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
Status of Application/Election/Restrictions
Claims 1-48 are canceled. Claims 49-83 are pending in this application and under examination in this office action.
Specification
The disclosure is objected to because of the following informalities: The use of the term “Syn-One TestTM” (p. 20), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks. Appropriate correction is required.
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 49-71 and 77-83 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 pre-AIA the applicant regards as the invention.
Claims 49-71 and 77-83 are indefinite because:
i. Claim 49 recites the limitation "the level" in line 2 of the claim. There is insufficient antecedent basis for this limitation in the claim.
ii. The term “reducing” in claim 49 is a relative term which renders the claim indefinite. The term “reducing” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what the “reducing” is relative to. Applicant fails to set forth the metes and bounds of what is encompassed within the definition of “reducing”. Since the metes and bounds are unknown, a skilled artisan cannot envision what would be considered as “reducing one more gastrointestinal symptoms” or “reducing the level of a-syn” recited in the claim. Thus the claim is indefinite.
iii. The term “detectable” in claim 61, 62, 71 or 83 is a relative term which renders the claim indefinite. The term “detectable” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what the “detectable level” is relative to. Applicant fails to set forth the metes and bounds of what is encompassed within the definition of “detectable”. Since the metes and bounds are unknown, a skilled artisan cannot envision what would be considered “detectable in cerebrospinal fluid or tissue biopsy” recited in the claim. Thus the claim is indefinite.
iv. Claim 63 recites the limitation "the development" in line 2 of the claim. There is insufficient antecedent basis for this limitation in the claim.
v. The term “slowing” in claim 63, “minimal” in claim 77 or “excessive”, “decreased”, “slowing” or “abnormal” in claim 79 is a relative term which renders the claim indefinite. The term “slowing”, “minimal”, “excessive”, “decreased”, or “abnormal” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. It is unclear what the “slowing”, “minimal”, “excessive”, “decreased”, or “abnormal” is relative to. Applicant fails to set forth the metes and bounds of what is encompassed within the definition of “slowing”, “minimal”, “excessive”, “decreased”, or “abnormal”. Since the metes and bounds are unknown, a skilled artisan cannot envision what would be considered as “a minimal motor symptom”, “slowing the development of one or more motor symptoms” or “excessive daytime sleepiness”, “decreased color vision”, “slowing on quantitative motor testing”, or “abnormal substaintia nigra neuroimaging finding” recited in the claims. Thus the claims are indefinite.
vi. The rest of claims are indefinite as depending from an indefinite claim.
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.
Claims 49-83 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for reducing levels of a-syn oligomers but not monomers in the hippocampus by 27.8%, the striatum by 27.9% and the cortex by 49.8% of Thy1SNCA/15 mice immunized with UB312 (SEQ ID NO:112) compared to control Thy1SNCA/15 mice administered with the adjuvant (AdjuPhos® and CpG1) or reducing levels of a-syn in the colon but not duodenum or levels of GFAP in the colonic myenteric ganglia but not duodenum of Thy1SNCA/15 mice immunized with UB312 (SEQ ID NO:112) compared to control Thy1SNCA/15 mice administered with the adjuvant (AdjuPhos® and CpG1), does not reasonably provide enablement for a method of treating, preventing, reducing or inhibiting one or more gastrointestinal symptoms of a synucleinopathy in a subject with a gynecopathy, a method of preventing, delaying the onset of or slowing the development of one or more motor symptoms of a gynecopathy in a subject or a method of treating a synucleinopathy at the prodromal stage in as subject in need thereof, comprising administering to the subject a composition comprising an effective amount of the claimed peptide immunogen construct as broadly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims. In addition, the specification does not enable the inventions of claims 49-83 that are directed to methods of prevention.
