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
Per Applicant’s amendment to the claims, submitted on 06/14/2024, claims 4-7, 9-10, 13-16, and 19-20 are amended, and claims 21-30 are canceled.
Priority
The instant application is a 371 of PCT/US2022/053034 filed on 12/15/2022, and claims priority to provisional application 63/290,633 filed on 12/16/2021.
Claim Rejections - 35 USC § 112 – Second 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.
Claim 13-14 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 13 is indefinite for reciting “wherein administering the effective amount of the benzoic acid salt or the prodrug thereof results in a reduction of glial inflammation, improvement in motor function or coordination, or an improvement in learning or memory dysfunction”, because a person of ordinary skill in the art would not reasonable be able to understand the metes and bounds of the claim. The instant claim does not provide any material structure to the method of the parent claim, and simply recites the result of the method of the parent claim. See MPEP2111.04:
Claim scope is not limited by claim language that suggests or makes optional but does not require steps to be performed, or by claim language that does not limit a claim to a particular structure. However, examples of claim language, although not exhaustive, that may raise a question as to the limiting effect of the language in a claim are:
(A) "adapted to" or "adapted for" clauses;
(B) "wherein" clauses; and
(C) "whereby" clauses.
The determination of whether each of these clauses is a limitation in a claim depends on the specific facts of the case. See, e.g., Griffin v. Bertina, 285 F.3d 1029, 1034, 62 USPQ2d 1431 (Fed. Cir. 2002) (finding that a "wherein" clause limited a process claim where the clause gave "meaning and purpose to the manipulative steps"). In In re Giannelli, 739 F.3d 1375, 1378, 109 USPQ2d 1333, 1336 (Fed. Cir. 2014), the court found that an "adapted to" clause limited a machine claim where "the written description makes clear that 'adapted to,' as used in the [patent] application, has a narrower meaning, viz., that the claimed machine is designed or constructed to be used as a rowing machine whereby a pulling force is exerted on the handles." In Hoffer v. Microsoft Corp., 405 F.3d 1326, 1329, 74 USPQ2d 1481, 1483 (Fed. Cir. 2005), the court held that when a "‘whereby’ clause states a condition that is material to patentability, it cannot be ignored in order to change the substance of the invention." Id. However, the court noted that a "‘whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited.’" Id. (quoting Minton v. Nat’l Ass’n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)).
Claim 14 is indefinite for reciting “wherein administering the effective amount of the benzoic acid salt or the prodrug thereof prevents or reduces the severity of a symptom associated with mental depression”, because a person of ordinary skill in the art would not reasonable be able to understand the metes and bounds of the claim. The instant claim does not provide any material structure to the method of the parent claim, and simply recites the result of the method of the parent claim. See MPEP2111.04.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-3, 5-7, 15-17, and 19-20 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tsai (US 10098861 B1).
Claim 1 recites a method of slowing the progression of or reducing the severity of a symptom associated with a nervous system injury in a subject in need thereof, the method comprising administering to the subject an effective amount of a benzoic acid salt or a prodrug thereof, thereby slowing the progression of or reducing the severity of the symptom associated with the nervous system injury.
Tsai teaches compositions comprising sodium benzoate and clozapine for the treatment of neuropsychiatric disorders (col. 1, lines 25-29)1. Tsai provides various exemplary formulations, including the following (col. 21, Table 1):
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Furthermore, Tsai indicates that neuropsychiatric disorders encompass neurological diseases, further including conditions such as demyelinating diseases, spinal cord injuries, and traumatic brain injury (col. 5-6)2 which would be considered nervous system injury. As the prior art indicates the treatment of nervous system injury by administration of a composition comprising a benzoic acid salt, Tsai is considered as anticipatory of the instant method.
Claim 2 further limits the method of claim 1 wherein the benzoic acid salt is sodium benzoate, potassium benzoate, calcium benzoate, 2-aminobenzoate, 3-aminobenzoate, 4- aminobenzoate, or any combination thereof.
As indicated in the rejection of claim 1, Tsai teaches the use of sodium benzoate.
