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 .
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings (Figures 3-4) are not identified by sequence identifiers in accordance with 37 CFR 1.821(d). Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
DETAILED ACTION
Status of Application/Election/Restrictions
Applicant's election with traverse of Group II, SEQ ID NO:4 and Wilson’s disease in the reply filed on September 17, 2025 is acknowledged. The traversal is on the ground(s) that the invention has a special technical feature and possesses unity of invention because Barbas (WO2014039585) or Sidhu (US20120129715) does not teach SEQ ID NO:7 (-HCHVDDHIIGGM-) (corrected sequence for SEQ ID NO:7 based on the sequence listing submitted on 09/17/2025) and the recited sequences share a single general inventive concept because they are derived from ceruloplasmin and the recited disease may be induced by copper metabolic disorders. Applicant’s arguments have been fully considered but they are not persuasive because the limitation “a peptide represented by an amino acid sequence shown in SEQ ID NO:3, 4 or 7” recited in independent claim 15 encompass any fragments within the sequence of SEQ ID NO:3, 4 or 7, which is taught by Kataoka et al.(JP2010183857; published Aug 26, 2010, priority Feb 10, 2009, see the sequence alignment) based on the search using the corrected sequence of SEQ ID NO:7 submitted on 09/17/2025. Therefore, claim 15 is anticipated by Kataoka et al. (JP2010183857). Since the 1st claimed invention has no special technical feature, it cannot share a special technical feature with the other claimed inventions. Thus, Applicant’s inventions do not contribute a special technical feature when view over the prior art, they do not have a single inventive concept and so lack unity of invention. Further, each species of SEQ ID NO: differs with respect to its composition and structures and so are the effects for the reasons set forth in the office action dated 07/22/2025. Furthermore, the etiology and potential molecular mechanisms underlying each species of diseases are very different from each other for the reasons set forth in the prior office action dated 07/22/2025 because the patient populations in different diseases are also different from each other, which requires different diagnoses, equipment, steps and treatments for these different groups of patients. Therefore, these species do not share a common corresponding technical feature; and thus lack unity of invention. Moreover, searching and examining all sequences and diseases are not coextensive and thus would impose serious burden to the Examiner.
Upon reconsideration, the species election between SEQ ID NOs: 4 and 7 is withdrawn because the sequence of SEQ ID NO:7 is a nested sequence of SEQ ID NO:4. The subject matter to the extent of SEQ ID NO:7 is included and under examination in this office action.
The requirement of the rest of restriction is still deemed proper and is therefore made FINAL.
Claims 1-14, 21 and 23-24 are canceled. Claim 22 is amended. Claims 15-20 and 22 are pending in this application. Claims 15-17 are withdrawn with traverse (filed 09/17/2025) from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on September 17, 2025.
Claims 18-20 and 22 are under examination with respect to SEQ ID NOs: 4 and 7 and Wilson’s disease in this office action.
Drawings
The drawings are objected to because no sequence identification has been provided for the nucleic acid sequences presented in Figures 3-4. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Objections
Claims 15-17 are objected to because of the following informalities: the status of the claims 15-17 is incorrect because these claims are withdrawn from consideration. Appropriate correction is required.
See MPEP 714 & 37 CFR 1.121.
“In the claim listing, the status of every claim must be indicated after its claim number by using one of the following identifiers in a parenthetical expression: (Original), (Currently amended), (Canceled), (Withdrawn), (Previously presented), (New), and (Not entered).”
Claim Rejections - 35 USC § 112
8. The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 20 is 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.
Claim 20 recites the limitation "the concentration" in line 2 of the claim. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 112
9. 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 18-20 and 22 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 partially restoring myelination from Copper overexposure-induced myelination damage, increasing reduced GFP expression levels caused by Copper overexposure and decreasing increased heart rates caused by Copper overexposure in an animal model of Copper-induced demyelination, zebrafish transformant (i.e. mGFP transgenic) treated with 4uM Copper, by administering a copper oxidase peptide CP001 (SEQ ID NO:3), CP002 (SEQ ID NO:4) or CP002s (SEQ ID NO:7) to the animal model of copper-induced demyelination (zebrafish transformant treated with 4uM Copper) as compared to the animal model with no treatment, does not reasonably provide enablement for a method for preventing, alleviating or treating all forms of neurological diseases by a composition comprising one or more of the claimed peptides of SEQ ID NOs:3, 4 and/or 7 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 invention of claims 18-20 and 22 that is directed to a method of prevention and curing.
“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 18-20 and 22 are drawn to a method for preventing, alleviating or treating all forms of neurological diseases by administering to a subject in need thereof a composition comprising one or more of peptides selected from the group consisting of SEQ ID NOs:3, 4 and 7.