“There are many factors to be considered when determining whether there is sufficient evidence to support a determination that a disclosure does not satisfy the enablement requirement and whether any necessary experimentation is ‘undue’. These factors include, but are not limited to: (A) The breadth of the claims; (B) The nature of the invention; (C) The state of the prior art; (D) The level of one of ordinary skill; (E) The level of predictability in the art; (F) The amount of direction provided by the inventor; (G) The existence of working examples; and (H) The quantity of experimentation needed to make or use the invention based on the content of the disclosure. In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)”. See MPEP § 2164.01.
Claims 49-53 and 56-62 are drawn to a method of treating, preventing, reducing, or inhibiting one or more gastrointestinal symptoms of a synucleinopathy and/or reducing the level of a-synuclein (a-syn) in the gastrointestinal (GI) tract of a subject with a synucleinopathy, the method comprising administering to the subject a composition comprising an effective amount of a peptide immunogen construct comprising:(a) a B cell epitope comprising about 10 to about 25 amino acid residues comprising SEQ ID NO: 15;(b) a T helper epitope selected from SEQ ID NOs: 81, 83 and 84; and (c) a heterologous spacer selected from Lys-Lys-Lys, (a,e-N)Lys, and e-N-Lys-Lys-Lys- Lys (SEQ ID NO: 148), or a combination thereof, wherein the B cell epitope is covalently linked to the T helper epitope through the heterologous spacer, and wherein the subject is a mammal.
Claims 54-55 and 63-83 are drawn to a method of preventing, delaying the onset of or slowing the development of one or more motor symptoms of a synucleinopathy in a subject or a method of treating a synucleinopathy at the prodromal stage in a subject in need thereof, the method comprising administering to the subject a composition comprising an effective amount of the claimed peptide immunogen construct set forth above, and wherein the subject is a mammal.
The instant invention is based on findings that immunization with UB312 (SEQ ID NO:112) in Thy1SNCA/15 mice (i.e. a-syn transgenic mice overexpressing 1-2 copies of the gene encoding human wild type a-syn driven by a mouse Thy1 promote) resulted in i) reducing a-syn oligomers but not monomers in the hippocampus by 27.8%, the striatum by 27.9% and the cortex by 49.8% of UB312-treated Thy1SNCA/15 mice compared to control Thy1SNCA/15 mice administered with the adjuvant (AdjuPhos® and CpG1) (figure 5) or ii) reducing levels of a-syn in the colon but not duodenum or GFAP in the colon myenteric ganglia but not duodenum of UB312-treated Thy1SNCA/15 mice compared to control Thy1SNCA/15 mice administered with the adjuvant (AdjuPhos® and CpG1) or wild type mice (figure 9).
Applicant extrapolates the above findings to the claimed methods of treating, preventing, reducing, or inhibiting one or more gastrointestinal symptoms of a synucleinopathy and/or reducing the level of a-synuclein (a-syn) in the gastrointestinal (GI) tract of a subject with a synucleinopathy or preventing, delaying the onset of or slowing the development of one or more motor symptoms of a synucleinopathy in a subject and a method of treating a synucleinopathy at the prodromal stage in a subject in need thereof by the claimed peptide immunogen construct.
