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 .
DETAILED ACTION
1. Claims 1-18 are currently pending and under examination.
Priority
2. Acknowledgment is made of Applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d). The certified copy has been filed in parent Application No. 16/766,338, filed on May 22, 2020.
Information Disclosure Statement
3. The information disclosure statement (IDS) submitted on February 3, 2025 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner. An initialed copy is attached hereto.
Claim Objections
4. Claims 7 and 17 are objected to because of the following informalities: Said claims recite both “1191l” and “1191L”. If in deed “1191l” is really “1191L” it is a duplicate within the same claim. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
5. Claims 1-18 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(s) 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.
The claimed invention is drawn to a method for treating an autonomic disorder in a human patient in need thereof, the method comprising administering to the patient a clostridial neurotoxin comprising an HCC domain from a BoNT/B, BoNT/F, BoNT/D, BoNT/D-C, or BoNT/G; wherein said autonomic disorder is selected from: a. a smooth muscle disorder selected from: i. a urinary disorder selected from bladder spasms, detrusor-sphincter dyssynergia (DSD), urinary retention, nocturia, urge incontinence and urinary frequency; ii. a gastrointestinal disorder selected from sphincter of Oddi dysfunction, esophageal spasms, intestinal spasms, gastroparesis, constipation, occasional diarrhea, and oropharyngeal dysphasia; iii. a vascular or cardiovascular disorder; and iv. a sexual disorder; b. a hypersecretory disorder selected from gustatory sweating, crocodile tears syndrome, excessive mucus secretion, and bromhidrosis; c. an inflammatory disorder with an autonomic component; d. a neuroendocrine disorder; and e. an autonomic disorder associated with a central neurological disorder having cerebellar/pyramidal features.
To fulfill the written description requirements set forth under 35 USC § 112, first paragraph, the specification must 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 fully describe the method as claimed. In the instant case, to fulfill the written description requirement, the genus of autonomic disorders to be treated in a subject must be adequately described. The claim overall is a broad claim in terms of patient population.
The specification really only focuses on and describes studies of the human bladder tissue samples. Briefly, human bladder tissue samples were obtained from patients undergoing cystectomy for bladder cancer with no known bladder dysfunction. After surgical procedure, the samples were immediately transported from the operating room to the pathologist facilities where a normal piece of the bladder dome, i.e. with no macroscopic tumoral tissue, was selected for experiments. Urothelium was carefully removed and eight sections of detrusor were excised from the bladder of each donor for each experiment.
Following the equilibration period, the detrusor smooth muscle strips were primed by adding sequentially to the organ bath KCl (100 mM, 10 min) then carbachol (3.10−6 M, 10 min) with washing steps between each compound addition. An injection of 0.5% of gelatin was then performed into the organ bath prior to the application of EFS trains. EFS trains were continuously performed by groups of 3 stimulations applied at 1-min interval and followed by a 3-min period of rest (conditions of stimulation based on our experience with human bladder tissue and selected to give robust and stable contractions in human bladder strips). Stimulations were continued until stable responses were obtained (a response was considered stable when the percentage of variation of the amplitude of EFS contractions calculated for the last three groups of EFS contraction during stabilization period was ≥90% or ≤110%).
Individual strips were incubated with vehicle (Krebs with 0.5% gelatin), 0.1, 1, 3, 5 or 10 nM of a botulinum neurotoxin and the EFS stimulations were continued for 3 hours. At the end of the experiment, bladder strips were contracted by direct activation of the muscarinic receptor by adding carbachol (3.10−6 M, 10 min) to the organ bath. The comparison of carbachol-induced strip contractions before and after botulinum neurotoxins incubation acts as a viability test of the strips during the experiment (Specifications paragraphs 0239-0246).
The specification, however, does not adequately describe the method as claimed, particularly methods of treating any autonomic disorder selected from: a. a smooth muscle disorder selected from: i. a urinary disorder selected from bladder spasms, detrusor-sphincter dyssynergia (DSD), urinary retention, nocturia, urge incontinence and urinary frequency; ii. a gastrointestinal disorder selected from sphincter of Oddi dysfunction, esophageal spasms, intestinal spasms, gastroparesis, constipation, occasional diarrhea, and oropharyngeal dysphasia; iii. a vascular or cardiovascular disorder; and iv. a sexual disorder; b. a hypersecretory disorder selected from gustatory sweating, crocodile tears syndrome, excessive mucus secretion, and bromhidrosis; c. an inflammatory disorder with an autonomic component; d. a neuroendocrine disorder; and e. an autonomic disorder associated with a central neurological disorder having cerebellar/pyramidal features. Further, the specification does not demonstrate that said disorders, once a human patient is administered any clostridial neurotoxin comprising an HCC domain from a BoNT/B, BoNT/F, BoNT/D, BoNT/D-C, or BoNT/G, are treated with success.
