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 .
Status of the Claims
The claim set filed 12/21/2023 is acknowledged. No restriction is being imposed in this case. Claims 1-20 are pending under examination.
Claim Interpretation
The recitation of “lateral to the patient’s spine” in claims 1 and 12 is interpreted as limiting the administration to the area adjacent to the spine. For instance, although there are sacral nerves running to the foot, it is not reasonable to interpret the phrase “lateral to the spine” as encompassing injection of the foot. Further, the recitation of “and/or” in claim 1 encompasses an alternative list and is not limited to administration to each and every nerve type.
In light of the plain meaning of the claim language and the guidance set forth in the instant specification, the injection steps are interpreted as encompassing the number of injections necessary to achieve a therapeutically effective amount or total dosage of 1 to 150 units (see instant claims 3, 5 and 12).
Independent claims 1 and 12 recite preventing a dementia. The instant specification mentions preventive treatment at p. 4, lines 19-23:
The term “treating” includes delaying, alleviating, mitigating or reducing the intensity, progression, or worsening of one or more attendant symptoms of a disorder or condition and/or alleviating, mitigating or impeding one or more causes of a disorder or condition. Treatment under the claimed invention may be a preventative treatment, prophylactic treatment, remission of treating or ameliorating treatment.
In light of this passage and in the context of the claims, “preventing” is interpreted as blocking dementia from occurring.
Effective Filing Date
Applicant’s claim for the domestic benefit of prior-filed applications under 35 U.S.C. 119(e) is acknowledged. Under the AIA , the effective filing date of a claimed invention is the earlier of:
The actual filing date of the application;
OR
The filing date to which the application is entitled to a right of foreign priority or domestic benefit as to such claimed invention.
Note that with regard to claiming domestic benefit of prior-filed applications, MPEP 211.05 sets forth the disclosure requirements:
To be entitled to the benefit of the filing date of an earlier-filed application, the later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or earlier-filed nonprovisional application or provisional application for which benefit is claimed); the disclosure of the invention in the prior application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, except for the best mode requirement. See Transco Prods., Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994). Accordingly, the disclosure of the prior-filed application must provide adequate support and enablement for the claimed subject matter of the later-filed application in compliance with the requirements of 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph, except for the best mode requirement.
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Based on the information given by Applicant and an inspection of the prior application, the examiner has concluded that the subject matter defined in the instant claims is supported by the disclosure in provisional application serial no. 63/479,698. The effective filing date of claims 1-20 of the instant application is 01/12/2023.
Specification
The disclosure is objected to because of the following informalities. The text of the specification is faint and blurry, rendering optical capture difficult. The specification must have text written plainly and legibly in portrait orientation and presented in a form having sufficient clarity and contrast between the paper and the writing thereon to permit the direct reproduction of readily legible copies in any number by use of photographic, electrostatic, photo-offset, and microfilming processes and electronic capture by use of digital imaging and optical character recognition. See 37 CFR 1.52(a) and (b).
Appropriate correction is required.
Claim Objections
Claims 2 and 13 are objected to because of the following informalities. The terms “Cardiovascular/Vascular” and “Traumatic Brain” need not be capitalized. In addition, the type of dementia is “Lewy body dementia” as it is disclosed at p. 19 of the instant specification. Finally, the terms “traumatic brain injury” and “frontotemporal lobe dementia” are typically used. Appropriate correction is required, although care must be taken not to add new matter.
Claim Rejections - 35 USC § 112(a)
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 1-20 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 claims contain 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.
There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is “undue.” (See In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 Fed. Cir. 1988). These factors include, but are not limited to: (a) the breadth of the claims; (b) the nature of the invention; (c) the state of the prior art; (d) the level of one of ordinary skill; (e) the level of predictability in the art; (f) the amount of direction provided by the inventor; (g) the existence of working examples; and (h) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
Claims 1-11 are drawn to a method of preventing a dementia in a patient in need thereof comprising administering a botulinum toxin to the patient by subcutaneous or intradermal injection, 1-4 units to and/or around the vicinity of a trigeminal nerve, 1-4 units to and/or around the vicinity of a cervical nerve, lateral to the patient's spine, 1-4 units to and/or around the vicinity of a thoracic nerve, lateral to the spine, 1-4 units to and/or around the vicinity of a lumbar nerve, lateral to the spine, and/or 1- 4 units to and/or around the vicinity of a sacral nerve, lateral to the spine. Claims 12-20 are also drawn to a method of preventing a dementia in a patient in need thereof comprising the same administration steps as claims 1-11, wherein a maximum total dosage of the botulinum toxin is 150 units. The patient population encompassed by the claims includes those with Alzheimer's disease, Parkinson's disease, cardiovascular/vascular dementia, Lewy body disease, Huntington's disease, traumatic brain disease, Creutzfeldt-Jakob disease, HIV-associated dementia and frontotemporal dementia.