Claim 3 further limits the method of claim 1 wherein the prodrug of the benzoic acid salt, when present, is benzyl cinnamate, glyceryl tribenzoate, cinnamic acid, benzyl acetate, benzyl alcohol, benzoic acid, quinic acid, phenylalanine, tyrosine, or any combination thereof.
As a prodrug is not explicitly present, the teachings of Tsai would anticipate the instant claim.
Claim 5 further limits the method of claim 1 wherein the subject has been diagnosed with the nervous system injury prior to the administering step.
As previously indicated, Tsai teaches the administration of their compositions for the treatment of subjects having nervous system injury. The diagnosis of such a nervous system injury (i.e., the identification of the disease/disorder), would be required for administration, otherwise a subject to be administered to would not be able to be identified. In other words, the diagnosis of the condition to be treated is inherent to the method of Tsai.
Claim 6 further limits method of claim 1 wherein the nervous system injury is a CNS injury or a peripheral nerve injury.
As previously indicated, Tsai teaches the treatment of SCI and/or TBI, each of which is considered as a CNS injury.
Claim 7 further limits the method of claim 1 wherein the nervous system injury is a spinal cord injury, spinal cord contusion, or nerve crush injury.
Tsai teaches the treatment of spinal cord injury.
Claim 9 further limits the method of claim 1 wherein the nervous system injury is TBI.
Tsai teaches the treatment of TBI.
Claim 10 further limits the method of claim 1 wherein the nervous system injury is a demyelinating disorder.
Tsai teaches the treatment of demyelinating diseases.
Claim 11 further limits the method of claim 10 wherein the demyelinating disorder is optic neuritis, X-Adrenoleukodystrophy Krabbe disease, progressive multifocal leucoencephalopathy, adrenomyeloneuropathy, acute-disseminated encephalomyelitis, acute haemorrhagic leucoencephalitis, multiple sclerosis, Balo's disease (concentric sclerosis), Charcot-Marie- Tooth disease, Guillain-Barre syndrome, HTLV-I associated myelopathy, neuromyelitis optica (Devic's disease), Schilder's disease, transverse myelitis, or a combination thereof.
Tsai teaches treatment of at least multiple sclerosis (col. 1-2)3.
Claim 15 further limits the method of claim 1 wherein the benzoic acid salt or prodrug thereof is administered as a pharmaceutical composition comprising the benzoic acid salt or prodrug thereof and a pharmaceutically acceptable excipient, wherein the composition comprises greater than 0.1% of the benzoic acid salt or prodrug by weight of the composition.
As can be seen in Table 1 of Tsai (see claim 1 rejection), the exemplary formulation comprises sodium benzoate in an amount greater than 0.1%, and excipients including boric acid or sodium alginate.
Claim 16 further limits the method of claim 1 wherein the benzoic acid salt or prodrug thereof is administered orally.
Tsai indicates that their compositions may be dosed orally, and formulated for oral administration in forms such as capsules, tablets, or others (col. 13)4.
Claim 17 recites a method of slowing the progression of or reducing the severity of a symptom associated with a nervous system injury in a subject in need thereof, the method comprising administering to the subject an effective amount of sodium benzoate, thereby slowing the progression of or reducing the severity of the symptom associated with the nervous system injury.
The instant claim appears to be reciting a method near identical to the method of claim 1, but reciting sodium benzoate rather than a benzoic acid salt. Accordingly, because Tsai teaches the use of benzoic acid, the instant claim is anticipated for the same reasons as claim 1 above.
Claim 19 further limits the method of claim 17 wherein the subject has been diagnosed with the nervous system injury prior to the administering step.
As previously indicated, Tsai teaches the administration of their compositions for the treatment of subjects having nervous system injury. The diagnosis of such a nervous system injury (i.e., the identification of the disease/disorder), would be required for administration, otherwise a subject to be administered to would not be able to be identified. In other words, the diagnosis of the condition to be treated is inherent to the method of Tsai.
Claim 20 further limits the method of claim 17 wherein the nervous system injury is a central nervous system injury or a peripheral nervous system injury.
As previously indicated, Tsai teaches the treatment of SCI and/or TBI, each of which is considered as a CNS injury.