The written description requirement may be satisfied through sufficient description of a representative number of species by actual reduction to practice, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, structure or other physical and/or chemical properties, by functional characteristics coupled with a known or teach correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the Applicant was in possession of the claimed invention.
Finally, University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that: ...To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines Inc. , 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (" [T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2datl966.
Written description requirement must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the "written description" inquiry, whatever is now claimed. The Guidelines further state, "[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus" (Id. at 1106); accordingly, it follows that an adequate written description of a genus cannot be achieved in the absence of a disclosure of at least one species within the genus.
Therefore, absent a detailed and particular description the skilled artisan could not immediately recognize or distinguish members of the claimed method. Therefore, because the art is unpredictable, in accordance with the Guidelines, the description do not meet the written description requirements.
Claim Rejections - 35 USC § 112
Improper Markush Grouping
6. Claims 1-10 are rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of disorders is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the stated disorders are selected from autonomic disorders, smooth muscle disorders, vascular and cardiovascular disorders, sexual disorders, hypersecretory disorders, inflammatory disorders, neuroendocrine disorders and autonomic disorders associated with central neurological disorders having cerebellar/pyramidal features; and these disorders do not both share a single structural similarity and a common use.
The autonomic nervous system regulates the function of the body’s internal organs, such as heart rate, blood pressure, digestion, and body temperature. People with an autonomic disorder have trouble regulating one or more of these systems, which can result in fainting, lightheadedness, fluctuating blood pressure, and other symptoms.
Inflammatory disease happens when your body's immune system mistakenly attacks healthy cells, causing lasting pain, swelling, and tissue damage. Common examples include rheumatoid arthritis, inflammatory bowel disease (IBD), and asthma.
Sexual disorders, or sexual dysfunctions, involve problems during any phase of the sexual response cycle—including desire, arousal, orgasm, and pain. Cardiovascular disease is a group of conditions affecting the heart or blood vessels, most commonly including coronary artery disease, high blood pressure, and stroke. It is the leading cause of death worldwide, often driven by fatty plaque buildup inside the arteries that restricts blood flow.
Neuroendocrine disorders occur when the complex communication system between the nervous and endocrine systems breaks down, causing the body to produce too many or too few hormones. This broad category includes conditions like inherited genetic syndromes (e.g., MEN1) and neuroendocrine tumors (NETs), which can arise anywhere in the body.
As demonstrated by the described disorders above, said conditions and disorders do not share both a single structural similarity and a common use. To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
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.
7. Claim(s) 1-8 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Dong et al., WO 2013/180799 A1; Published: 12/5/13.
Independent claim 1 is drawn to a method for treating an autonomic disorder in a human patient in need thereof, the method comprising administering to the patient a clostridial neurotoxin comprising an HCC domain from a BoNT/B, BoNT/F, BoNT/D, BoNT/D-C, or BoNT/G; wherein said autonomic disorder is selected from:
a. a smooth muscle disorder selected from:
i. a urinary disorder selected from bladder spasms, detrusor-sphincter dyssynergia (DSD), urinary retention, nocturia, urge incontinence and urinary frequency;
ii. a gastrointestinal disorder selected from sphincter of Oddi dysfunction, esophageal spasms, intestinal spasms, gastroparesis, constipation, occasional diarrhoea, and oropharyngeal dysphasia;
iii. a vascular or cardiovascular disorder; and
iv. a sexual disorder;
b. a hypersecretory disorder selected from gustatory sweating, crocodile tears syndrome, excessive mucus secretion, and bromhidrosis;
c. an inflammatory disorder with an autonomic component;
d. a neuroendocrine disorder; and
e. an autonomic disorder associated with a central neurological disorder having cerebellar/pyramidal features.