The claims encompass methods of treating and preventing all forms of neurological diseases caused by any mechanisms using a composition comprising one or more of peptides selected from the group consisting of SEQ ID NOs:3, 4 and 7, including multiple sclerosis (MS), Parkinson’s disease (PD), Alzheimer’s disease (AD), amyotrophic lateral sclerosis (ALS), Mankes disease and Wilson’s disease (elected).
The instant invention is based on findings that treatment with a copper oxidase peptide CP001 (SEQ ID NO:3), CP002 (SEQ ID NO:4) or CP002s (SEQ ID NO:7) at a concentration of 5uM or 10uM in an animal model of copper overexposure-induced demyelination, zebrafish transformant (i.e. mGFP transgenic) resulted in partially recovered myelination from Copper-induced myelination damage, increasing reduction of GFP expression levels caused by Copper overexposure, and decreasing an increased heart rate caused by Copper overexposure in the animal model of copper-induced demyelination, zebrafish transformant (i.e. mGFP transgenic) treated with 4uM Copper, as compared to the animal model with no treatment or treated with a therapeutic agent for Wilson’s disease, DPA (penicillamine/D-Penicillamine) or TETA (trientine/Trientine) (Examples 5-9, Figures 7-11).
Applicant extrapolates the above findings to the claimed method for preventing, alleviating or treating all forms of neurological diseases by administering to a subject in need thereof a composition comprising one or more of peptides selected from the group consisting of SEQ ID NOs:3, 4 and 7.
First, Applicant is not enabled for a method of preventing a person from getting a neurological disease including all forms of neurological diseases including MS, AD, PD, ALS, Menkes disease or Wilson’s disease (elected) caused by all possible mechanisms because any individual has a potential to develop any neurological disease including all forms of neurological diseases including MS, AD, PD, ALS, Menkes disease or Wilson’s disease caused by all possible different mechanisms. Applicant fails to teach how to identify or predict when and which one person would be susceptible to such a disease or developing the disease and predict when the person would need administration of the claimed peptide to prevent the disease from occurring before the disease occurs.
Neither the specification nor the prior art teaches that administration of the claimed peptide can prevent a person from getting any neurological disease including all forms of neurological diseases including MS, AD, PD, ALS, Menkes disease or Wilson’s disease caused by all possible different mechanisms before the disease occurs. The cause of the diseases can be due to a genetic mutation, which is a natural process. The causes of different forms of neurological diseases including MS, AD, PD, ALS, Menkes disease or Wilson’s disease caused by all possible mechanisms are different.
For example, Wilson’s disease is a rare inherited genetic mutation disease caused by a mutation of the APT7B gene, which cannot be prevented (see p. 15 of the factsheet of Wilson disease retrieved from the Cleveland Clinic website). There are many factors involved in molecular mechanisms contributing to the formation of -amyloid deposits and neurofibrillary tangles in patients with AD. They include genetic mutations affecting the processing of APP or other molecules involved in protein processing and targeting in view of Henstridge et al. (see p. 94, Henstridge et al., Nat. Rev. Neurosci. 2019; 20: 94-107), Tayebati (see p. 106, 1st col, 2nd paragraph, Tayebati, Mech. Ageing Dev. 2006. 127: 100-8) and Sarter (see p. 645, abstract, Sarter, Neurosci. and Biobehav. Rev. 2004. 28: 645-650). Moore et al. teach that the pathogenesis of PD can be familial and associated with different gene deficits including a-synuclein, parkin, PINK1, LRRK, NR4A2 etc. (see p. 59-71, Moore et al., Annu. Rev. Neurosci. 2005; 28:57-87), due to oxidative stress resulting production of ROS and mitochondrial dysfunction or could be due impairment of ubiquitin-proteasome system (see p. 72-74, in particular).
If the cause is due to genetic deficits or mutations, it is impossible to prevent a person from getting or developing AD because the gene mutation or gene deficiency is a natural process result. The specification fails to provide sufficient guidance as to enable one of skill in the art to practice the invention as it pertains to a method of prevention. Further, Applicant also fails to provide specific guidance as to what specific amount of the claimed peptide can be used and thus would be effective to prevent all forms of neurological diseases including MS, AD, PD, ALS, Menkes disease or Wilson’s disease caused by all possible mechanisms. Thus, a skilled artisan cannot contemplate a right amount to prevent the disease or to prevent a person from getting the disease.
