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
Applicant's election with traverse of Group I (claims 1-2 and 4-6) and Parkinson’s disease in the reply filed on November 24, 2025 is acknowledged. The traversal is on the ground(s) that amended claim 1 and dependent claims thereof satisfy unity of invention because the peptide disclosed in WO2006020581, US20050203010 or US2018/0134775 is different the peptide recited in amended claim 1, wherein X1 is F or W and X2 is Y, F or W in SEQ ID NO:5 or X1 is Y and X2 is F or W. Applicant's arguments have been fully considered but they are not found persuasive. The claimed peptide recited amended claims does not have a special technical feature over Ahlijanian et al. (US11142570) or Schenk et al. (US8092801) in view of Kaylor et al. (J. Mol. Biol., 2005; 353:357-372) for the reasons set forth below under the 103 rejections. Therefore, claim 1 does not recite a special technical feature, defined by the PCT rules as a feature that defines a contribution over the prior art. 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 have a single inventive concept and so lack unity of invention. In addition, an application may properly be required to be restricted to one of two or more claimed inventions if they are able to support separate and different patents. See MPEP § 806.04 - § 806.04 (j). The search and examination of the plural inventions would impose a serious burden upon the Examiner.
The requirement for the restriction is still deemed proper and is therefore made FINAL.
Claims 1 and 4-7 are amended. Claims 1-7 are pending in this application. Claims 3 and 7 are withdrawn with traverse (filed 11/24/2025) from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on November 24, 2025.
Claims 1-2 and 4-6 are under examination in this office action.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Specification
The disclosure is objected to because of the following informalities: The recitation “a peptide of a synthesized α-synuclein C-terminal 20 residues…. (SEQ ID NO: 6) or 10 residues EGYQDYEPEA (1 μM) (SEQ ID NO: 6)” on p.16 of the specification filed 09/08/2025 is objected to because the same SEQ ID NO: is recited for different peptides with different residues. Appropriate correction is required.
Claim Objections
Claims 3 and 7 are objected to because of the following informalities: the status of claims 3 and 7 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 1-2 is objected to because of the following informalities: the recitation “being 30 or less” recited in claim 1 is unclear. Appropriate correction is required.
The recitation “FABP3” recited in claim 2 is not a unique or common abbreviation in the art. Applicants are required to spell out “FABP3” at the first usage. 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 1-2 and 4-6 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 1-2 and 4-6 are indefinite because:
i. Regarding claim 1, the limitations “a peptide represented by…” and “an amino acid represented by…” recited in claim 1 is indefinite because it is unclear what other peptides and sequences are included and within the scope of the claim. Applicant fails to set forth the metes and bounds of what is encompassed within the limitations “a peptide represented by…” and “an amino acid sequence represented by…”. Since the metes and bounds are unknown, a skilled artisan cannot envision what other peptides and/or sequences are included and within the scope of the claim. In addition, there is insufficient antecedent basis for the limitation “the length of said peptide being 30 or less” in the claim and it is unclear what the limitation “the length…being 30 or less” means. Thus, the claim is indefinite. For searching and examination purposes, the limitation “a peptide represented by (i) or (ii) below: (i) a peptide consisting of an amino acid represented by EEG(X1)QD(X2)EPEA (SEQ ID NO:5), wherein X1 is F or W and X2 is Y, F or W, or X1 is Y and X2 is F or W…or (ii) a peptide comprising…” recited in claim 1 is interpreted as “a peptide has a structure of (i) or (ii) below: (i) a peptide consisting of EEG(X1)QD(X2)EPEA (SEQ ID NO:5), wherein X1 is F or W and X2 is Y, F or W; or X1 is Y and X2 is F or W; or (ii) a peptide comprising EEG(X1)QD(X2)EPEA (SEQ ID NO:5) and having less than 30 amino acid residues in length”.
ii. Regarding claim 2, the limitation “16th phenylalanine in an amino acid sequence of native FABP3 protein” is indefinite because it is unclear what sequence and what native FABP3 protein is. Based on the NCBI protein database, there are multiple forms of FABP3 proteins in different lengths. It is unclear which sequence the limitation “16th phenylalanine” is based on, and whether the limitation “16th phenylalanine’ is the same position across all sequences and forms of native FABP3 protein. Thus, the claim is indefinite.
iii. The rest of claims are indefinite as depending from an indefinite 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 4-6 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 blocking interaction of FABP3 with a-synuclein or the uptake of the ATTO-550-labeled wild type α-synuclein monomer into the cultured dopamine neurons by the claimed peptide having the structure of EEG(X1)QD(X2)EPEA (SEQ ID NO:5) and specific amino acids Y, F, W for X1 and X2 of SEQ ID NO:5 in vitro or in vivo, does not reasonably provide enablement for a method for prevention or treatment of all forms of synucleinopathy by the claimed peptide 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.