Dong relates to a method for treating a condition associated with unwanted neuronal activity comprising administering a therapeutically effective amount of the BoNT polypeptide to a subject to thereby contact one or more neurons exhibiting unwanted neuronal activity, to thereby treat the condition. The condition is selected from the group consisting of laryngeal dystonia, oromandibular dysphonia, lingual dystonia, cervical dystonia, focal hand dystonia, blepharospasm, strabismus, hemifacial spasm, eyelid disorder, cerebral palsy, focal spasticity and other voice disorders, spasmodic colitis, neurogenic bladder (includes frequent urination), anismus, limb spasticity, tics, tremors, bruxism, anal fissure, achalasia, dysphagia and other muscle tone disorders and other disorders characterized by involuntary movements of muscle groups, lacrimation, hyperhidrosis, excessive salivation, excessive gastrointestinal secretions, secretory disorders, pain from muscle spasms, headache pain, and dermatological or aesthetic/cosmetic conditions (see paragraph 0022; meets claim 1-3).
Moreover, Dong discloses that BoNT/B-Hc has one or more substitution mutation (e.g., at positions which correspond to positions E 1191 , S 1199, S 1201 , V 1118, P 1117, Y 1183 , Al 196, and Yl 181 of Bl) that enhances binding to human Syt II as compared to WT
BoNT/B-Hc. In one embodiment, the mutation comprises one or more mutations that correspond to El 191M/I/T/L/Q (El 191M, El 1911, El 191T, El 191L, or El 191Q), VI 118M, S1199Y/L/F (S1199Y, S 1199L, or S1199F), S1201V, P1117S/M/Y (P1117S, P1117M, or PI 117Y), Yl 183M, Yl 181M, Al 196Y of Bl, or combinations thereof (Fig. 3A, B). Suitably the mutations are selected form the above mutations at positions 1118, 1191 and 1199 or combinations thereof. In particular, mutations selected from one or more of VI 118M, El 191M/Q/I and SI 199Y may be beneficial. More particularly, the mutation that corresponds to position E1191M or E1191Q of Bl is envisioned, since they display the strongest enhancement for binding h-Syt II. The mutations corresponding to El 191M or E1191Q of Bl also significantly enhanced binding of BoNT/B-Hc to human Syt I as compared to WT BoNT/B-Hc (Fig. 4A). In one embodiment, the BoNT/B-Hc has two substitution mutations (see paragraph 0084; meets claims 6-8).
The present invention also includes methods for treating a condition typically treated with a neurotoxin (e.g., skeletal muscle conditions, smooth muscle conditions, glandular conditions, a neuromuscular disorder, an autonomic disorder, pain, or an aesthetic/cosmetic condition). Such conditions are associated with unwanted neuronal activity, as determined by the skilled practitioner. The method comprises the step of administering a therapeutically effective amount of a pharmaceutical composition described herein (e.g., containing a botulinum neurotoxin (BoNT) or a chimeric molecule) to the appropriate location in the mammal to reduce the unwanted neuronal activity, to thereby treat the condition. Administration is by a route that contacts an effective amount of the
composition to neurons exhibiting the unwanted activity (see 00100; meets claim 4).
Specific conditions envisioned for treatment by the methods discussed herein include, without limitation, spasmodic dysphonia, spasmodic torticollis, laryngeal dystonia, oromandibular dysphonia, lingual dystonia, cervical dystonia, focal hand dystonia, blepharospasm, strabismus, hemifacial spasm, eyelid disorder, cerebral palsy, focal spasticity and other voice disorders, spasmodic colitis, neurogenic bladder, anismus, limb spasticity, tics, tremors, bruxism, anal fissure, achalasia, dysphagia and other muscle tone disorders and other disorders characterized by involuntary movements of muscle groups, lacrimation, hyperhidrosis, excessive salivation, excessive gastrointestinal secretions as well as other secretory disorders (see 00101). Autonomic nervous system disorders can also be treated with a modified neurotoxin. For example, glandular malfunctioning is an autonomic nervous system disorder. Glandular malfunctioning includes excessive sweating and excessive salivation. Respiratory malfunctioning is another example of an autonomic nervous system disorder. Respiratory malfunctioning includes chronic obstructive pulmonary disease and asthma. Sanders et al. disclose methods for treating the autonomic nervous system; for example, treating autonomic nervous system disorders such as excessive sweating, excessive salivation, asthma, etc., using naturally existing botulinum toxins. The disclosure of Sander et al. is incorporated in its entirety by reference herein. In one embodiment, substantially similar methods to that of Sanders et al. can be employed, but using a modified neurotoxin, to treat autonomic nervous system disorders such as the ones discussed above (see 00104).
