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 and Response to Restriction Requirement
Claims 1-20 are pending as of the response filed 02/08/2026. Applicant’s election of a species of isoquinoline derivative being administered to treat a patient at risk of disturbed cerebral homeostasis as fasudil hydrochloride is acknowledged. Claims 1-14, 16, 18, and 20 encompass the elected species. Claims 15, 17 and 19 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected species, there being no allowable generic or linking claim. Claims 1-14, 16, 18, and 20 are examined herein.
Priority
This application is a CON of 18/047,276 filed 10/18/2022 PAT 11738030. Accordingly, claims 1-14, 16, 18, and 20 have an effective filing date of 10/18/2022, the filing date of the parent application.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code on Para. [0061] of the instant specification. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Rejections - 35 USC § 112 – Written Description
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 1-14 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 written description requirement. The claim contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claim 1 is drawn to a method of treating a patient at risk of disturbed cerebral homeostasis: wherein said method comprises administering to said patient an isoquinoline derivative that regulates vascular activity by modulating rho-associated coiled-coil containing kinase activity. The instant specification at Para. [0045] defines the term "derivative" as a broad term that refers without limitation to any compound as described herein incorporating one or more derivative groups, or being substituted by or functionalized to include one or more derivative groups. Derivatives include but are not limited to esters, amides, anhydrides, acid halides, thioesters, phosphates, triphosphates, and β-sulfenyl derivatives. Moreover, Para. [0139] of the instant specification references various compounds listed in several patent documents as nonlimiting examples of isoquinoline derivatives. While these are suggested functional groups and/or examples for the isoquinoline derivative, the specification does not list all possible derivatives that fall under the definition of the term “derivative”. The specification does not clearly define how far reaching or to what extent an isoquinoline compound can be modified and still be considered a derivative that would modulate rho-associated coiled-coil containing kinase activity. Therefore, the scope of the isoquinoline derivative compounds encompassed by the claims is extremely broad and includes species that do not share both a substantial structural feature and a common function that flows from the substantial feature. The myriad of functional groups that can be added to derivatize the isoquinoline compounds would be presumed by one of ordinary skill in the art to have different physical and chemical properties that would lead to different biological activities.
However, the specification does not provide a reasonably representative disclosure of the isoquinoline derivative compounds encompassed by the claims. The specification, at best, discloses hydroxyfasudil, fasudil and fasudil hydrochloride in the studies done on rats, Examples 1-2 (Paras. [0267]-[0276]) and the remaining prophetic Examples 3-5 (Paras. [0277]-[0287]) described in the specification. These are not viewed as being reasonably representative of the genus of isoquinoline derivative compounds in its claimed scope because no readily apparent combination of identifying characteristics is provided, other than the disclosure of those specific species as examples of the claimed genus. It is not readily apparent that the genus of compounds claimed have a structural entity in common, that leads to their rho-associated coiled-coil containing kinase modulating activity.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. Whether the specification shows that the inventor was in possession of the claimed invention is not a single, simple determination, but rather is a factual determination reached by considering a number of factors. Factors to be considered in determining whether there is sufficient evidence of possession include the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient. See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. See MPEP 2163 (II) 3 (a) (i).
A chemical genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. If the genus has substantial variance, the disclosure must describe a sufficient number of species to reflect the variation within that genus. The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice (see i)(A) above), reduction to drawings (see i)(B) above), or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus (see i)(C) above). See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See AbbVie Deutschland GmbH & Co., KG v. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014). The disclosure of only one species encompassed within a genus adequately describes a claim directed to that genus only if the disclosure "indicates that the patentee has invented species sufficient to constitute the gen[us]." See Enzo Biochem, 323 F.3d at 966, 63 USPQ2d at 1615. "A patentee will not be deemed to have invented species sufficient to constitute the genus by virtue of having disclosed a single species when … the evidence indicates ordinary artisans could not predict the operability in the invention of any species other than the one disclosed. See MPEP 2163 (II) 3 (a) (ii).
In the instant case, there is no evidence Applicants had possession of the full genus of isoquinoline derivative compounds at the time of filing, because the specification does not conclusively demonstrate the structure-activity relationship of the claimed vast array of compounds, towards their rho-associated coiled-coil containing kinase modulating activity. The instant specification does not describe enough species of compounds having the rho-associated coiled-coil containing kinase modulating function within the scope of the claimed invention. Thus, the written description requirement for the claimed genus of compounds has not been met.