“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 4-6 are drawn to a method for prevention or treatment of synucleinopathy, comprising administering to a subject in need thereof the claimed peptide of claim 1 as an active ingredient, wherein the peptide has the structure of EEG(X1)QD(X2)EPEA (SEQ ID NO:5) and specific amino acids Y, F, W for X1 and X2 of SEQ ID NO:5 recited in claim 1. The claims encompass the claimed peptide and its use in a method for treating and preventing all forms of synucleopathy caused by all possible mechanisms including Parkinson’s disease (PD), Lewy body disease (LBD) and multiple system atrophy (MSA).
The instant invention is based on findings that:
i. a-synuclein full length and a-SynP130-140 (SEQ ID NO:4) bound to FABP3 based on (Example 1, Figures 3A-D);
ii. a-SynP130-140 mutants with Y133F, Y136F, Y133W, Y133F/Y136F, F133F/Y136W and Y136W/Y136W bound to FABP3. The binding of Y133F to FABP3 is 2-fold stronger binding affinity than the nature sequence and the additional mutation at Y136 failed to further strength the binding affinity (Example 2, figures 4A-F).
iii. Adding equimolar FABP3 to α-synuclein completely suppressed the aggregation of a-synuclein. When equimolar FABP3 and a-SynP130-140 or a-SynP130-140-Y133F mutant were added simultaneously to α-synuclein, the peptide binds to FABP3 before α-synuclein (Examples 3, Figures 5A-B). The a-SynP130-140-Y133F peptide preferentially binds to FABP3 in a dose-dependent manner, and α-synuclein failing to bind to FABP3 (Example 4, Figures 6A-B). Adding the a-SynP130-140-Y133F peptide to the a-Syn-FABP3 complex releases a-Syn from FABP3, and a-Syn released from FABP3 forms amyloid fibril aggregates (Example 5, Figures 7A).
iv. The cultured dopaminergic neurons took up uptake the ATTO-550-labeled wild type α-synuclein monomer into the cells, but not the ATTO-550-labeled α-synuclein with a C-terminal amino acids 130-140 deletion compared to controls (Example 7, FIG. 9A-9B). The uptake of the ATTO-550-labeled wild type α-synuclein monomer into the cultured dopamine neurons is inhibited a peptide of the C-terminal 20 amino acid residues of a-synuclein: -DNEAYEMPSEEGYQDYEPEA (SEQ ID NO: 6) or 10 residues EGYQDYEPEA (SEQ ID NO:7) (Example 6, FIG 8A-C).
v. The binding between FABP3 and peptides is based on the interaction of the phenyl group of the 16th phenylalanine in the amino acid sequence of the FABP3 protein with the phenyl group, tyrosine, or tryptophan at position 133 and/or the phenyl group, tyrosine, or tryptophan at position 136 of α-synuclein (Figure 8, Figure 10).
Applicant extrapolates the above findings to the claimed method for treating and preventing all forms of synucleopathy including Parkinson’s disease (PD), Lewy body disease (LBD) and multiple system atrophy (MSA) caused by all possible mechanisms using the claimed peptide.
First, Applicant is not enabled for a method of preventing synucleopathy caused by all possible mechanisms including Parkinson’s disease (PD), Lewy body disease (LBD) and multiple system atrophy (MSA) by the claimed peptide. Neither the specification nor the prior art provides guidance as to how to prevent a person from having synucleopathy including PD, LBD and MSA caused by all possible mechanisms.