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 4 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsai (previously referenced).
Claim 4 further limits the method of claim 1 wherein the subject has not been diagnosed with a urea cycle disorder, glycine encephalopathy, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington disease, or an autism spectrum disorder.
Tsai teaches the treatment of nervous system injury by administering compositions comprising sodium benzoate. While Tsai does not explicitly teach treatment in subjects not having diagnoses of the recited conditions, it would be obvious to treat such subjects because Tsai teaches that their compositions are useful in treating other conditions, and there would be a reasonable expectation of success in treating such conditions in subjects not having the recited conditions.
Tsai indicates that their disclosed compositions are effective for treating at least multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington disease, or autism, however it is also disclosed that said compositions are useful in the treatment of non-congenital conditions such as spinal cord injury (SCI) or traumatic brain injury (TBI). SCI and TBI are most commonly associated with acute injury, and are differentiated from the recited urea cycle disorder, glycine encephalopathy, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington disease, or an autism spectrum disorder which are considered to be congenital disorders. Absent of evidence of the contrary, it would have been obvious for a person of ordinary skill in the art to treat a subject not diagnosed with any of the recited conditions, but rather acute conditions such as SCI or TBI, using the compositions of Tsai because there would be a reasonable expectation of success in treating such acute conditions.
Claim(s) 8 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsai in view of Gao (Front Mol Neurosci. 2019 Feb 22;12:42).
Claim 8 further limits the method of claim 7 wherein the effective amount of benzoic acid salt or prodrug thereof is administered within 24 hours after the SCI, spinal cord contusion, or nerve crush injury.
As previously discussed in the rejections of claims 1 and 7, Tsai teaches the treatment of SCI by administering a composition comprising sodium benzoate and clozapine. Tsai does not explicitly teach administration within 24 hours after SCI, spinal cord contusion, or nerve crush injury. However it would be obvious to administer said composition within 24 hours of injury because Gao teaches the administration of sodium benzoate within such a timeframe, and there would be reasonable expectation that such an administration would be successful in treating the target condition.
Gao teaches the administration of sodium benzoate for the treatment of traumatic spinal cord injury (tSCI). More specifically, Gao indicates the administering of sodium benzoate to a rat model of tSCI (page 1)5. Conditions of spinal cord injury were induced by surgery (page 2)6, and animals were dosed with sodium benzoate dissolved in water at an amount of 100 mg/kg by gavage, one hour after induction of tSCI (page 2)7. The results of Gao’s testing further indicate that treatment with sodium benzoate was able increase DJ-1 expression, decrease levels of reactive oxygen species (ROS), and reverse tSCI induced neuronal apoptosis (page 12)8.
Given that Gao was successful in ameliorating SCI-associated apoptosis by administering sodium benzoate within one hour of injury, it would have been prima facie obvious for a person to combine the teachings of Tsai and Gao such that the compositions of Gao be administered within 24 hours of SCI. The combined teachings of the aforementioned would have provided a reasonable expectation that such a dosing regimen would have been successful in ameliorating or treating a symptom of SCI.
Claim(s) 12 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsai in view of Gao, and further in view of Cornelius (ANTIOXIDANTS & REDOX SIGNALING Volume 19, Number 8, 2013).
Claim 12 further limits the method of claim 9 wherein the benzoic acid salt is administered within 24 hours after the traumatic brain injury.
As previously discussed in the rejections of claims 1 and 7, Tsai teaches the treatment of SCI and TBI by administering a composition comprising sodium benzoate and clozapine. Tsai does not explicitly teach administration within 24 hours after TBI. However, it would be obvious to administer said composition within 24 hours of injury because Gao teaches the reduction of oxidative stress by administration of sodium benzoate for the treatment of SCI within such a timeframe, and Cornelius teaches that oxidative stress is a significant contributor to secondary injuries following TBI. The teachings altogether provide a reasonable expectation of success in treating symptoms of TBI induces by oxidative stress.