First, Applicant is not enabled for a method of treating or preventing one or more gastrointestinal (GI) symptoms of a synucleinopathy or preventing the onset or development of one or more motor symptoms of a synucleinopathy or treating a synucleinopathy at the prodromal stage using the claimed peptide immunogen construct because GI symptoms of a synucleinopathy are accompanied with the synucleinopathy in a subject with a synucleinopathy at the prodromal stage, and motor symptoms of synucleinopathy develop as the synucleinopathy progresses and are accompanied along with the synucleinopathy in view of Gaenslen et al. (see p. 653, 2nd col.; Mov. Dis. 2011; 26:653-658. DOI:10.1002/mds.23499), Pfeiffer (see p. 2-8; Curr. Treat Options Neurol.2018; 20:54. DOI 10.1007/s11940-018-0539-9), Savica et al. (JAMA Neurol. 2018; 75:503-509. Doi:10.1001/jamaneurol.2017.4243) and Fasano et al. (Lancet Neurol.2015; 14:625-39). Gaenslen et al. teach that prodromal or premotor symptoms occur before the initial clinical diagnosis of Parkinson’s disease (PD), and early symptoms are accompanied or caused by the presence of Lewy pathology at the lower brainstem and spinal cord area, and the olfactory bulb before the substantia nigra (SN) is involved to allow the diagnosis of PD; and wherein the prodromal or premotor symptoms include constipation, and other signs of autonomic dysfunction, hyposmia, pain, REM-sleep-behavior disorder (RBD), neuropsychiatric complaints, anxiety, depression, and minor cognitive deficits (see p. 653, 2nd col.; p. 655-658). Pfeiffer teach that gastrointestinal dysfunction is a prominent nonmotor feature of Parkinson’s
disease and dysfunction can be found along the entire length of the gastrointestinal tract (see abstract). Savica et al. teach that certain nonmotor conditions including constipation, anxiety, and rapid eye movement sleep behavior disorder precede the traditional motor Parkinsons’ disease phenotype by long intervals (see abstract).
Any individual has a potential to develop any form of synucleinopathy. Applicant fails to teach how to identify or predict when and which person among us would be susceptible to such a disease or develop the disease, and predict when the person would need administration of the claimed peptide immunogen construct to prevent the disease from occurring in the subject before the disease occur, or to prevent GI symptoms from occurring in the subject with a synucleinopathy before the GI symptoms occur, or to prevent motor symptoms from occurring in the subject with a synucleinopathy at the prodromal stage before the motor symptoms occur. Neither the specification nor the prior art teaches that administration of the claimed peptide immunogen construct can prevent a person from getting any form of synucleinopathy or to prevent a person from getting GI symptoms in a subject with a synucleinopathy or at the prodromal stage or to prevent a person from getting motor symptoms in a subject with a synucleinopathy at the prodromal stage.
A subject with a synucleinopathy has already had or developed GI symptoms in the GI tract of the subject with a synucleinopathy in view of Gaenslen et al. (see p. 653, 2nd col.; Mov. Dis. 2011; 26:653-658. DOI:10.1002/mds.23499), Savica et al. (JAMA Neurol. 2018; 75:503-509. Doi:10.1001/jamaneurol.2017.4243), Pfeiffer (see p. 2-8; Curr. Treat Options Neurol.2018; 20:54. DOI 10.1007/s11940-018-0539-9) and Fasano et al. (see Lancet Neurol.2015; 14:625-39). Neither the specification nor the prior art provides guidance as to how to prevent GI symptoms of a synucleinopathy in the subject with a synucleinopathy because the GI symptoms have already existed in a subject with a synucleinopathy as evidenced by Gaenslen et al. (see p. 653, 2nd col.), Savica et al. (see abstract) and Pfeiffer (see p. 2-8).
Neither the specification nor the prior art provides guidance as to how to prevent or delay the onset or development of motor symptoms of a synucleinopathy in a subject having a synucleinopathy at the prodromal stage because pathological a-syn propagation has already happened in pools of premotor and motor neurons of the lumbar spinal cord in initial phase, detected in the reticular nuclei of the brainstem in early central phase, and detected in vestibular nuclei, deep cerebellar nuclei and primary motor cortex at the prodromal stage; and the subject with a synucleinopathy at the prodromal stage will progress to the development of motor symptoms of a synucleinopathy in view of Ferreira et al. (see abstract; Brain Commun. 2021. Doi:10.1093/braincomms/fcab104). Neither the specification nor the prior art provides guidance as to whether administration of the claimed peptide immunogen construct can prevent the onset or development of motor symptoms in a subject with a synucleinopathy at the prodromal stage or prevent a person with a synucleinopathy at the prodromal stage from getting or developing motor symptoms of a synucleinopathy.