Any individual has a potential to develop any form of synucleopathy including PD, LBD and MSA caused by all possible mechanisms. Applicant fails to teach how to identify or predict when and which 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 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 form of synucleopathy including PD, LBD and MSA caused by all possible mechanisms. The cause of the disease can be due to a genetic mutation, which is a natural process. The causes of different forms of synucleopathy including PD, LBD and MSA caused by all possible mechanisms are different. For example, 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 PD 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 synucleopathy including PD, LBD and MSA 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 inhibiting binding between FABP3 and α-synuclein in vitro or the uptake of the ATTO-550-labeled wild type α-synuclein monomer into the cultured dopamine neurons in vitro by the claimed a-SynP130-140 mutant peptide having the structure of EEG(X1)QD(X2)EPEA (SEQ ID NO:5) and specific amino acids Y, F, W for X1 and X2 of SEQ ID NO:5 recited in claim 1. Applicant may be predictably enabled for inhibiting binding between FABP3 and α-synuclein or the uptake of the ATTO-550-labeled wild type α-synuclein monomer into dopamine neurons in vivo.
However, the claims are not limited to the methods set forth above but also encompass treatment of all forms of synucleopathy caused by any possible mechanisms. The specification fails to provide sufficient guidance to enable one of skill in the art to practice the claimed invention without undue experiments because of the complexity and unpredictability of the diseases and failure to provide support a correlation between the in-vitro binding assay or the uptake of the ATTO-550-labeled wild type α-synuclein monomer into cultured dopamine neurons and the treatment of all forms of synucleopathy in vivo in view of Falkenburger et al. (see p. 261, 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 synucleopathy 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 synucleopathy by using the claimed peptide. However, the specification fails to provide a well-established correlation between inhibiting binding of FABP3 to a-synuclein or uptake of a-synuclein in vitro by the claimed peptide and treatment of all forms of synucleopathy caused by different mechanisms by the claimed peptide.
The specification fails to establish that different forms of synucleopathy 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 while practice the claimed invention.
While the skill level in the art is high, the level of predictability is low. The molecular mechanisms underlying cognitive dysfunction or dementia of AD, PD or LBD 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 can treat cognitive dysfunction or dementia in synucleopathy because binding between FABP3 and a-synuclein is not the only cause of cognitive dysfunction or dementia in synucleopathy including PD, LBD and MSA.
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). In addition, 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). For example, while toxin model induced by 6-OHDA, can reproduce behavioral deficits of PD, the effect of 6-OHDA does not mimic the progressive loss seen in PD (see p. 3, in particular). Jagmag et al. teach a combination of toxin-based animal models with genetic models can provide a better tool to evaluate all the symptoms of PD (see p. 7). In this case, while the specification disclosed inhibiting the interaction between FABP3 and a-synuclein in vitro by the claimed a-SynP130-140 mutants, the in vitro assays and in cultures require additional animal models or other different models to verify the effects as taught by Falkenburger et al. (see p. 261, summary Falkenburger et al., J. Neural. Transm, 2006; 70:261-268). In addition, the presence of Lewy bodies (LB) in neurons is the hallmark of PD, the specification fails to teach the relationship between LB in PD or LBD and the blocking the interaction between FABP3 and a-synuclein in vitro by the claimed a-SynP130-140 mutants. Thus, it is unpredictable whether the claimed peptide can be used for treating all forms of synucleopathy including PD, LBD and MSA caused by different mechanisms. The specification fails to provide sufficient guidance or evidence to demonstrate that all forms of synucleopathy including PD, LBD and MSA caused by different mechanisms can be treated or prevented by the claimed peptide because there is no well-established correlation between inhibiting the interaction between FABP3 and a-synuclein uptake of a-synuclein by cultured dopaminergic neurons in vitro by the claimed a-SynP130-140 mutants and the pathogeneses or causes of all forms of synucleopathy including PD, LBD and MSA caused by different mechanisms.