Gao teaches the administration of sodium benzoate for the treatment of traumatic spinal cord injury (tSCI). More specifically, Gao indicates the administering of sodium benzoate to a rat model of tSCI (page 1)9. Conditions of spinal cord injury were induced by surgery (page 2)10, and animals were dosed with sodium benzoate dissolved in water at an amount of 100 mg/kg by gavage, one hour after induction of tSCI (page 2)11. The results of Gao’s testing further indicate that treatment with sodium benzoate was able increase DJ-1 expression, decrease levels of reactive oxygen species (ROS), and reverse tSCI induced neuronal apoptosis (page 12)12.
Cornelius provides an overview on the pathology of TBI. Cornelius indicates that TBI, commonly caused by incidents of physical trauma, are followed by secondary injury. A contributor to such secondary injury being increased oxidative stress and reactive oxygen species (ROS) leading to potential neuronal death (page 836)13. Cornelius further teaches that a potential defense against increases in ROS and oxidative damage is antioxidants, which protect the brain by reducing ROS and/or inhibiting ROS formation. While the teachings of Gao are not drawn to the explicit use of antioxidants, Gao clearly indicates that sodium benzoate is capable of reducing ROS and oxidative stress by upregulating DJ-1 expression when said administration is provided within 24 hours of injury. As both the SCI taught by Gao, and the TBI taught by Cornelius are conditions brought on by primary damage (i.e., mechanical trauma), followed by shared secondary damage (i.e., oxidative damage), a person of ordinary skill would readily look towards Gao when presented with TBI as disclosed by Cornelius.
Given the teachings of each of Tsai, Gao, and Cornelius, it would have been prima facie obvious to combine the teachings of the aforementioned to arrive at the instant method. There would have been a reasonable expectation of success in reducing oxidative stress, and subsequently neuronal death, in TBI by administering the composition of Tsai to subject suffering from TBI, within 24 hours of the initial injury.
Claim(s) 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over Tsai.
Claim 18 further limits the method of claim 17 wherein the subject has not been diagnosed with a urea cycle disorder, glycine encephalopathy, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington disease, or an autism spectrum disorder.
Tsai teaches the treatment of nervous system injury by administering compositions comprising sodium benzoate. While Tsai does not explicitly teach treatment in subjects not having diagnoses of the recited conditions, it would be obvious to treat such subjects because Tsai teaches that their compositions are useful in treating other conditions, and there would be a reasonable expectation of success in treating such conditions in subjects not having the recited conditions.
Tsai indicates that their disclosed compositions are effective for treating at least multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington disease, or autism, however it is also disclosed that said compositions are useful in the treatment of non-congenital conditions such as spinal cord injury (SCI) or traumatic brain injury (TBI). SCI and TBI are most commonly associated with acute injury, and are differentiated from the recited urea cycle disorder, glycine encephalopathy, multiple sclerosis, Parkinson's disease, Alzheimer's disease, Huntington disease, or an autism spectrum disorder which are considered to be congenital disorders. Absent of evidence of the contrary, it would have been obvious for a person of ordinary skill in the art to treat a subject not diagnosed with any of the recited conditions, but rather acute conditions such as SCI or TBI, using the compositions of Tsai because there would be a reasonable expectation of success in treating such acute conditions.
Conclusion
Claims 1-20 are rejected.
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/ERIC TRAN/Examiner, Art Unit 1629
/JEFFREY S LUNDGREN/Supervisory Patent Examiner, Art Unit 1629
1 “Provided herein are pharmaceutical compositions comprising a sodium benzoate compound and clozapine; and a method for treating and/or reducing the risk of a neuropsychiatric disorder by administering such pharmaceutical composition.”
2 “The term “neuropsychiatric disorder,” including either neurological diseases or psychiatric disorders or central nervous system disorders (CNS disorders), refers to a disorder that involves either psychiatric symptoms or syndromes caused by organic central nervous system disorders… The term “neurological disease” refers to any disease of the nervous system, including diseases that involve the central nervous system (brain, brainstem, spinal cord, and cerebellum), the peripheral nervous system (including cranial nerves), and the autonomic nervous system (parts of which are located in both central and peripheral nervous system)… Examples of neurological diseases include, but are not limited to… demyelinating diseases… Further examples of neurological diseases include… spinal cord injury… traumatic brain injury…”
3 “ Target neuropsychiatric disorders include, but are not limited to… multiple sclerosis, or amyotrophic lateral sclerosis.”