In response to this rejection, the Applicant can amend the claim(s) to recite only individual species or grouping of species that share a substantial structure as well as a common function that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claim(s) in fact share a common function that flows from the substantial structural feature.
Claims 2-14 depend from the rejected base claim and are similarly rejected.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1-14 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.
Regarding instant claim 1, the claim recites the phrase “an isoquinoline derivative that regulates vascular activity by modulating rho-associated coiled-coil containing kinase activity”. The instant specification at Para. [0045] states the term "derivative" is a broad term and refers without limitation to any compound as described herein incorporating one or more derivative groups, or being substituted by or functionalized to include one or more derivative groups. Derivatives include but are not limited to esters, amides, anhydrides, acid halides, thioesters, phosphates, triphosphates, and β-sulfenyl derivatives. Moreover, Para. [0139] of the instant specification references various compounds listed in several patent documents as nonlimiting examples of isoquinoline derivatives. While these are suggested functional groups and examples for the isoquinoline derivative, the specification do not list all possible derivatives that fall under the definition of the term “derivative”. The full scope of the compounds encompassed by the claim has not been defined. Therefore the metes and bounds of the claim are indefinite.
For the purpose of applying prior art, claim 1 has been interpreted to include the functional groups esters, amides, anhydrides, acid halides, thioesters, phosphates, triphosphates, and β-sulfenyl groups as constituting the isoquinoline derivatives.
Claims 2-14 depend either directly or indirectly from claim 1, and are similarly rejected.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Li et al. (Hydrochloride fasudil attenuates brain injury in ICH rats, 2020, hereinafter Li, in the IDS).
Regarding instant claim 1, Li teaches administering hydrochloride fasudil (HF) (i.e., the instantly elected species of an isoquinoline derivative) in rats following intracerebral hemorrhage (ICH) (i.e., a condition that puts the subject at risk of severe disruption of cerebral homeostasis) (Abstract). Li teaches the levels of Rho-associated protein kinases (ROCK2) were significantly lower in rats treated with HF than in controls (Abstract). Li teaches the administration of HF significantly reduced the levels of inflammatory cytokines and brain water content from day 1 to day 7 (Abstract). Li teaches ICH is an acute cerebrovascular disease (Pg. 75, second column, last paragraph). Li teaches ROCK2 regulate a variety of cell functions and play key roles in cell contraction, inflammation, vascular leakage, and maintenance of the blood–brain barrier (Pg. 76, first column, first full paragraph).
According to MPEP 2112.01(II), “Products of identical chemical composition can not have mutually exclusive properties.” Any properties exhibited by or benefits from are not given any patentable weight over the prior art provided the composition is inherent. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the disclosed properties are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ 1655, 1658 (Fed. Cir. 1990).
In the instant case hydrochloride fasudil, a Rho-kinase inhibitor (specifically, a ROCK2 inhibitor), by virtue of its inherent property, is capable of regulating vascular activity.
Therefore, the disclosure of Li anticipates the method of instant claim 1, by regulating vascular activity.
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.
Claim 1 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Zhao et al. (Effect of Fasudil Hydrochloride, a Protein Kinase Inhibitor, on Cerebral Vasospasm and Delayed Cerebral Ischemic Symptoms After Aneurysmal Subarachnoid Hemorrhage - Results of a Randomized Trial of Fasudil Hydrochloride Versus Nimodipine, 2006, hereinafter Zhao, in the IDS).
Regarding instant claim 1, Zhao teaches the efficacy and safety of fasudil hydrochloride) (i.e., the instantly elected species of an isoquinoline derivative), a novel protein kinase inhibitor, for the treatment of cerebral vasospasm and associated cerebral ischemic symptoms in patients with ruptured cerebral aneurysm (i.e., a condition that puts the subject at risk of severe disruption of cerebral homeostasis) in comparison to nimodipine (Abstract). Zhao teaches patients were administered 30 mg of fasudil hydrochloride by intravenous injection over a period of 30 minutes three times a day that resulted in inhibitory effects on cerebral vasospasm (Abstract; Pg. 423, first column, last paragraph). Zhao teaches fasudil hydrochloride is a safe and efficient agent for suppressing cerebral vasospasm after subarachnoid hemorrhage surgery for ruptured cerebral aneurysm (Abstract; Pg. 425, first column, last paragraph – second column, continued paragraph; Pg. 426, first column, last paragraph). Zhao teaches fasudil hydrochloride is a new potent vasodilator and is a Rho protein kinase inhibitor (Pg. 422, first column, last paragraph). Zhao teaches fasudil hydrochloride suppresses cerebral vasospasm after subarachnoid hemorrhage surgery, alleviates subsequent cerebral ischemia by improving hemodynamic functions (Pg. 422, first column, last paragraph).