Neither the specification nor the prior art provides sufficient guidance as to whether administration of the claimed peptide immunogen construct can treat a synucleinopathy at the prodromal stage because based on Applicant’s own admission on p. 25-26 of the instant specification, UB312 does not induce widespread glial cell reaction or T-cell infiltration, and there is no significant difference between UB312-treated Thy1SNCA/15 mice and wild type mice in i) three behavior tests: challenging beam traversal test, wire hanging test or pole test, (p. 25, Figure 3); ii) a-syn immunoreactivity in each region of interest (cortex, striatum, hippocampus, substantia nigra, and cerebellum) or total levels of a-syn detected by Western blot (p. 25, figure 4); iii) immunostaining based on Iba1 (microglial marker) and GFAP (astrocyte marker) (p. 26, figure 7), CD3 T cells (T-cell infiltration marker), ICAM1 (endothelial marker) (p. 26, figure 8).
The specification provides no well-established correlation between treatment of a synucleinopathy at the prodromal stage using the claimed peptide immunogen construct and Thy1SNCA/15 mice immunized with UB312 (SEQ ID NO:112) in reduction of a-syn oligomers but not monomers in the hippocampus by 27.8%, the striatum by 27.9% and the cortex by 49.8% of the UB312-treated Thy1SNCA/15 mice compared to control Thy1SNCA/15 mice administered with the adjuvant (AdjuPhos® and CpG1) shown in figure 5 or in reduction of levels of a-syn in the colon but not duodenum or GFAP in the colon myenteric ganglia but not duodenum of UB312-treated Thy1SNCA/15 mice compared to control Thy1SNCA/15 mice administered with the adjuvant (AdjuPhos® and CpG1) or wild type mice shown in figure 9. Thus, it is unpredictable whether administration of the claimed peptide immunogen construct to a subject with a synucleinopathy can treat or prevent GI symptoms of a synucleinopathy in a subject with a synucleinopathy or at the prodromal stage or prevent or delay the onset or development of motor symptoms of a synucleinopathy in a subject with a synucleinopathy at the prodromal stage, indicating that undue experimentation is required by a skilled artisan to perform while practicing the claimed invention.
Therefore, in view of the breadth of the claims, the lack of guidance in the specification, the limited examples, the unpredictability of inventions, and the current status of the art, undue experimentation would be required by one of skill in the art to perform in order to practice the full scope of the claimed invention as it pertains to a method for treating, preventing one or more GI symptoms of a synucleinopathy in a subject with a synucleinopathy, or preventing, delaying the onset or development of one more motor symptoms of a synucleinopathy in subject with a synucleinopathy at the prodromal stage or treating a synucleinopathy at the prodromal stage in a subject in need thereof by administration to the subject the claimed peptide immunogen construct.
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.
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.
Claims 49-83 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang (US2021/0138049, published May 13, 2021, priority Jun 16, 2017, as in IDS) as evidenced by Gaenslen et al. (Mov. Dis. 2011; 26:653-658. DOI:10.1002/mds.23499), Pfeiffer (Curr. Treat Options Neurol.2018; 20:54. DOI 10.1007/s11940-018-0539-9), Savica et al. (JAMA Neurol. 2018; 75:503-509. Doi:10.1001/jamaneurol.2017.4243) and Fasano et al. (Lancet Neurol.2015; 14:625-39).
Claims 49-53 and 56-62 are drawn to a method of treating, preventing, reducing, or inhibiting one or more gastrointestinal symptoms of a synucleinopathy and/or reducing the level of a-synuclein (a-syn) in the gastrointestinal (GI) tract of a subject with a synucleinopathy, the method comprising administering to the subject a composition comprising an effective amount of a peptide immunogen construct comprising:(a) a B cell epitope comprising about 10 to about 25 amino acid residues comprising SEQ ID NO: 15;(b) a T helper epitope selected from SEQ ID NOs: 81, 83 and 84; and (c) a heterologous spacer selected from Lys-Lys-Lys, (a,e-N)Lys, and e-N-Lys-Lys-Lys- Lys (SEQ ID NO: 148), or a combination thereof, wherein the B cell epitope is covalently linked to the T helper epitope through the heterologous spacer, and wherein the subject is a mammal.