8. Claim(s) 1-9 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Dong et al., US 11,104,891 B2; Filed:12/14/17.
Independent claim 1 is drawn to a method for treating an autonomic disorder in a human patient in need thereof, the method comprising administering to the patient a clostridial neurotoxin comprising an HCC domain from a BoNT/B, BoNT/F, BoNT/D, BoNT/D-C, or BoNT/G; wherein said autonomic disorder is selected from:
a. a smooth muscle disorder selected from:
i. a urinary disorder selected from bladder spasms, detrusor-sphincter dyssynergia (DSD), urinary retention, nocturia, urge incontinence and urinary frequency;
ii. a gastrointestinal disorder selected from sphincter of Oddi dysfunction, esophageal spasms, intestinal spasms, gastroparesis, constipation, occasional diarrhoea, and oropharyngeal dysphasia;
iii. a vascular or cardiovascular disorder; and
iv. a sexual disorder;
b. a hypersecretory disorder selected from gustatory sweating, crocodile tears syndrome, excessive mucus secretion, and bromhidrosis;
c. an inflammatory disorder with an autonomic component;
d. a neuroendocrine disorder; and
e. an autonomic disorder associated with a central neurological disorder having cerebellar/pyramidal features.
Dong et al. disclose methods for treating an autonomic disorder comprising administering a modified clostridial neurotoxin (BoNT/B), comprising one or more substitution mutation(s). Moreover, a chimeric BoNT/BA may be generated by replacing the receptor binding domain of BoNT/A with the modified receptor binding domain of BoNT/B (see column 19, lines 47-57; meeting claim 1-5). Conditions typically treated with a neurotoxin include smooth muscle conditions and autonomic disorders. Specific conditions include cerebral palsy, neurogenic bladder, anal fissure, achalasia, dysphagia, lacrimation, hyperhidrosis, excessive salivation and gastrointestinal secretions as well as other secretory disorders. Respiratory malfunction is another example of an autonomic nervous system as well as respiratory malfunctioning including chronic obstructive pulmonary disease and asthma (see column 38, lines 14-35; meeting claims 1-3; see column 23, lines 1-5).
Dong discloses that “Enhanced binding” when used to describe the binding affinity of a modified BoNT molecule of the present disclosure to a cell, refers to an increase in the binding affinity for a cell (e.g., increased by 50% of the binding affinity of the wild type molecule) see column 11, lines 39-45; meeting claim 6). The modified BoNT polypeptides of the present disclosure may further comprise a series of mutation in BoNT/B receptor binding domain in positions corresponding to 1178, 1191 or 1199 in BoNT/B1, which significantly enhance binding of BoNT/B to human syt II (see column 23, lines 41-60; meetings claims 7-9). A series of mutations in BoNT/B receptor binding domain in positions 1191 and 1199 (e.g., E1191M/S1199Y) (see column 8, lines 66-67; and column 9, line 1; meeting limitation of claim 7-8). Dong et al. disclose that the dosing regimen can vary over time. The particular dosage regimen, i.e., dose, timing and repetition, will depend on particular subject’s medical history, as well as the properties of the polypeptide.
The active method steps of the prior art are identical to those as claimed. The amount of neurotoxin administered is necessarily at a dose that is 1.1 times to 100 times a dose of BoNT/A thereby treating said autonomic disorder, absent evidence to the contrary.
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.
9. Claim(s) 1-18 are rejected under 35 U.S.C. 103 as being unpatentable over Dong et al., US 11,104,891 B2; Filed:12/14/17.
Independent claim 1 is drawn to a method for treating an autonomic disorder in a human patient in need thereof, the method comprising administering to the patient a clostridial neurotoxin comprising an HCC domain from a BoNT/B, BoNT/F, BoNT/D, BoNT/D-C, or BoNT/G; wherein said autonomic disorder is selected from:
a. a smooth muscle disorder selected from:
i. a urinary disorder selected from bladder spasms, detrusor-sphincter dyssynergia (DSD), urinary retention, nocturia, urge incontinence and urinary frequency;
ii. a gastrointestinal disorder selected from sphincter of Oddi dysfunction, esophageal spasms, intestinal spasms, gastroparesis, constipation, occasional diarrhoea, and oropharyngeal dysphasia;
iii. a vascular or cardiovascular disorder; and
iv. a sexual disorder;
b. a hypersecretory disorder selected from gustatory sweating, crocodile tears syndrome, excessive mucus secretion, and bromhidrosis;
c. an inflammatory disorder with an autonomic component;
d. a neuroendocrine disorder; and
e. an autonomic disorder associated with a central neurological disorder having cerebellar/pyramidal features.