According to MPEP 2112.01(II), “Products of identical chemical composition can not have mutually exclusive properties.” Any properties exhibited by or benefits from are not given any patentable weight over the prior art provided the composition is inherent. A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the disclosed properties are necessarily present. In re Spada, 911 F.2d 705, 709, 15 USPQ 1655, 1658 (Fed. Cir. 1990).
Therefore, the disclosure of Zhao anticipates the method of instant claim 1, by regulating vascular activity.
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.
Claims 2-3 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (Effect of Fasudil Hydrochloride, a Protein Kinase Inhibitor, on Cerebral Vasospasm and Delayed Cerebral Ischemic Symptoms After Aneurysmal Subarachnoid Hemorrhage - Results of a Randomized Trial of Fasudil Hydrochloride Versus Nimodipine, 2006, hereinafter Zhao, in the IDS) as applied to claim 1 above.
The teachings of Zhao are set forth in the anticipation rejection above and incorporated herein by reference.
Regarding instant claims 2-3, Zhao anticipates the method of instant claim 1.
Zhao does not teach wherein said patient is determined to be intolerant of nimodipine OR wherein said patient has developed dose-limiting hypotension in response to nimodipine.
Zhao teaches administering either 30 mg of fasudil hydrochloride by intravenous injection over a period of 30 minutes three times a day or 1 mg/hr of nimodipine by continuous intravenous infusion (Abstract; Pg. 423, first column, last paragraph). Zhao teaches both fasudil hydrochloride and nimodipine showed inhibitory effects on cerebral vasospasm (Abstract; Table 3). Zhao teaches that there was a slight decrease in the systolic pressure in the fasudil group and a slight decrease in systolic and diastolic pressure in the nimodipine group (Pg. 425, first column, last paragraph – second column, continued paragraph). Zhao teaches drug administration was not stopped in the fasudil group due to decreased blood pressure, whereas drug administration was stopped in one patient in the nimodipine group due to decreased blood pressure (Pg. 425, first column, last paragraph – second column, continued paragraph) (i.e., the patient developed a dose-limiting side effect to nimodipine OR inability to tolerate a standard dose). Zhao teaches an overall lower incidence (35.1%) of adverse reactions in patients in the fasudil group versus the incidence (42.9%) of adverse reactions in patients in the nimodipine group (Pg. 425, second column, first full paragraph). Zhao teaches fasudil hydrochloride improved motor disturbance more than nimodipine (Abstract; Table 2) and fasudil hydrochloride has a protective effect on the anoxic neurodegeneration of neuronal cells (Pg. 422, first column, last paragraph). Zhao teaches patients in the fasudil group (69.7%) showed good recovery 1 month after subarachnoid hemorrhage versus nimodipine (55.9%) (Table 6).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention, in view of the teachings of Zhao to have applied the method of Zhao in the treatment of a patient at risk of disturbed cerebral homeostasis who is determined to be intolerant of nimodipine OR a patient who has developed dose-limiting hypotension in response to nimodipine, with a reasonable expectation of success. Zhao teaches the efficacy and safety of fasudil hydrochloride (i.e., the instantly elected species of an isoquinoline derivative), a novel protein kinase inhibitor, for the treatment of cerebral vasospasm and associated cerebral ischemic symptoms in patients with ruptured cerebral aneurysm (i.e., a condition that puts the subject at risk of severe disruption of cerebral homeostasis) in comparison to nimodipine. Zhao teaches that there was a slight decrease in the systolic pressure in the fasudil group and a slight decrease in systolic and diastolic pressure in the nimodipine group. Zhao teaches drug administration was not stopped in the fasudil group due to decreased blood pressure, whereas drug administration was stopped in one patient in the nimodipine group due to decreased blood pressure. Zhao teaches various advantages of fasudil hydrochloride versus nimodipine in the treatment of subarachnoid hemorrhage – the fasudil group showed overall lower incidence of adverse reactions (35.1%) versus nimodipine (42.9%), the fasudil group showed improved motor disturbance than nimodipine, and the fasudil group (69.7%) showed good recovery 1 month after subarachnoid hemorrhage versus nimodipine (55.9%).