In addition, Falkenburger et al. teaches that the results derived from cellular models induced by 6-OHDA or NMDA in neuronal cultures require additional animal models or other different models to verify the effects (see p.261, summary Falkenburger et al., J. Neural. Transm, 2006; 70:261-268). Since the pathogenesis of all forms of synucleopathy including PD, LBD and MSA caused by different mechanisms is complex and the causes of all forms of synucleopathy including PD, LBD and MSA caused by different mechanisms have not been fully understood and are equally complex, it is unpredictable whether the inhibiting the interaction between FABP3 and a-synuclein or uptake of a-synuclein by cultured dopaminergic neurons in vitro by the claimed a-SynP130-140 mutants can be applied to all forms of synucleopathy including PD, LBD and MSA caused by different mechanisms in vivo, or whether administration of the claimed peptide can treat all forms of synucleopathy including PD, LBD and MSA caused by different mechanisms, 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, no working 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 or preventing synucleopathy including PD, Lewy body disease and multiple system atrophy caused by all possible mechanisms including different mechanisms by the claimed peptide.
10. 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 § 103
11. 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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-2 are rejected under 35 U.S.C. 103 as being unpatentable over Ahlijanian et al. (US Patent No. 11142570, issued on Oct 12,2021, priority Feb 14, 2017) in view of Kaylor et al. (J. Mol. Biol., 2005; 353:357-372).
Ahlijanian et al. (US11142570) teaches an a-synuclein 130-140 peptide (a-SynP130-140: 11aa in length) comprising -EEGYQDYEPEA- (SEQ ID NO:155), which has the structure of EEG(X1)QD(X2)EPEA (SEQ ID NO:5), wherein X1 is Y and X2 is Y (see the sequence alignment below; col.79, Table 1, aa 130-140 of a-syn: SEQ ID NO:155). Ahlijanian teaches the use of the a-SynP130-140 peptide for generation of anti-a-synuclein and for treatment of synucleinopathy including PD, LBD and MSA, which is related to claims 1-2 (see col. 1, lines 43-55; col.13, lines 42-67; col.13, lines 43-67).
But Ahlijanian does not teach that Y2 is F or W; or X1 is F or W and X2 is Y, F or W.
Kaylor et al. teaches that a-synuclein with a mutation of Y133F and/or Y136F does not change the binding or activity of a-synuclein and provides better energy transfer for study a-synuclein aggregation and fibrillation (see p. 356, Abstract; p. 357-360; p. 363-369). Kaylor teaches that a-synuclein lacks Trp residues and an internal probe in a-synuclein with a naturally fluorescent Trp residue is required for studying b-strand conformation of a fibril of a-synuclein. By introduction of tryptophan (W) and phenylalanine (F) to tyrosine residues at positions 39, 125, 133, and 136 in wild-type human a-synuclein can be used for study of the fibrillation properties of a-synuclein. (see p.358; p. 363-369). Kaylor teaches the C-terminal region of a-synuclein mutants with Y133F and/or Y136F, Y133W and/or Y136W are solvent-exposed during fibrillation (p. 369).
A person of ordinary skill in the art would have recognized that selecting and applying the known mutations Y133F and/or Y136F, Y133W and/or Y136W within the C-terminal region of a-synuclein and the known technique disclosed by Kaylor to the Ahlijanian’s a-synuclein 130-140 peptide would have yielded the predictable result of the claimed peptide having the structure of EEG(X1)QD(X2)EPEA (SEQ ID NO:5) wherein X1 is Y and Y2 is F or W; or X1 is F or W and X2 is Y, F or W, and resulted in an improved product.
Using and including the known mutations Y133F and/or Y136F, Y133W and/or Y136W within the C-terminal region of a-synuclein in the Ahlijanian’s a-synuclein 130-140 peptide would generate the claimed peptide with similar properties as those in the Ahlijanian’ a-synuclein 130-140 peptide in binding FAB3 protein as in claim 2 and for pharmaceutical purposes including generation of antibodies against a-synuclein, and expand application of the Ahlijanian’s a-synuclein 130-140 peptide in pharmaceutical purposes or treating diseases mediated a-synuclein, synucleinopathy including PD, LBD and MSA.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the known mutations Y133F and/or Y136F, Y133W and/or Y136W within the C-terminal region of a-synuclein and the known technique disclosed by Kaylor to the Ahlijanian’s a-synuclein 130-140 peptide and yield the predictable result of the claimed peptide having the structure of EEG(X1)QD(X2)EPEA (SEQ ID NO:5) wherein X1 is Y and Y2 is F or W; or X1 is F or W and X2 is Y, F or W for pharmaceutical purposes or treating diseases mediated a-synuclein, synucleinopathy including PD, LBD and MSA.