4 “Solid dosage forms for oral administration include capsules, tablets, dragees, pills, powders, and granules. In such solid dosage forms, the active ingredient is mixed with at least one inert, pharmaceutically acceptable excipient or carrier…”
5 “This study aimed to explore the neuroprotective effects and mechanisms of natrium benzoate (NaB) and DJ-1 in attenuating reactive oxygen species (ROS)-induced neuronal apoptosis in traumatic spinal cord injury (t-SCI) in rats. T-SCI was induced by clip compression.”
6 “A 2-cm midline incision was made at the level of the T10 vertebra. After exposure of the lamina, laminectomy of T10 was performed to reveal the spinal cord. Next, a vascular clip (30 g force, INS 14120, Kent Scientific, Torrington, CT, United States) was used to clamp the spinal cord for 30 s without destroying the dura mater, which would cause a spinal cord compression injury (Liang et al., 2010). The sham rats were subjected to a similar surgery but without the clamp.”
7 “Natrium benzoate (100 mg/kg, Sigma-Aldrich, St. Louis, MO, United States) was dissolved in 100 µL of water and the rats were treated with NaB-containing water via gavage at 1 h after t-SCI”
8 “These results indicated that initiation of the ROS-induced apoptosis occurred after t-SCI, and DJ-1 showed preventative effects on ROS induced apoptosis and functioned as a neuroprotective protein. Treatment with NaB significantly increased the expression level of DJ-1. Moreover, NaB treatment significantly decreased the ROS level, p-p38 MAPK/p38 MAPK ratio, and CC-3 level and elevated the Bcl-2/Bax ratio. DJ-1 siRNA significantly reversed these beneficial effects. TEM analysis also revealed abnormal subcellular structures and an increased proportion of mitochondrial vacuolization in t-SCI + vehicle group, indicating that neuronal apoptosis was induced by t-SCI. NaB treatment reversed t-SCI-induced apoptosis to some extent.”
9 “This study aimed to explore the neuroprotective effects and mechanisms of natrium benzoate (NaB) and DJ-1 in attenuating reactive oxygen species (ROS)-induced neuronal apoptosis in traumatic spinal cord injury (t-SCI) in rats. T-SCI was induced by clip compression.”
10 “A 2-cm midline incision was made at the level of the T10 vertebra. After exposure of the lamina, laminectomy of T10 was performed to reveal the spinal cord. Next, a vascular clip (30 g force, INS 14120, Kent Scientific, Torrington, CT, United States) was used to clamp the spinal cord for 30 s without destroying the dura mater, which would cause a spinal cord compression injury (Liang et al., 2010). The sham rats were subjected to a similar surgery but without the clamp.”
11 “Natrium benzoate (100 mg/kg, Sigma-Aldrich, St. Louis, MO, United States) was dissolved in 100 µL of water and the rats were treated with NaB-containing water via gavage at 1 h after t-SCI”
12 “These results indicated that initiation of the ROS-induced apoptosis occurred after t-SCI, and DJ-1 showed preventative effects on ROS induced apoptosis and functioned as a neuroprotective protein. Treatment with NaB significantly increased the expression level of DJ-1. Moreover, NaB treatment significantly decreased the ROS level, p-p38 MAPK/p38 MAPK ratio, and CC-3 level and elevated the Bcl-2/Bax ratio. DJ-1 siRNA significantly reversed these beneficial effects. TEM analysis also revealed abnormal subcellular structures and an increased proportion of mitochondrial vacuolization in t-SCI + vehicle group, indicating that neuronal apoptosis was induced by t-SCI. NaB treatment reversed t-SCI-induced apoptosis to some extent.”
13 “Further, we tried to clarify that the role of oxidative damage may be toxic to neuronal cells, examining the nature of the reactive species involved in TBI, and showing how different classes of anti-oxidant are implicated in the literature with beneficial effects on amelioration of damage after TBI.”
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