Therefore, one of ordinary skill in the art would have been motivated to treat this sub-population of patients, i.e., a patient determined to be intolerant of nimodipine OR a patient who has developed dose-limiting hypotension in response to nimodipine with the method of Zhao, with a reasonable expectation of success in treating such a condition. The motivation being to improve the functional prognosis of these patients (Pg. 426, first column, last paragraph).
Therefore, the teachings of Zhao render the limitations of instant claims 2-3 prima facie obvious.
Claims 4, 7, 11-12, 14, 16, 18 and 20 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (Effect of Fasudil Hydrochloride, a Protein Kinase Inhibitor, on Cerebral Vasospasm and Delayed Cerebral Ischemic Symptoms After Aneurysmal Subarachnoid Hemorrhage - Results of a Randomized Trial of Fasudil Hydrochloride Versus Nimodipine, 2006, hereinafter Zhao, in the IDS) as applied to claim 1-3 above, and further in view of Barry et al. (New therapeutic approaches to subarachnoid hemorrhage, 25 April 2012, hereinafter Barry).
The teachings of Zhao are set forth in the obviousness rejection above and incorporated herein by reference.
Regarding instant claims 4, 11, 14, 16 and 20, Zhao renders the method of instant claim 2, prima facie obvious. Zhao do not teach wherein said disturbed cerebral homeostasis comprises abnormal ICP; wherein said disturbed cerebral homeostasis follows a brain injury that deposits blood in the subarachnoid space.
Barry teaches that early mechanisms of secondary brain injury precede the delayed vasospasm phase and contribute to the poor outcome following subarachnoid hemorrhage (SAH) (Abstract). Barry teaches SAH involves high intracranial pressure (ICP) (i.e., abnormal ICP), low cerebral perfusion pressure (CPP), acute vasospasm, disturbed cerebral autoregulation, cerebral edema, oxidative stress, seizures, microvascular damage and hyperglycemia (Abstract). Barry teaches following SAH increased arterial blood pressure in response to raised ICP associated with the initial bleed may contribute to rebleeding (Pg. 846, first column, second full paragraph) (i.e., the ICP follows brain injury that deposits blood in the subarachnoid space). Barry teaches raised ICP following SAH is primarily caused by the volume of extravasated blood within the confines of the rigid skull (Pg. 846, first column, last paragraph – second column, continued paragraph). Barry teaches agents that simultaneously target vasospasm and other secondary injury factors show particular promise (Pg. 846, Article Highlights inset, last bullet). Barry teaches delayed vasospasm may be a marker of ongoing secondary brain injury and that agents that attenuate vasospasm also affect multiple secondary injury pathways (Pg. 853, first column, last paragraph – second column, continued paragraph). Barry teaches fasudil has shown benefit in treating refractory vasospasm and reduced incidence of symptomatic and angiographic cerebral vasospasm, reduced incidence of cerebral infarction and improved patient outcomes (Pg. 850, second column, first full paragraph).
Therefore, in the absence of evidence to the contrary, the method of Zhao when practiced in treating a subject with SAH (i.e., a condition with disturbed cerebral homeostasis) who is determined to be intolerant of nimodipine would have necessarily treated abnormal ICP that precedes delayed vasospasm in SAH.
Regarding instant claims 7, 12 and 18, Zhao renders the method of instant claim 3, prima facie obvious. Zhao do not teach wherein said disturbed cerebral homeostasis comprises abnormal ICP; wherein said disturbed cerebral homeostasis follows a brain injury that deposits blood in the subarachnoid space.
Barry teaches that early mechanisms of secondary brain injury precede the delayed vasospasm phase and contribute to the poor outcome following subarachnoid hemorrhage (SAH) (Abstract). Barry teaches SAH involves high intracranial pressure (ICP) (i.e., abnormal ICP), low cerebral perfusion pressure (CPP), acute vasospasm, disturbed cerebral autoregulation, cerebral edema, oxidative stress, seizures, microvascular damage and hyperglycemia (Abstract). Barry teaches following SAH increased arterial blood pressure in response to raised ICP associated with the initial bleed may contribute to rebleeding (Pg. 846, first column, second full paragraph) (i.e., the ICP follows brain injury that deposits blood in the subarachnoid space). Barry teaches raised ICP following SAH is primarily caused by the volume of extravasated blood within the confines of the rigid skull (Pg. 846, first column, last paragraph – second column, continued paragraph). Barry teaches agents that simultaneously target vasospasm and other secondary injury factors show particular promise (Pg. 846, Article Highlights inset, last bullet). Barry teaches delayed vasospasm may be a marker of ongoing secondary brain injury and that agents that attenuate vasospasm also affect multiple secondary injury pathways (Pg. 853, first column, last paragraph – second column, continued paragraph). Barry teaches fasudil has shown benefit in treating refractory vasospasm and reduced incidence of symptomatic and angiographic cerebral vasospasm, reduced incidence of cerebral infarction and improved patient outcomes (Pg. 850, second column, first full paragraph).