Claims 54-55 and 63-83 are drawn to a method of preventing, delaying the onset of or slowing the development of one or more motor symptoms of a synucleinopathy in a subject or a method of treating a synucleinopathy at the prodromal stage in a subject in need thereof, the method comprising administering to the subject a composition comprising an effective amount of the claimed peptide immunogen construct set forth above, and wherein the subject is a mammal.
Wang (US2021/0138049) teaches a method of treating a synucleinopathy (see para. [0032]-[0033]; [0067]; Examples 15, [0352]-[0371]), or reducing the level of a-synuclein in a subject with a synucleinopathy (see Example 15, para. [0359]-[0367]), the method comprising administering to the subject a composition comprising an effective amount of the claimed peptide immunogen construct including the amino acid sequence of SEQ ID NO:112, which is 100% identical to instant SEQ ID NO:112 (see the sequence alignment below; para. [0070]-[0136]; [0137]-[0165], claims 1-25), and wherein the subject is a mammal as in independent claims or a human as in claims 61-62 (see para. [0148]), which meets the limitations recited in instant claims 49-83. The peptide immunogen construct including the amino acid sequence of SEQ ID NO:112 disclosed by Wang meets the limitations “comprises: (a) a B cell epitope comprising the amino acid sequence of instant SEQ ID NO: 15;(b) a T helper epitope comprising the amino acid sequence of instant SEQ ID NO: 83; and (c) a heterologous spacer of instant SEQ ID NO: 148, and wherein the B cell epitope is covalently linked to the T helper epitope through the heterologous spacer” recited in instant claims 49-52, 61-66, 71-75 and 83 (see the sequence alignment below; para. [0024]-[0033]; [0070]-[0136]).
Wang also teaches a method of treating a synucleinopathy the early stage of a synucleinopathy using the claimed peptide immunogen construct including SEQ ID NO:112 (see the sequence alignment; para. [0299]; [0393]; [0415]-[0420]), which meets the limitations recited in claims 54-55 and 63-83 because the early stage of a synucleinopathy is a synucleinopathy at the prodromal stage as recited in claims 54-55 and 63-83. The patient with a synucleinopathy at the early stage (i.e. at the prodromal stage) does not have a motor symptom of the synucleinopathy or exhibits only a minimal motor symptom of the synucleinopathy including muscle rigidity, bradykinesia, tremor at rest and postural instability recited in claims 55, 68 and 71 or has one or more symptoms of the synucleinopathy at the prodromal stage selected from: hyposmia, REM sleep behavior disorder (RBD), excessive daytime sleepiness, depression, cognitive symptom, autonomic nervous system dysfunction, olfactory loss, decreased color vision, slowing on quantitative motor testing, and abnormal substantia nigra neuroimaging finding as recited in claims 77-80 as evidenced by Gaenslen et al. (see p. 653, 2nd col.), Pfeiffer (see p. 2-8), Savica et al. (see p. 503-509) and Fasano et al. (see p. 625-628; p.630-635).
Wang teaches different forms of synucelinopathy including Parkinson’s disease (PD), Parkinson’s disease dementia (PDD), dementia with Lewy bodies (DLB), multiple system atrophy (MSA), neuroaxonal dystrophy and pure autonomic failure (PAF) recited in claims 56-57, 61-62, 69-71 and 81-83 (see para. [0009]-[0012]). The patients with a synucleinopathy have gastrointestinal (GI) symptoms including drooling, salivation, dysphagia, nausea, vomiting, dyspepsia, constipation, abdominal pain, gastroparesis, and fecal incontinence and the GI symptoms occur in the colon as in claims 58-62 as evidenced by Fasano et al. (see p. 625-635).