The specification proposes a mechanism of action for how excess glutamate and or NMDA receptor dysfunction contributes to dementia by excessively stimulating neurons, causing a Ca2+ build-up of calcium ions, thereby altering intracellular pH and damaging mitochondria and leading to downstream effects resulting in neuronal loss. The specification also discloses three prophetic examples. The first prophetic example is “[a] 75-year-old male patient [who] suffers from Alzheimer's disease with minor depression who receives botulinum toxin in the area of trigeminal, cervical, thoracic, lumbar and sacral nerves…[and the] patient and his family report significant improvement in the brain function without administering medications such as Galantamine” as well as a “lower level of depression after the treatment” (see p. 36 of the instant specification). The second prophetic example is an 82-year-old female patient [who] suffers from Grade 2 Parkinson's disease with minor depression…[who] receives botulinum toxin in the area of trigeminal, cervical, thoracic, lumbar and sacral nerves…and [whose] family report[s] significant improvement in the brain function without administering medications…[and] glutamate blood levels are measured to be lower than before” (see p. 36 of the instant specification). The third prophetic example is “[a] 77-year-old female patient [who] suffers from vascular dementia…[who] receives botulinum toxin in the area of trigeminal, cervical, thoracic, lumbar and sacral nerves…[after which] glutamate blood levels are measured to be slightly lower than before” [and whose] family report[s] significant improvement in the brain function” with no worsening (see p. 37 of the instant specification). The final example concerns “[a] 62-year-old male patient [who] suffered from moderate to severe Parkinson's disease…[that has] progressed over the last 20 years…[who received] Botulinum Toxin (type A) of 12 units in the branches of the trigeminal nerve (face) and 12 units along the cervical nerves (neck)…[after which]…his tremors disappeared” (see pages 37-38 of the instant specification).
The MPEP 2164.02(I) instructs that the absence of working examples will not by itself render the invention non-enabled if the invention is otherwise disclosed in such manner that one skilled in the art will be able to practice it without an undue amount of experimentation. Nevertheless, the claims recite preventing a dementia. The term “preventing” is generally understood in the art to encompass a total protection from disease or injury. Thus, given the high level of required effect, a high level of evidence showing prevention is also required. The single working example indicates that administration of botulinum toxin to a patient with Parkinson’s results in a decline in tremors. The prophetic examples also concern patients that are already suffering from dementia, and therefore do not suggest that the claimed methods can prevent dementia from occurring.
The prior art of Blumenfeld (US 20050147626) teach the subdermal administration of about 30 units of botulinum toxin A to the locus ceruleus around the branches of the trigeminal nerve and cervical plexus, stating “[a]lthough the patient's loss of memory may not recover fully, the psychotic symptoms the patient was exhibiting can be reduced and can remain substantially alleviated for between about 2 months to about 6 months per toxin injection or for between about 1 to 5 years” (see paragraphs [0216]-[0217]). In addition, Borodic et al. (US 20160095908) teach administering botulinum toxin to patients suffering from Alzheimer’s disease, Parkinson’s disease or Huntington’s disease and has abnormal neurotransmitter activity, such as glutamate, for example (see claims; paragraphs [0041], [0045]; [0153]; [0223]). Regarding glutamate, Borodic et al. teach:
Glutamate is a neurotransmitter that exhibits endogenous neurotoxic activity that is observed in a number of neurodegenerative diseases and disorders, vascular accidents such as stroke and in seizure disorders. For example, subjects with mild to moderate dementia and probable Alzheimer's Disease have been shown to exhibit elevated levels of glutamate in the central nervous system. Elevated glutamate in the central nervous system is reflective of increased glutamatergic activity in the early stages of Alzheimer's Disease. The progressive neuronal loss observed in Alzheimer's Disease and other neurodegenerative disorders and diseases correlate with elevated glutamate and the increased excitotoxicity associated with elevated levels of this neurotransmitter.