The sequence search results disclose as follows:
SEQ ID NO:5-X1Y-X2F
Sequence 155, US/16486238
Patent No. 11142570
GENERAL INFORMATION
APPLICANT: BRISTOL-MYERS SQUIBB COMPANY
TITLE OF INVENTION: ANTIBODIES TO ALPHA-SYNUCLEIN AND USES THEREOF
FILE REFERENCE: MXI-554US
CURRENT APPLICATION NUMBER: US/16/486,238
CURRENT FILING DATE: 2019-08-15
PRIOR APPLICATION NUMBER: PCT/US2018/000032
PRIOR FILING DATE: 2018-02-16
PRIOR APPLICATION NUMBER: US 62/460,416
PRIOR FILING DATE: 2017-02-17
NUMBER OF SEQ ID NOS: 182
SEQ ID NO 155
LENGTH: 11
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic: alpha-Syn 130-140
Query Match 95.1%; Score 58; Length 11;
Best Local Similarity 90.9%;
Matches 10; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EEGYQDFEPEA 11
||||||:||||
Db 1 EEGYQDYEPEA 11
SEQ ID NO:5-X1Y-X2W
Sequence 155, US/16486238
Patent No. 11142570
GENERAL INFORMATION
APPLICANT: BRISTOL-MYERS SQUIBB COMPANY
TITLE OF INVENTION: ANTIBODIES TO ALPHA-SYNUCLEIN AND USES THEREOF
FILE REFERENCE: MXI-554US
CURRENT APPLICATION NUMBER: US/16/486,238
CURRENT FILING DATE: 2019-08-15
PRIOR APPLICATION NUMBER: PCT/US2018/000032
PRIOR FILING DATE: 2018-02-16
PRIOR APPLICATION NUMBER: US 62/460,416
PRIOR FILING DATE: 2017-02-17
NUMBER OF SEQ ID NOS: 182
SEQ ID NO 155
LENGTH: 11
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic: alpha-Syn 130-140
Query Match 86.4%; Score 57; Length 11;
Best Local Similarity 90.9%;
Matches 10; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EEGYQDWEPEA 11
||||||:||||
Db 1 EEGYQDYEPEA 11
12. Claims 1-2 and 4-6 are rejected under 35 U.S.C. 103 as being unpatentable over Ahlijanian et al. (US11142570) in view of Kaylor et al. (2005) as applied to claims 1-2 above, and further in view of Schenk et al. (US8092801, issued Jan 10, 2012, priority Feb 23, 2007).
Ahlijanian and Kaylor are set forth above but fail to teach that the claimed peptide is less than 30 amino acid residues recited in claim 1 and its use for active immunization in the method of treatment of synucleopathy including PD, LBD and MSA recited in claims 4-6.
Schenk et al. (US8092801) teaches an a-SynP130-140 peptide comprising the amino acid sequence of SEQ ID NO:41 (13 aa in length), which has the structure of EEG(X1)QD(X2)EPEA (SEQ ID NO:5), wherein X1 is Y and X2 is Y (see the sequence alignment below; col.7, lines 10-24;) and no more 30 amino acid residues in length (see col.7 lines 37-60) and its for treating synucleopathy including PD, LBD and MSA by active immunization of the to a subject in need thereof (see col.6, 45-54; col. 6, line 61-col.7, line 61).
A person of ordinary skill in the art would have recognized that selecting and applying the known a-SynP130-140 peptide or the known a-SynP130-140 peptide being less than 30 amino acids in length and the known method of active immunization and the known technique disclosed by Schenk to the method and a-SynP130-140 peptide mutants of Ahlijanian and Kaylor would have yielded the predictable result of the claimed peptide having the structure of EEG(X1)QD(X2)EPEA (SEQ ID NO:5) wherein X1 is Y and Y2 is F or W; or X1 is F or W and X2 is Y, F or W and being less than 30 amino acid residues in length and for treating synucleopathy including PD, LBD and MSA, and resulted in an improved product and a method for treating synucleopathy including PD, LBD and MSA.