Wang teaches that the peptide immunogen construct is in a stabilized immunostimulatory complex with a CpG oligonucleotide (ODN) and the composition comprises a mineral salt of aluminum including aluminum hydroxide or aluminum phosphate as recited in claims 53, 61-62, 67, 71, 76 and 83 (see para. [0027]-[0032]; [0137]-[0158], claims 1-25). Wang teaches 0.5mg-1mg of the a-syn peptide immunogen construct per kg or 20-800 mg/ml (see para. [0148]; [0252]), which is overlapping with the claimed range of 50-400mg of the peptide immunogen construct recited in 61-62, 71 and 83 and also teaches intramuscular administration recited in claims 61-62, 71, 83 (see para. [0146]; [0252];[0353]). Thus, claims 49-83 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wang (US2021/0138049) as evidenced by Gaenslen, Pfeiffer, Savica and Fasano.
SEQ ID NO:112
US-16-623-205-112
(NOTE: this sequence has 1 duplicate in the database searched)
Sequence 112, US/16623205
Publication No. US20210138049A1
GENERAL INFORMATION
APPLICANT: UNITED NEUROSCIENCE
APPLICANT: UNS IP HOLDINGS, LLC
APPLICANT: Wang, Chang Yi
TITLE OF INVENTION: PEPTIDE IMMUNOGENS FROM THE C-TERMINAL END OF ALPHA-SYNUCLEIN
TITLE OF INVENTION: PROTEIN AND FORMULATIONS THEREOF FOR TREATMENT OF
TITLE OF INVENTION: SYNUCLEINOPATHIES
FILE REFERENCE: 1008578.100US9 (UNS1001-US)
CURRENT APPLICATION NUMBER: US/16/623,205
CURRENT FILING DATE: 2019-12-16
PRIOR APPLICATION NUMBER: PCT/US2018/037938
PRIOR FILING DATE: 2018-06-15
PRIOR APPLICATION NUMBER: US 62/521,287
PRIOR FILING DATE: 2017-06-16
NUMBER OF SEQ ID NOS: 153
SEQ ID NO 112
LENGTH: 33
TYPE: PRT
ORGANISM: Homo sapiens
FEATURE:
NAME/KEY: PEPTIDE
LOCATION: (1)..(19)
OTHER INFORMATION: MvF5 Th
FEATURE:
NAME/KEY: SITE
LOCATION: (20)..(20)
OTHER INFORMATION: epsilon-K
FEATURE:
NAME/KEY: PEPTIDE
LOCATION: (20)..(23)
OTHER INFORMATION: epsilon K-KKK as a spacer
FEATURE:
NAME/KEY: PEPTIDE
LOCATION: (24)..(33)
OTHER INFORMATION: alpha-Synuclein 126-135
Query Match 100.0%; Score 165; Length 33;
Best Local Similarity 100.0%;
Matches 33; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ISITEIKGVIVHRIETILFKKKKEMPSEEGYQD 33
|||||||||||||||||||||||||||||||||
Db 1 ISITEIKGVIVHRIETILFKKKKEMPSEEGYQD 33
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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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 61-62, 71 and 83 are rejected under 35 U.S.C. 103 as being unpatentable over Wang (US2021/0138049) in view of Mandler et al. (20150306194, published Oct 29, 2015, priority Jul 13, 2015) and evidentiary references: Gaenslen et al. (Mov. Dis. 2011; 26:653-658. DOI:10.1002/mds.23499), Pfeiffer (Curr. Treat Options Neurol.2018; 20:54. DOI 10.1007/s11940-018-0539-9), Savica et al. (JAMA Neurol. 2018; 75:503-509. Doi:10.1001/jamaneurol.2017.4243) and Fasano et al. (Lancet Neurol.2015; 14:625-39).
Wang is set forth above but does not teach that the effective amount is exactly identical to the claimed rang of 50-400 mg recited in claims 61-62, 71 or 83.