Second, based on the specification and the prior art, Applicant is enabled for restoring myelination from myelination damage caused by copper overexposure, restoring and increasing GFP expression from decreased GFP expression levels caused by copper overexposure, and restoring and decreasing heart rates from increased heart rates caused by copper overexposure in an animal model of copper overexposure-induced demyelination in zebrafish transformant (i.e. mGFP transgenic) treated with 4uM Copper, by administering to the animal model a copper oxidase peptide CP001 (SEQ ID NO:3), CP002 (SEQ ID NO:4) or CP002s (SEQ ID NO:7) at a concentration of 5uM or 10uM as compared to no treatment.
The claims are not limited to the methods set forth above but also encompass treatment of all forms of neurological diseases caused by all possible mechanisms including MS, PD, AD, ALS, Mankes disease and Wilson’s disease caused by other mechanisms. However, the specification fails to provide sufficient guidance to enable one of skill in the art to practice the full scope of the claimed invention without undue experiments because of the complexity and unpredictability of different neurological diseases, and lack of support and a well-established correlation between the animal model of copper overexposure-induced demyelination in zebrafish transformant treated with 4uM Copper and the pathogeneses or causes of all forms of neurological diseases including MS, AD, PD, Menkes diseases and Wilson’s diseases caused by other mechanisms in vivo in view of Falkenburger et al. (see p. summary Falkenburger et al., J. Neural. Transm, 2006; 70:261-268), Tayebati (see p. 106, 1st col, 2nd paragraph, Tayebati, Mech. Ageing Dev. 2006. 127: 100-8) and Sarter (see p. 645, abstract, Sarter, Neurosci. and Biobehav. Rev. 2004. 28: 645-650).
Each type of animal models of neurological diseases including MS, AD, PD, ALS, Menkes diseases or Wilson’s diseases only reflects part of pathogenesis of the disease as taught by Tayebati (see p. 106, 1st col, 2nd paragraph, Tayebati, Mech. Ageing Dev. 2006. 127: 100-8) and Sarter (see p. 645, abstract, Sarter, Neurosci. and Biobehav. Rev. 2004. 28: 645-650). Applicant obviously intended to treat all forms of neurological diseases including MS, AD, PD, ALS, Menkes diseases or Wilson’s diseases by using the claimed peptide of SEQ ID NO:3, 4 and/or 7. However, the specification fails to provide a well-established correlation among different forms of neurological diseases including MS, AD, PD, ALS, Menkes diseases or Wilson’s diseases caused by different mechanisms. The specification fails to establish that different forms of neurological diseases including MS, AD, PD, ALS, Menkes diseases or Wilson’s diseases caused by different mechanisms can be treated by the same drugs or same conditions or have the same effects in response to the same drugs. Thus, it is unpredictable whether one treatment for one specific disorder can be applied to another disorder, indicating undue experimentation is required by a skilled artisan to perform while practicing the claimed invention.
While the skill level in the art is high, the level of predictability is low. The molecular mechanisms underlying different neurological diseases including MS, AD, PD, ALS, Menkes diseases or Wilson’s diseases are different. For example, cognitive dysfunction or dementia of AD are unclear (see p. 94; Henstridge et al. Nat. Rev. Neurosci. 2019; 20: 94-107). The specification provides insufficient guidance to demonstrate that administration of the claimed peptide of SEQ ID NOs: 3,4 and/or 7 can treat cognitive dysfunction or dementia in AD because myelination damage caused by Copper overexposure is not the only cause of cognitive dysfunction or dementia in AD. Several factors and genes are involved in pathogenesis of AD including ageing, inflammation and immune response, APP, presenilin1/2, ApoE and genes involved in the amyloid cascade, genes involved in the mitochondrial cascade as taught by Swerdlow (p. 348-344, Swerdlow, Clin. Interv. Ageing 2007; 2:347-359), Atwood et al. (p. abstract; Atwood et al., J. Alzheimer’s Disease; 2015; 47:33-47) and Henstridge et al. (p. 95-103; Henstridge et al., Nat. Rev. Neurosci. 2019; 20: 94-107).