Therefore, in the absence of evidence to the contrary, the method of Zhao when practiced in treating a subject with SAH (i.e., a condition with disturbed cerebral homeostasis) who has developed dose-limiting hypotension in response to nimodipine would have necessarily treated abnormal ICP that precedes delayed vasospasm in SAH.
Claims 5-6 and 8-9 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (Effect of Fasudil Hydrochloride, a Protein Kinase Inhibitor, on Cerebral Vasospasm and Delayed Cerebral Ischemic Symptoms After Aneurysmal Subarachnoid Hemorrhage - Results of a Randomized Trial of Fasudil Hydrochloride Versus Nimodipine, 2006, hereinafter Zhao, in the IDS) as applied to claim 1-3 above, and further in view of Sriram et al. (Neuroinflammation and subarachnoid hemorrhage: a revised look at the literature, 01 July 2022, hereinafter Sriram).
The teachings of Zhao are set forth in the obviousness rejection above and incorporated herein by reference.
Regarding instant claims 5-6, Zhao renders the method of instant claim 2, prima facie obvious. Zhao do not teach wherein said disturbed cerebral homeostasis comprises hydrocephalus; wherein said disturbed cerebral homeostasis comprises acute CNS neuroinflammation.
Sriram teaches that neuroinflammation is implicated in aneurysmal subarachnoid hemorrhage (Abstract). Sriram teaches perpetual neuroinflammation can contribute to vasospasm and hydrocephalus (Abstract).
Therefore, in light of the teachings Sriram, it is prima facie obvious that the disturbed cerebral homeostasis of Zhao comprises hydrocephalus and/or acute CNS neuroinflammation.
Regarding instant claims 8-9, Zhao renders the method of instant claim 3, prima facie obvious. Zhao do not teach wherein said disturbed cerebral homeostasis comprises hydrocephalus; wherein said disturbed cerebral homeostasis comprises acute CNS neuroinflammation.
Sriram teaches that neuroinflammation is implicated in aneurysmal subarachnoid hemorrhage (Abstract). Sriram teaches perpetual neuroinflammation can contribute to vasospasm and hydrocephalus (Abstract).
Therefore, in light of the teachings Sriram, it is prima facie obvious that the disturbed cerebral homeostasis of Zhao comprises hydrocephalus and/or acute CNS neuroinflammation.
Claims 10 and 13 are rejected under 35 U.S.C. 103 as being unpatentable over Zhao et al. (Effect of Fasudil Hydrochloride, a Protein Kinase Inhibitor, on Cerebral Vasospasm and Delayed Cerebral Ischemic Symptoms After Aneurysmal Subarachnoid Hemorrhage - Results of a Randomized Trial of Fasudil Hydrochloride Versus Nimodipine, 2006, hereinafter Zhao, in the IDS) as applied to claim 1-3 above and further in view of Nonaka et al. (Intra-arterial Injection of Fasudil Hydrochloride for Cerebral Vasospasm Secondary to Bacterial Meningitis, 13 September 2018, hereinafter Nonaka, in the IDS).
The teachings of Zhao are set forth in the obviousness rejection above and incorporated herein by reference.
Regarding instant claim 10, Zhao renders the method of instant claim 2, prima facie obvious. Zhao do not teach wherein said disturbed cerebral homeostasis follows meningitis.
Nonaka teaches cerebral vasospasm secondary to bacterial meningitis is relatively rare and difficult to treat (Abstract). Nonaka teaches intra-arterial infusion of fasudil hydrochloride was an effective treatment for cerebral vasospasm secondary to bacterial meningitis (Abstract; Pg. 91, second column, first full paragraph – second full paragraph). Nonaka teaches bacterial meningitis are often affected by intracranial consequences, such as cerebral edema, hydrocephalus, and cerebrovascular complications (i.e., disturbed cerebral homeostasis).