Mandler et al. (US2015/0306194) teach a method of treating a synucleinopathy, comprising administering to a subject in need thereof a composition comprising at least one mimotope of an epitope of a-syn that is couped to or fused to a pharmaceutically acceptable carrier protein selected from a non-toxic diphtheria toxin mutant , keyhole limpet hemocyanin (KLH), diphtheria toxin (DT), tetanus toxid (TT) and Haemophilius influenza protein D (protein D) ([0031]-[0035]) or CpG ([0046]-[0055] in an amount of 0.1ng-10mg, 0.5-500mg or 1-100mg per immunization or 0.1ng-10mg, 10ng-1mg or 100ng-300mg/kg body weight (see abstract; para. [0036]; [0038]).
A person of ordinary skill in the art would have recognized that selecting and applying the known amount of the peptide immunogen including 0.5-500mg or 1-100mg per immunization and the known technique disclosed by Mandler to the Wang’s method would have yielded the predictable result of treating a synucleinopathy or a synucleinopathy at prodromal stage, and resulted in an improved method.
The claimed method requires a dose range of 50-400 mg, which overlaps with the range of Wang or Mandler because Wang teach 0.5mg-1mg of the a-syn peptide immunogen construct per kg or 20-800 mg/ml or Mandler teaches 0.1ng-10mg, 0.5-500mg or 1-100mg per immunization or 0.1ng-10mg, 10ng-1mg or 100ng-300mg/kg body weight. Because the claimed range overlaps with the range disclosed by the prior art, a prima facie case of obviousness exists. Note that
In the case where the claimed ranges “overlap or lie inside ranges disclosed by the prior art” a prima faciecase of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990), See MPEP §2144.05-I.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to select and apply the known the known amount of the peptide immunogen including 0.5-500mg or 1-100mg per immunization and the known technique disclosed by Mandler to the Wang’s method, and yield the predictable result of treating a synucleinopathy or a synucleinopathy at prodromal stage.
Further, routine optimization of Wang’s or Mandler’s amount range would have led to the claimed range of 50-400 mg because Wang teach that immunization with a dose range of 0.5mg-1mg of the a-syn peptide immunogen construct per kg or 20-800 mg/ml or Mandler teaches immunization with a dose range of 0.1ng-10mg, 0.5-500mg or 1-100mg per immunization or 0.1ng-10mg, 10ng-1mg or 100ng-300mg/kg body weight achieves induction of anti-a-syn and reducing a-syn aggregation desired in the claimed method. The person of ordinary skill in the art would have found it obvious to optimize within the range taught by Mandler or Wang because Mandler or Wang teaches that this entire range induces production of anti-a-syn and reduces a-syn aggregation, and also teaches how to optimize the dose range of the a-syn peptide immunogen. Note that
“[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.” See In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)”; “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.” see also Peterson, 315 F.3d at 1330, 65 USPQ2d at 1382; In re Hoeschele, 406 F.2d 1403, 160 USPQ 809 (CCPA 1969); 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). See MPEP § 2144.05.
Conclusion
NO CLAIM IS ALLOWED.
Sequence alignment
SEQ ID NO:112 1 ISITEIKGVIVHRIETILFKKKKEMPSEEGYQD 33
SEQ ID NO:15 1 -----------------------EMPSEEGYQD 10
SEQ ID NO:83 1 ISITEIKGVIVHRIETILF-------------- 19
SEQ ID NO:81 1 ISIXEIXXVIVXXIETILF-------------- 19
SEQ ID NO:148 1 -------------------KKKK---------- 4
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Wang (WO2018232369) teaches a method of treating synucleinopathy including Parkinsons disease (PD), multiple systems atrophy (MSA) or dementia with lewy bodies (DLB) in a subject in need thereof, comprising administering to the subject, an immunogen construct comprising a B cell epitope peptide of the alpha-Syn, a T-helper epitope peptide, and an optional heterologous spacer, wherein the immunogen construct includes instant SEQ ID NO:112 (see the sequence alignment below).
SEQ ID NO:112
BFX45671
(NOTE: this sequence has 2 duplicates in the database searched)
ID BFX45671 standard; peptide; 33 AA.