It is also known that fully developed animal models for neurodegenerative diseases are still lacking especially for AD because the complexity of the disease and deficiency of characterized cognition (see p. 403, abstract. Anger. Neurotoxicology 1991. 12: 403-13). For example, the animal model of brain amyloidosis induced by acute or infusion of Ab as described in the instant case could only be used to screening for inhibiting the formation of Ab but not for evaluating the generation of Ab by the effects of b-and g-secretase, which is another molecular mechanism for the pathogenesis of AD (see p. 106, 1st col, 2nd paragraph, Tayebati. Mech. Ageing Dev. 2006. 127: 100-8). The art also recognizes that although the Morris water maze behavioral test is a popular choice used in studies determining effects of learning and memory, the test has been disappointing in the predictive validity of data from animal tests on learning and memory used to discover and characterize drugs for the treatment of cognitive impairment and dementia in clinical testing. The animal tasks generate a high rate of false positive (see p. 646, 2nd col. 2nd paragraph) and the validity of the test itself is also a part of the research process (see p. 645, abstract, Sarter. Neurosci. and Biobehav. Rev. 2004. 28: 645-650). Thus, in order to closely reflect the data obtained from animal models to the real situation of Alzheimer’s disease in humans, it has been proposed that a rodent model should include 1) tests currently used to identify in rodents deficits associated with AD; 2) tests to identify Alzheimer-related signs in patients; and 3) tests that relate to theoretical constructs of human and animal cognition, which should include at least spatial learning and memory (such as Morris Water Maze and Radial Arm Maze), delayed recall match-to-sample, serial response learning, and visual discrimination (such as vertical vs. horizontal stimuli).(see p. 403, abstract. Anger. Neurotoxicology 1991. 12: 403-13).
Moore et al. teach that the pathogenesis of PD can be familial and associated with different gene deficits including a-synuclein, parkin, PINK1, LRRK, NR4A2 etc. (see p. 59-71, Moore et al., Annu. Rev. Neurosci. 2005; 28:57-87), due to oxidative stress resulting production of ROS and mitochondrial dysfunction or could be due impairment of ubiquitin-proteasome system (see p. 72-74, in particular). While several models of PD have been created and used for evaluation of drugs on PD or pathogeneses of PD, none of the currently available models of PD completely reflect the PD in humans (see p. 1. Jagmag et al., Front. Neurosci. 2016; 9:503. Doi:10.3389/fnins.2015.00503). Potashkin et al. teach that current animal models do not replicate the true pathophysiology occurring in idiopathic PD and thus the results from animal models often do not translate to the clinic (see p.1, abstract; Potashikin et al., Parkinson’s Disease, 2011; 658083; doi:104061/2011/658083). Thus, it is unpredictable whether the claimed peptide of SEQ ID NO:3, 4 and/or 7 can be used for treating all forms of neurological diseases including MS, AD, PD, ALS, Menkes diseases or Wilson’s diseases caused by different mechanisms or other mechanisms because there is no well-established correlation between the restoring myelination from myelination damage caused by Copper-overexposure, restoring GFP expression from reduced GFP expression caused by Copper-overexposure and restoring heart rates from increased heart rates caused by Copper-overexposure in an animal model of copper overexposure-induced demyelination in zebrafish transformant (i.e. mGFP transgenic) treated with 4uM Copper and the pathogeneses or causes of all forms of neurological diseases including MS, AD, PD, ALS, Menkes diseases or Wilson’s diseases caused by different mechanisms or other mechanism, indicating that undue experimentation is required by a skilled artisan to perform while practicing the full scope of the claimed invention.
In this case, Applicant is enabled for restoring myelination damage caused by copper overexposure, increasing decreased GFP expression levels caused by copper overexposure, and decreasing increased heart rates caused by copper overexposure in an animal model of copper overexposure-induced demyelination in zebrafish transformant (i.e. mGFP transgenic) treated with 4uM Copper, by administering to the animal model a copper oxidase peptide CP001 (SEQ ID NO:3), CP002 (SEQ ID NO:4) or CP002s (SEQ ID NO:7) at a concentration of 5uM or 10uM as compared to no treatment. However, the specification fails to provide sufficient guidance or evidence to demonstrate that all forms of neurological diseases including MS, AD, PD, ALS, Menkes diseases or Wilson’s diseases caused by different mechanisms can be treated or prevented by the claimed peptide of SEQ ID NO:3,4 or 7 because there is no well-established correlation between restoring myelination damage induced by Copper overexposure, increasing decreased GFP expression levels caused by copper overexposure, and decreasing increased heart rates caused by copper overexposure in an animal model of copper overexposure-induced demyelination in zebrafish transformant by the claimed peptide of SEQ ID NO:3, 4 and/or 7 and the pathogeneses or causes of neurological diseases including MS, AD, PD, ALS, Menkes diseases or Wilson’s diseases caused by different mechanisms.