Borodic et al. teach that botulinum toxin treatment may reduce the progression of dementia (see paragraph [0223]), but not that it can prevent dementia from occurring.
Donavan (US 6306403) discloses administering about 10-50 units of botulinum toxin to temporarily reduce dyskinesia of Parkinson's disease, the method comprising the step of intracranial administration of a botulinum toxin into a globus palladius or into a ventrolateral thalamus and also teaches that botulinum toxin blocks glutamate release (see claims 1-17; column 14, lines 11-13; column 23, lines 5-41). In summary, the specification and the prior art teach that botulinum administration to the nerves to patient’s suffering from Alzheimer’s disease and Parkinson’s disease may relieve suffering, but do not provide evidence or substantial guidance commensurate in scope with the broadly claimed “preventing a dementia”.
While the skill level in the art is high, the level of predictability is low. Even as of the filing date of this application, effective therapy for preventing dementia has eluded researchers. A review by Van Bulck et al. (Int. J. Mol. Sci. 2019, 20, 719; doi:10.3390/ ijms20030719; 36 pages total) notes that “[n]eurodegenerative diseases are incurable and debilitating conditions that result in progressive degeneration and/or death of nerve cells,” (see p. 1, 1st sentence). Van Bulck et al. note that there remains no effective treatment currently available to reverse or prevent the course of neurodegenerative diseases (see p. 2, 1st full paragraph). For instance, Lemere et al. (Rejuventation Res. 2006, 9(1):77-84) state that Alzheimer's disease is currently without an effective cure or preventive treatment (see abstract). Similarly, Hess et al. (US 20130116179) teach that the effect of the current licensed pharmaceutical therapies is to reduce symptoms rather than to prevent the development of the disease (see [0005]). Thus, the relevant art recognizes the unpredictability of methods directed to preventing Alzheimer's disease. Further, Huntington's disease is an inherited autosomal dominant disorder, and cannot be prevented, nor its course reversed or halted. See p. 1 of the website “Huntington's disease - Symptoms and causes - Mayo Clinic” (12 pages total; downloaded 06/02/2026). Prevention of dementia remains a complex endeavor that has not yet been achieved. Although the specification prophetically considers general methodologies of using the botulinum toxin in methods for prevention of dementia, the disclosure is not considered enabling for the claimed invention, since the state of the art teaches that prevention of dementia with any agent is not possible.
Due to the large quantity of experimentation necessary to determine if the claimed method can prevent dementia, the lack of direction/guidance presented in the specification regarding and the absence of working examples directed to the same, the complex and unpredictable nature of the invention as evidenced by the state of the prior art discussed above, undue experimentation would be required of the skilled artisan to make and/or use the claimed invention.
Closest Prior Art
The prior art of Blumenfeld (US 20050147626—cited above) teaches a method for treating a neurological disorder, the method comprising the step of administering a botulinum toxin sub-dermally (not intra-muscularly) to a trigeminal nerve of a patient with a neurological disorder to thereby treat and reduce the occurrence of a symptom of the neurological disorder (claims 1, 4-6), wherein the botulinum toxin is selected from the group consisting of botulinum toxin types A, B, C1, D, E, F and G (claims 2-3, 7). Blumenfeld also teaches the subdermal administration of about 30 units of botulinum toxin A to the locus ceruleus around the branches of the trigeminal nerve and cervical plexus to an Alzheimer’s patient stating “[a]lthough the patient's loss of memory may not recover fully, the psychotic symptoms the patient was exhibiting can be reduced and can remain substantially alleviated for between about 2 months to about 6 months per toxin injection or for between about 1 to 5 years” (see paragraphs [0216]-[0217]). Thus, Blumenfeld teaches methods of treating a dementia comprising the same or overlapping method steps, but not preventing a dementia.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHRISTINA M BORGEEST whose telephone number is (571)272-4482. The examiner can normally be reached M-F 9-5:30 EDT.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 5712720911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/CHRISTINA M BORGEEST/Primary Examiner, Art Unit 1675
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