XX
AC BFX45671;
XX
DT 07-FEB-2019 (first entry)
XX
DE UBITh1-spacer-alpha-Synuclein 126-135 fusion construct, SEQ:112.
XX
KW F protein; SNCA protein; Synuclein alpha; alpha-Syn aggregation;
KW alpha-Syn protein; antibody production; antiparkinsonian; b-lymphocyte;
KW fusion protein; immune stimulation; immunoassay; immunoconjugate;
KW lewy body dementia; multiple system atrophy; neurodegenerative disease;
KW neuroprotective; nootropic; parkinsons disease; prophylactic to disease;
KW t-lymphocyte; therapeutic.
XX
OS Homo sapiens.
OS Measles morbillivirus.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Region 1..19
FT /note= "MvF5 Th"
FT Region 20..23
FT /note= "spacer"
FT Misc-difference 20
FT /note= "epsilon-K"
FT Region 24..33
FT /note= "alpha-Synuclein 126-135"
XX
CC PN WO2018232369-A1.
XX
CC PD 20-DEC-2018.
XX
CC PF 15-JUN-2018; 2018WO-US037938.
XX
PR 16-JUN-2017; 2017US-0521287P.
XX
CC PA (UNNE-) UNITED NEUROSCIENCE.
CC PA (UBIU-) UBI US HOLDINGS LLC.
XX
CC PI Wang CY;
XX
DR WPI; 2018-A27628/03.
DR REFSEQ; NP_000336.
XX
CC PT New alpha-synuclein peptide immunogen construct comprising a B cell
CC PT epitope and a T helper epitope, useful for producing antibodies that
CC PT recognize alpha-synuclein and for treating and/or preventing
CC PT synucleinopathies.
XX
CC PS Claim 8; SEQ ID NO 112; 154pp; English.
XX
CC The present invention relates to a novel alpha-synuclein (alpha-Syn)
CC peptide immunogen construct useful for inducing immune response, and
CC treating and/or preventing synucleinopathy in a subject. Synucleinopathy
CC can be Parkinsons disease (PD), multiple systems atrophy (MSA) or
CC dementia with lewy bodies (DLB). The immunogen construct comprises a B
CC cell epitope peptide of the alpha-Syn, a T-helper epitope peptide, and an
CC optional heterologous spacer. The invention further discloses: (1) a
CC composition/pharmaceutical composition comprising one or more alpha-Syn
CC peptide immunogen construct; (2) an isolated antibody or an epitope-
CC binding fragment that specifically binds to the B cell epitope of the
CC alpha-Syn peptide immunogen construct; (3) a composition comprising the
CC isolated antibody or the epitope-binding fragment; (4) a method for
CC producing antibodies that recognize the alpha-Syn in a host; (5) a method
CC for inhibiting the alpha-Syn aggregation in an animal; (6) a method for
CC reducing the amount of the alpha-Syn aggregated in an animal; (7) a
CC method for identifying alpha-Syn aggregates of different sizes in a
CC biological sample using the antibody or the epitope-binding fragment. The
CC present sequence is an UBITh1-spacer-alpha-Synuclein 126-135 immunogen
CC fusion construct comprising a Measles virus fusion protein Th epitope MvF
CC 5 Th (UBITh1), a spacer peptide, and a human alpha-Synuclein B-cell
CC epitope peptide, which is useful in preparing a composition for inducing
CC immune response and treating synucleinopathy in a subject.
XX
SQ Sequence 33 AA;
Query Match 100.0%; Score 165; Length 33;
Best Local Similarity 100.0%;
Matches 33; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 ISITEIKGVIVHRIETILFKKKKEMPSEEGYQD 33
|||||||||||||||||||||||||||||||||
Db 1 ISITEIKGVIVHRIETILFKKKKEMPSEEGYQD 33
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Chang-Yu Wang
July 23, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675
Prosecution Insights