Since the pathogenesis of neurological diseases including MS, AD, PD, ALS, Menkes diseases or Wilson’s diseases caused by different mechanisms is complex and the causes of dementia/cognitive dysfunction in neurological diseases including MS, AD, PD, ALS, Menkes diseases or Wilson’s diseases caused by different mechanisms have not been deciphered and are equally complex, it is unpredictable whether the recovery of myelination from myelination damage caused by copper overexposure, the restoring GFP expression levels from reduced GFP expression levels caused by copper overexposure and the restoring and decreasing heart rates from increased heart rates caused by copper overexposure in the animal model of copper overexposure-induced demyelination in zebrafish transformant by the claimed peptide of SEQ ID NO:3, 4 and/or 7 can be applied to neurological diseases including MS, AD, PD, ALS, Menkes diseases or Wilson’s diseases caused by different mechanisms or whether administration of the claimed peptides can treat all forms of neurological diseases including MS, AD, PD, ALS, Menkes diseases or Wilson’s diseases caused by all possible mechanisms, indicating that undue experimentation is required by a skilled artisan to perform while practicing the full scope of 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 preventing, alleviating or treating a neurological disease including MS, AD, PD, ALS, Menkes diseases or Wilson’s diseases caused by all possible mechanisms using the claimed peptide of SEQ ID NO:3, 4 and/or 7.
Claim Rejections - 35 USC § 112
10. Claims 18-20 and 22 are ejected 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
To provide adequate written description and evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include disclosure of complete or partial structure, physical and/or chemical properties, functional characteristics, structure/function correlation, methods of making the claimed product, or any combination thereof.
Claims 18-20 and 22 as amended encompass using one or more of the claimed peptides of SEQ ID NOs: 3, 4 and/or 7 for preventing, alleviating or treating a genus of neurological disease.
Applicant has not disclosed sufficient species of using the claimed peptides for preventing, alleviating or treating the broad genus of neurological diseases.
The specification only disclosed that treatment with a copper oxidase peptide CP001 (SEQ ID NO:3), CP002 (SEQ ID NO:4) or CP002s (SEQ ID NO:7) at a concentration of 5uM or 10uM in an animal model of copper overexposure-induced demyelination, zebrafish transformant (i.e. mGFP transgenic) resulted in partially recovered myelination from Copper-induced myelination damage, increasing reduction of GFP expression levels caused by Copper overexposure, and decreasing an increased heart rate caused by Copper overexposure in the animal model of copper-induced demyelination, zebrafish transformant (i.e. mGFP transgenic) treated with 4uM Copper, as compared to the animal model with no treatment or treated with a therapeutic agent for Wilson’s disease, DPA (penicillamine/D-Penicillamine) or TETA (trientine/Trientine) (Examples 5-9, Figures 7-11). However, the claims are not limited to the method as set forth above but also encompass preventing, alleviating or treating a genus of neurological diseases.
In making a determination of whether the application complies with the written description requirement of 35 U.S.C. 112, first paragraph, it is necessary to understand what Applicant is in possession of and what Applicant is claiming.
M.P.E.P. § 2163 instructs:
An invention described solely in terms of a method of making and/or its function may lack written descriptive support where there is no described or art-recognized correlation between the disclosed function and the structure(s) responsible for the function. . . .
An applicant may show possession of an invention by disclosure of drawings or structural chemical formulas that are sufficiently detailed to show that applicant was in possession of the claimed invention as a whole. . . .
An applicant may also show that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics which provide evidence that applicant was in possession of the claimed invention, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics.”
This standard has not been met in this case. From the specification, Applicant is in possession of restoring myelination from myelination damage caused by copper overexposure, restoring and increasing GFP expression from decreased GFP expression levels caused by copper overexposure, and restoring and decreasing heart rates from increased heart rates caused by copper overexposure in an animal model of copper overexposure-induced demyelination in zebrafish transformant (i.e. mGFP transgenic) treated with 4uM Copper, by administering to the animal model a copper oxidase peptide CP001 (SEQ ID NO:3), CP002 (SEQ ID NO:4) or CP002s (SEQ ID NO:7) at a concentration of 5uM or 10uM as compared to no treatment. However, Applicant is not in possession of using the claimed peptides of SEQ ID NOs: 3, 4 and/or7 for preventing or treating all forms of neurological diseases because neither the specification nor the prior art provides a well-established correlation between the animal model of copper overexposure-induced demyelination in zebrafish transformant (i.e. mGFP transgenic) treated with 4uM Copper and all forms of neurological diseases including MS, AD, PD, ALS, Menkes diseases or Wilson’s diseases caused by all possible mechanisms or other different mechanisms that are not related to copper-overexposure. Since the common characteristics/features of other neurological diseases caused by all possible mechanisms including MS, AD, PD, ALS, Menkes diseases or Wilson’s diseases caused by other different mechanisms that are not related to copper-overexposure and their effects after being treated with the claimed peptides are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of using the claimed peptide of SEQ ID NOs: 3, 4 and/or 7 for preventing or treating the claimed genus of neurological diseases.
Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant 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.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
As discussed above, the skilled artisan cannot envision the detailed characteristics of encompassed genus of neurological diseases and their structural and functional correlation with the animal model of copper overexposure-induced demyelination in zebrafish transformant treated with 4uM Copper, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence.
Therefore, the claimed method has not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163.
Conclusion
11. NO CLAIM IS ALLOWED.
Sequence alignments
SEQ ID NO:2 1019 GKWLLHCHVDDHIIGGMSAIY 1039
SEQ ID NO:4 (CP002; aa1019-1039) 1 GKWLLHCHVDDHIIGGMSAIY 21
SEQ ID NO:7 (CP002S; aa1024-1035) 1024 -----HCHVDDHIIGGM---- 1035
SEQ ID NO:3 (CP001; aa324-344) 1 GSWLVKCHVHDHYVGGMETLL 21
12. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Jung et al. (WO2024225597, published Oct 31, 2024, priority Apr 27, 2023; post-filing reference) teach an O minor ceruloplasmin multicopper oxidase 1 domain mutant peptide comprising the sequence of SEQ ID NO:4 or 7, which meets the limitation “a peptide represented by an amino acid sequence shown in SEQ ID NO:7”(see the sequence alignment below).
SEQ ID NO:4
BQE33274
(NOTE: this sequence has 2 duplicates in the database searched)
ID BQE33274 standard; peptide; 12 AA.
XX
AC BQE33274;
XX
DT 12-DEC-2024 (first entry)
XX
DE O. minor ceruloplasmin multicopper oxidase 1 domain mutant peptide SEQ:4.
XX
KW CP protein; Ceruloplasmin; alzheimers disease; encephalomyelitis; food;
KW huntingtons chorea; iron metabolism disorder; motor neurone disease;
KW movement disorder; multiple sclerosis; mutein; neurological disease;
KW neuromyelitis optica; neuroprotective; optic neuritis; paresthesia;
KW parkinsons disease; prion infection; prophylactic to disease;
KW protein therapy; therapeutic; wilson disease.
XX
OS Callistoctopus minor.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 2
FT /note= "Wild-type Cys substituted by His"
FT Modified-site 12
FT /note= "C-terminal amide"
XX
CC PN WO2024225597-A1.
XX
CC PD 31-OCT-2024.
XX
CC PF 05-MAR-2024; 2024WO-KR002774.
XX
PR 27-APR-2023; 2023KR-00055716.
XX
CC PA (KOAD ) NAT MARINE BIODIVERSITY INST KOREA.
XX
CC PI Jung SH, Lee JH, Jo SM, Kim HB, An HS;
XX
DR WPI; 2024-B52848/091.
XX
CC PT New peptide comprising specific amino acid sequences used in preparing
CC PT medicine or health functional food composition for preventing, improving
CC PT or treating nervous system disease including multiple sclerosis,
CC PT Parkinsons disease, Alzheimers disease, Menkes disease and/or Wilsons
CC PT disease.
XX
CC PS Claim 1; SEQ ID NO 4; 41pp; Korean.
XX
CC The present invention relates to novel peptides derived from
CC ceruloplasmin shown as SEQ ID NOs: 4-7 (see BQE33274-BQE33277). The
CC invention further discloses: (1) a pharmaceutical composition for
CC preventing or treating a nervous system disease comprising the peptide;
CC (2) a food composition and a health functional food composition for
CC preventing or improving the nervous system disease; (3) a method for
CC preventing or treating a neurological disease; and (4) the use of the
CC peptide in the manufacture of a medicament for preventing or treating the
CC nervous system disease. The peptides of the present invention are useful
CC for preventing or treating nervous system diseases such as multiple
CC sclerosis, neuromyelitis optica, and acute disseminated
CC encephalomyelitis. Parkinson's disease, Alzheimer's disease, amyotrophic
CC lateral sclerosis, Huntington's disease, Menkes disease, Wilson's
CC disease, prion disease, occipital horn syndrome, congenital iron
CC metabolism disorder (Aceruloplasminemia), paresthesia, movement disorder,
CC and optic neuritis. The present sequence represents an Octopus minor
CC ceruloplasmin multicopper oxidase 1 domain peptide mutant (C2H)
CC Om_CP002s1. Note: The present sequence is derived from a parent sequence
CC (see BQE33273).
XX
SQ Sequence 12 AA;
Query Match 47.6%; Score 10; Length 12;
Best Local Similarity 100.0%;
Matches 10; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 8 HVDDHIIGGM 17
||||||||||
Db 3 HVDDHIIGGM 12
SEQ ID NO:7
BQE33277
(NOTE: this sequence has 2 duplicates in the database searched)
ID BQE33277 standard; peptide; 9 AA.