Dependent claim 9 is drawn to the method of claim 3, wherein the dose of the clostridial neurotoxin administered is about 1.1 time to about 100 times lower than the dose of BoNT/A required for treating the autonomic disorder.
Dependent claim 10 is drawn to the method of claim 3, wherein the dose of the clostridial neurotoxin ranges from about 0.00025 ng to about 3 ng.
Dong et al. teaches methods for treating an autonomic disorder comprising administering a modified clostridial neurotoxin (BoNT/B), comprising one or more substitution mutation(s). Moreover, a chimeric BoNT/BA may be generated by replacing the receptor binding domain of BoNT/A with the modified receptor binding domain of BoNT/B (see column 19, lines 47-57; meeting claim 1-5). Conditions typically treated with a neurotoxin include smooth muscle conditions and autonomic disorders. Specific conditions include cerebral palsy, neurogenic bladder, anal fissure, achalasia, dysphagia, lacrimation, hyperhidrosis, excessive salivation and gastrointestinal secretions as well as other secretory disorders. Respiratory malfunction is another example of an autonomic nervous system as well as respiratory malfunctioning including chronic obstructive pulmonary disease and asthma (see column 38, lines 14-35; meeting claims 1-3; see column 23, lines 1-5).
Dong teaches that “Enhanced binding” when used to describe the binding affinity of a modified BoNT molecule of the present disclosure to a cell, refers to an increase in the binding affinity for a cell (e.g., increased by 50% of the binding affinity of the wild type molecule) see column 11, lines 39-45; meeting claim 6). The modified BoNT polypeptides of the present disclosure may further comprise a series of mutation in BoNT/B receptor binding domain in positions corresponding to 1178, 1191 or 1199 in BoNT/B1, which significantly enhance binding of BoNT/B to human syt II (see column 23, lines 41-60; meetings claims 7-9). A series of mutations in BoNT/B receptor binding domain in positions 1191 and 1199 (e.g., E1191M/S1199Y) (see column 8, lines 66-67; and column 9, line 1; meeting limitation of claim 7-8). Dong et al. teach that the dosing regimen can vary over time. The particular dosage regimen, i.e., dose, timing and repetition, will depend on particular subject’s medical history, as well as the properties of the polypeptide.
The active method steps of the prior art are identical to those as claimed. The amount of neurotoxin administered is necessarily at a dose that is 1.1 times to 100 times a dose of BoNT/A thereby treating said autonomic disorder, absent evidence to the contrary.
Dong et al. do not specifically teach the specific dose of clostridial neurotoxin as recited in claim 9-11.
It would have been obvious before the effective filing date of the presently claimed invention to optimize the dose of said neurotoxin of Dong et al. with a reasonable expectation of success. The skilled artisan would have been motivated to make this modification because it is the result of routine optimization as suggested by Dong which teaches that the dosage regimen, i.e., dose, timing and repetition, will depend on particular subject’s medical history, as well as the properties of the neurotoxin to be administered.
Regarding the specific concentrations listed in the instant claims, MPEP 2144.05 states, “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955) (Claimed process which was performed at a temperature between 40°C and 80°C and an acid concentration between 25% and 70% was held to be prima facie obvious over a reference process which differed from the claims only in that the reference process was performed at a temperature of 100°C and an acid concentration of 10%.); see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382 ("The normal desire of scientists or artisans to improve upon what is already generally known provides the motivation to determine where in a disclosed set of percentage ranges is the optimum combination of percentages."); In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969) (Claimed elastomeric polyurethanes which fell within the broad scope of the references were held to be unpatentable thereover because, among other reasons, there was no evidence of the criticality of the claimed ranges of molecular weight or molar proportions.). For more recent cases applying this principle, see Merck & Co. Inc. v. Biocraft Laboratories Inc., 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989); In re Kulling, 897 F.2d 1147, 14 USPQ2d 1056 (Fed. Cir. 1990); and In re Geisler, 116 F.3d 1465, 43 USPQ2d 1362 (Fed. Cir. 1997).”
Accordingly, the subject matter of claims 1-18 would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the presently claimed invention, absent evidence to the contrary.
Conclusion
10. No claim is allowed.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAKIA J JACKSON-TONGUE whose telephone number is (571)272-2921. The examiner can normally be reached Monday-Friday 930AM-530PM.
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/LAKIA J JACKSON-TONGUE/Examiner, Art Unit 1645 July 23, 2026
/BRIAN GANGLE/Primary Examiner, Art Unit 1645
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