate.
Conclusion
71. No claims are allowed.
72. 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.
74. Any inquiry concerning this communication or earlier communications from the examiner should be directed to Aditi Dutt whose telephone number is (571)272-9037. The examiner can normally be reached on M-F 9:00am-5:00pm.
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/A. D./
Examiner, Art Unit 1675
25 August 2025
/KIMBERLY BALLARD/Primary Examiner, Art Unit 1675