XX
AC BQE33277;
XX
DT 12-DEC-2024 (first entry)
XX
DE O. minor ceruloplasmin multicopper oxidase 1 domain mutant peptide SEQ:7.
XX
KW CP protein; Ceruloplasmin; alzheimers disease; encephalomyelitis; food;
KW huntingtons chorea; iron metabolism disorder; motor neurone disease;
KW movement disorder; multiple sclerosis; mutein; neurological disease;
KW neuromyelitis optica; neuroprotective; optic neuritis; paresthesia;
KW parkinsons disease; prion infection; prophylactic to disease;
KW protein therapy; therapeutic; wilson disease.
XX
OS Callistoctopus minor.
OS Synthetic.
XX
FH Key Location/Qualifiers
FT Misc-difference 2
FT /note= "Wild-type Cys substituted by His"
FT Modified-site 9
FT /note= "C-terminal amide"
XX
CC PN WO2024225597-A1.
XX
CC PD 31-OCT-2024.
XX
CC PF 05-MAR-2024; 2024WO-KR002774.
XX
PR 27-APR-2023; 2023KR-00055716.
XX
CC PA (KOAD ) NAT MARINE BIODIVERSITY INST KOREA.
XX
CC PI Jung SH, Lee JH, Jo SM, Kim HB, An HS;
XX
DR WPI; 2024-B52848/091.
XX
CC PT New peptide comprising specific amino acid sequences used in preparing
CC PT medicine or health functional food composition for preventing, improving
CC PT or treating nervous system disease including multiple sclerosis,
CC PT Parkinsons disease, Alzheimers disease, Menkes disease and/or Wilsons
CC PT disease.
XX
CC PS Claim 1; SEQ ID NO 7; 41pp; Korean.
XX
CC The present invention relates to novel peptides derived from
CC ceruloplasmin shown as SEQ ID NOs: 4-7 (see BQE33274-BQE33277). The
CC invention further discloses: (1) a pharmaceutical composition for
CC preventing or treating a nervous system disease comprising the peptide;
CC (2) a food composition and a health functional food composition for
CC preventing or improving the nervous system disease; (3) a method for
CC preventing or treating a neurological disease; and (4) the use of the
CC peptide in the manufacture of a medicament for preventing or treating the
CC nervous system disease. The peptides of the present invention are useful
CC for preventing or treating nervous system diseases such as multiple
CC sclerosis, neuromyelitis optica, and acute disseminated
CC encephalomyelitis. Parkinson's disease, Alzheimer's disease, amyotrophic
CC lateral sclerosis, Huntington's disease, Menkes disease, Wilson's
CC disease, prion disease, occipital horn syndrome, congenital iron
CC metabolism disorder (Aceruloplasminemia), paresthesia, movement disorder,
CC and optic neuritis. The present sequence represents an Octopus minor
CC ceruloplasmin multicopper oxidase 1 domain peptide mutant
CC (C2H/10_12delGGM) Om_CP002s4. Note: The present sequence is derived from
CC a parent sequence (see BQE33273).
XX
SQ Sequence 9 AA;
Query Match 33.3%; Score 7; Length 9;
Best Local Similarity 100.0%;
Matches 7; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 8 HVDDHII 14
|||||||
Db 3 HVDDHII 9
Kataoka et al. (JP2010183857, published Aug 26, 2010, priority Feb 10, 2009) teach human ceruloplasmin peptide #2 comprising the sequence of -HCHVTDHIHAGM-, which meets the limitation “a peptide represented by an amino acid sequence shown in SEQ ID NO:7”(see the sequence alignment below).
SEQ ID NO:7
AYH38485
ID AYH38485 standard; peptide; 16 AA.
XX
AC AYH38485;
XX
DT 14-OCT-2010 (first entry)
XX
DE Human ceruloplasmin (hCp) peptide #2.
XX
KW biosensor; ceruloplasmin; enzyme electrode; protein detection.
XX
OS Homo sapiens.
XX
CC PN JP2010183857-A.
XX
CC PD 26-AUG-2010.
XX
CC PF 10-FEB-2009; 2009JP-00028988.
XX
PR 10-FEB-2009; 2009JP-00028988.
XX
CC PA (UYKA-) UNIV KANAZAWA.
XX
CC PI Kataoka K, Jp, Sakurai T, Jp, Maeda Y, Jp, Ito T, Jp;
XX
DR WPI; 2010-K58147/59.
XX
CC PT Electrode catalyst used in fuel cell, has multi copper oxidase having
CC PT type I copper, proline residue existing between specific amino acid
CC PT residues, and hydrogen bond between amide proton of residues and sulfur
CC PT atom of cysteine residue.