Using and including the known a-SynP130-140 peptide mutants with mutations Y133F and/or Y136F, Y133W and/or Y136W and being less than 30 amino acids in length and the known method of active immunization of the a-SynP130-140 peptide mutants in the method and a-SynP130-140 peptide mutants of Ahlijanian and Kaylor would generate the claimed a-SynP130-140 peptide mutants with mutations Y133F and/or Y136F, Y133W and/or Y136W and being less than 30 amino acids in length for pharmaceutical purposes including active immunization and treatment of synucleopathy including PD, LBD and MSA, and expand application of the method and a-SynP130-140 peptide mutants of Ahlijanian and Kaylor in pharmaceutical purposes and treating diseases mediated a-synuclein including synucleopathy including PD, LBD and MSA.
Thus, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to apply the known a-SynP130-140 peptide or the known a-SynP130-140 peptide being less than 30 amino acids in length and the known method of active immunization and the known technique disclosed by Schenk to the method and a-SynP130-140 peptide mutants of Ahlijanian and Kaylor, and yield the predictable result of the claimed a-SynP130-140 peptide mutants with mutations Y133F and/or Y136F, Y133W and/or Y136W and being less than 30 amino acids and treating synucleopathy including PD, LBD and MSA.
The sequence search results disclose as follows:
SEQ ID NO:5-X1Y-X2F
US-12-037-081A-41
Sequence 41, US/12037081A
Patent No. 8092801
GENERAL INFORMATION
APPLICANT: Schenk, Dale B
APPLICANT: Masliah, Eliezer
APPLICANT: Buttini, Manuel J
APPLICANT: Chilcote, Tamie J
APPLICANT: Rockenstein, Edward
APPLICANT: Games, Kate D
TITLE OF INVENTION: PREVENTION AND TREATMENT OF SYNUCLEINOPATHIC AND AMYLOIDOGENIC
TITLE OF INVENTION: DISEASE
FILE REFERENCE: 015270-008980US
CURRENT APPLICATION NUMBER: US/12/037,081A
CURRENT FILING DATE: 2008-10-14
PRIOR APPLICATION NUMBER: US 11/697,646
PRIOR FILING DATE: 2007-04-06
PRIOR APPLICATION NUMBER: US 11/710,248
PRIOR FILING DATE: 2007-02-23
PRIOR APPLICATION NUMBER: US 60/984,721
PRIOR FILING DATE: 2007-11-01
NUMBER OF SEQ ID NOS: 86
SEQ ID NO 41
LENGTH: 13
TYPE: PRT
ORGANISM: Homo sapiens
FEATURE:
NAME/KEY: MOD_RES
LOCATION: (1)..(1)
OTHER INFORMATION: ACETYLATION
Xaa is acetylated Proline
Query Match 95.1%; Score 58; Length 13;
Best Local Similarity 90.9%;
Matches 10; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EEGYQDFEPEA 11
||||||:||||
Db 3 EEGYQDYEPEA 13
Conclusion
13. NO CLAIM IS ALLOWED.
Sequence alignment
SEQ ID NO:1(aa 1-140) 1 MDVFMKGLSKAKEGVVAAAEKTKQGVAEAAGKTKEGVLYVGSKTKEGVVHGVATVAEKTK 60
SEQ ID NO:2(aa 2-10) 1 -DVFMKGLSKA------------------------------------------------- 10
SEQ ID NO:1(aa 1-140) 61 EQVTNVGGAVVTGVTAVAQKTVEGAGSIAAATGFVKKDQLGKNEEGAPQEGILEDMPVDP 120
SEQ ID NO:3(aa 73-96) 1 ------------GVTAVAQKTVEGAGSIAAATGFVK------------------------ 24
SEQ ID NO:1(aa 1-140) 121 DNEAYEMPSEEGYQDYEPEA 140
SEQ ID NO:4(aa 130-140) 1 ---------EEGYQDYEPEA 11
SEQ ID NO:5(aa 130-140) 1 ---------EEGXQDXEPEA 11
SEQ ID NO:6(aa 121-140) 1 DNEAYEMPSEEGYQDYEPEA 20
SEQ ID NO:7(aa 131-140) 1 ----------EGYQDYEPEA 10
14. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Lee et al. (US11442069) teaches an a-SynP130-140 peptide having the structure of EEG(X1)QD(X2)EPEA (SEQ ID NO:5) wherein X1 is Y and X2 is Y (see the sequence alignment below).