Therefore, in light of the teachings Nonaka, one of ordinary skill in the art would have been motivated to treat disturbed cerebral homeostasis that follows meningitis using the method of Zhao, with a reasonable expectation of success. The motivation being to use a safer alternative to balloon angioplasty in the treatment of cerebral vasospasm secondary to bacterial meningitis (Nonaka, Pg. 93, first column, last paragraph).
Regarding instant claim 13, Zhao renders the method of instant claim 2, prima facie obvious. Zhao do not teach wherein said abnormal ICP follows meningitis.
Nonaka teaches cerebral vasospasm secondary to bacterial meningitis is relatively rare and difficult to treat (Abstract). Nonaka teaches intra-arterial infusion of fasudil hydrochloride was an effective treatment for cerebral vasospasm secondary to bacterial meningitis (Abstract; Pg. 91, second column, first full paragraph – second full paragraph). Nonaka teaches bacterial meningitis are often affected by intracranial consequences, such as cerebral edema, hydrocephalus, and cerebrovascular complications (i.e., cerebral edema and hydrocephalus result in abnormal ICP). Nonaka teaches ventricular drainage was performed on postoperative day 17 because of hydrocephalus (Fig. 1D) (i.e., a procedure that relieves ICP).
Therefore, in light of the teachings Nonaka, one of ordinary skill in the art would have been motivated to treat disturbed cerebral homeostasis that follows meningitis (wherein abnormal ICP follows meningitis) using the method of Zhao, with a reasonable expectation of success. The motivation being to use a safer alternative to balloon angioplasty in the treatment of cerebral vasospasm secondary to bacterial meningitis (Nonaka, Pg. 93, first column, last paragraph).
Double Patenting
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 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); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
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 nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-14, 16, 18 and 20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 and 5 of U.S. Patent No. 11,738,030 B2 in view of Nonaka et al. (Intra-arterial Injection of Fasudil Hydrochloride for Cerebral Vasospasm Secondary to Bacterial Meningitis, 13 September 2018, hereinafter Nonaka, in the IDS).
Although the claims at issue are not identical, they are not patentably distinct from each other because both set of claims are drawn to a method of treating a patient at risk of/ experiencing disturbed cerebral homeostasis wherein said method comprises administering to said patient an isoquinoline derivative.
The instant claims are drawn to a method of treating a patient at risk of disturbed cerebral homeostasis: wherein said method comprises administering to said patient an isoquinoline derivative that regulates vascular activity by modulating rho-associated coiled-coil containing kinase activity.
The claims of the reference ‘030 patent are drawn to the following.
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The method of the reference ‘030 patent anticipates a method of treating a patient at risk of disturbed cerebral homeostasis, since the reference patent teaches administering fasudil hydrochloride as the active agent to said subject, which is a species of isoquinoline derivative (a species anticipates a claim to a genus). Both involve the same active step. Moreover, claim 1 and 5 of the reference ‘030 patent anticipates the limitations of instant claims 1-9, 11-12, 14, 16, 18 and 20.
The claims of the ‘030 patent do not teach wherein said disturbed cerebral homeostasis follows meningitis; wherein said abnormal ICP follows meningitis.
Nonaka teaches cerebral vasospasm secondary to bacterial meningitis is relatively rare and difficult to treat (Abstract). Nonaka teaches intra-arterial infusion of fasudil hydrochloride was an effective treatment for cerebral vasospasm secondary to bacterial meningitis (Abstract; Pg. 91, second column, first full paragraph – second full paragraph). Nonaka teaches bacterial meningitis are often affected by intracranial consequences, such as cerebral edema, hydrocephalus, and cerebrovascular complications (i.e., cerebral edema and hydrocephalus result in abnormal ICP). Nonaka teaches ventricular drainage was performed on postoperative day 17 because of hydrocephalus (Fig. 1D) (i.e., a procedure that relieves ICP).
Therefore, in light of the teachings of the ‘030 patent and Nonaka, one of ordinary skill in the art would have been motivated to treat disturbed cerebral homeostasis that follows meningitis (wherein abnormal ICP follows meningitis), to arrive at the method of the instant claims.
The instant claims 1-14, 16, 18 and 20 and claims 1 and 5 of U.S. Patent No. 11,738,030 B2 are therefore not patentably distinct.
This is a nonstatutory double patenting rejection.
Conclusion
Claims 1-14, 16, 18 and 20 are rejected.
No claims are allowed.
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/PADMAJA S RAO/Examiner, Art Unit 1627
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