XX
CC PS Disclosure; Fig 1; 45pp; Japanese.
XX
CC The present invention relates to a novel electrode catalyst which
CC comprises multi copper oxidase. The electrode catalyst comprises multi
CC copper oxidase which contains multiple copper atoms including at least
CC type I copper, proline residue existing between cysteine residue and
CC histidine residue that forms ligand loop among 2 histidine residues, and
CC hydrogen bonds between the amide proton of substituted amino acid
CC residues and sulfur atom of type I copper coordination cysteine residue.
CC The electrode catalyst of the invention is useful in fuel cell as an
CC oxidizing agent and in biosensor for detecting changes in protein and
CC enzyme structure. The present sequence represents a human ceruloplasmin
CC (hCp) peptide which is the main component of an electrode catalyst for
CC use in detecting changes in protein and enzyme structure.
XX
SQ Sequence 16 AA;
Query Match 73.0%; Score 54; Length 16;
Best Local Similarity 75.0%;
Matches 9; Conservative 0; Mismatches 3; Indels 0; Gaps 0;
Qy 1 HCHVDDHIIGGM 12
|||| ||| ||
Db 3 HCHVTDHIHAGM 14
Weimer et al. (EP1598367, published Nov 23, 2005, priority May 18, 2004) teach human ceruloplasmin protein A3 inner subdomain comprising aa 893-1040 of human ceruloplasmin, which comprises “a peptide represented by an amino acid sequence shown in SEQ ID NO:7”(see the sequence alignment below).
SEQ ID NO:7
AEE18673
ID AEE18673 standard; protein; 148 AA.
XX
AC AEE18673;
XX
DT 26-JAN-2006 (first entry)
XX
DE Human ceruloplasmin protein A3 inner subdomain (aa: 893-1040).
XX
KW protein production; protein engineering; gene therapy; blood-clotting;
KW blood clotting disorder; anticoagulant; thrombolytic; hemostatic;
KW hematological disease; factor VIII deficiency; genetic disorder;
KW ceruloplasmin.
XX
OS Homo sapiens.
XX
FH Key Location/Qualifiers
FT Binding-site 83
FT /note= "Metal (T1-Cu61) binding site"
FT Binding-site 129
FT /note= "Metal (T1-Cu61) binding site"
FT Binding-site 134
FT /note= "Metal (T1-Cu61) binding site"
FT Binding-site 139
FT /note= "Metal (T1-Cu61) binding site"
XX
CC PN EP1598367-A1.
XX
CC PD 23-NOV-2005.
XX
CC PF 18-MAY-2004; 2004EP-00011736.
XX
PR 18-MAY-2004; 2004EP-00011736.
XX
CC PA (ZLBB-) ZLB BEHRING GMBH.
XX
CC PI Weimer T, Schulte S, Hofmann K, Hauser H;
XX
DR WPI; 2005-772265/79.
XX
CC PT Producing a modified homolog of human ceruloplasmin for treating or
CC PT preventing hemophilia A comprises adding to a homolog of human
CC PT ceruloplasmin at least one metal binding site that corresponds to a metal
CC PT binding site in human ceruloplasmin.
XX
CC PS Disclosure; Fig 3; 74pp; English.
XX
CC The invention relates to modified nucleic acid sequences coding for
CC coagulation factors, in particular human factor V and human factor VIII
CC and their derivatives. Modified Factor V and factor VIII have enhanced
CC stability and serve as modified homologs of human ceruloplasmin. The
CC invention also relates to a method of producing a modified homolog of
CC human ceruloplasmin. The method involves adding to a homolog of human
CC ceruloplasmin at least one metal binding site that corresponds to a metal
CC binding site or to an incomplete metal binding site in human
CC ceruloplasmin. Modified homologs of human ceruloplasmin, polynucleotides,
CC plasmids or vectors or host cells are useful in the manufacture of a
CC medicament for treating or preventing blood coagulation disorder
CC preferably hemophilia A. The invention also covers a transfer vector for
CC use in gene therapy, which comprises modified DNA sequences of the
CC invention. The present sequence is the human ceruloplasmin protein A3
CC inner subdomain.
XX
SQ Sequence 148 AA;
Query Match 66.7%; Score 82; Length 148;
Best Local Similarity 66.7%;
Matches 14; Conservative 0; Mismatches 7; Indels 0; Gaps 0;
Qy 1 GKWLLHCHVDDHIIGGMSAIY 21
| ||||||| ||| || |
Db 123 GIWLLHCHVTDHIHAGMETTY 143
13. 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 on 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 on 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 an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see https://ppair-my.uspto.gov/pair/PrivatePair. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Chang-Yu Wang
January 13, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675