SEQ ID NO:5-X1Y-X2W
US-13-985-301-25
(NOTE: this sequence has 3 duplicates in the database searched)
Sequence 25, US/13985301
Patent No. 11442069
GENERAL INFORMATION
APPLICANT: ATGen Co. Ltd.
TITLE OF INVENTION: METHOD OF DIAGNOSING CANCER AND DIAGNOSIS KIT USING MEASUREMENT
TITLE OF INVENTION: OF NK CELL ACTIVITY
FILE REFERENCE: 201371-078970-US
CURRENT APPLICATION NUMBER: US/13/985,301
CURRENT FILING DATE: 2013-08-14
PRIOR APPLICATION NUMBER: PCT/IB2012/000259
PRIOR FILING DATE: 2012-02-10
PRIOR APPLICATION NUMBER: KR 2011-0012983
PRIOR FILING DATE: 2011-02-14
NUMBER OF SEQ ID NOS: 29
SEQ ID NO 25
LENGTH: 11
TYPE: PRT
ORGANISM: Homo Sapien
FEATURE:
OTHER INFORMATION: human alpha synuclein / C-terminal acidic tail domain
residues 130-140
Query Match 86.4%; Score 57; Length 11;
Best Local Similarity 90.9%;
Matches 10; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EEGYQDWEPEA 11
||||||:||||
Db 1 EEGYQDYEPEA 11
SEQ ID NO:5-X1Y-X2F
US-13-985-301-25
(NOTE: this sequence has 3 duplicates in the database searched)
Sequence 25, US/13985301
Patent No. 11442069
GENERAL INFORMATION
APPLICANT: ATGen Co. Ltd.
TITLE OF INVENTION: METHOD OF DIAGNOSING CANCER AND DIAGNOSIS KIT USING MEASUREMENT
TITLE OF INVENTION: OF NK CELL ACTIVITY
FILE REFERENCE: 201371-078970-US
CURRENT APPLICATION NUMBER: US/13/985,301
CURRENT FILING DATE: 2013-08-14
PRIOR APPLICATION NUMBER: PCT/IB2012/000259
PRIOR FILING DATE: 2012-02-10
PRIOR APPLICATION NUMBER: KR 2011-0012983
PRIOR FILING DATE: 2011-02-14
NUMBER OF SEQ ID NOS: 29
SEQ ID NO 25
LENGTH: 11
TYPE: PRT
ORGANISM: Homo Sapien
FEATURE:
OTHER INFORMATION: human alpha synuclein / C-terminal acidic tail domain
residues 130-140
Query Match 95.1%; Score 58; Length 11;
Best Local Similarity 90.9%;
Matches 10; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EEGYQDFEPEA 11
||||||:||||
Db 1 EEGYQDYEPEA 11
Ahlijanian et al. (US11827695) teaches an a-SynP130-140 peptide having the structure of EEG(X1)QD(X2)EPEA (SEQ ID NO:5) wherein X1 is Y and X2 is Y (see the sequence alignment below).
SEQ ID NO:5-X1Y-X2W
Sequence 155, US/17152051
Patent No. 11827695
GENERAL INFORMATION
APPLICANT: BRISTOL-MYERS SQUIBB COMPANY
TITLE OF INVENTION: ANTIBODIES TO ALPHA-SYNUCLEIN AND USES THEREOF
FILE REFERENCE: MXI-554USCN
CURRENT APPLICATION NUMBER: US/17/152,051
CURRENT FILING DATE: 2021-01-19
PRIOR APPLICATION NUMBER: US 16/486,238
PRIOR FILING DATE: 2019-08-15
PRIOR APPLICATION NUMBER: PCT/US2018/000032
PRIOR FILING DATE: 2018-02-16
PRIOR APPLICATION NUMBER: US 62/460,416
PRIOR FILING DATE: 2017-02-17
NUMBER OF SEQ ID NOS: 182
SEQ ID NO 155
LENGTH: 11
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic: alpha-Syn 130-140
Query Match 86.4%; Score 57; Length 11;
Best Local Similarity 90.9%;
Matches 10; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EEGYQDWEPEA 11
||||||:||||
Db 1 EEGYQDYEPEA 11
Lee et al. (US2379384) teaches an a-SynP130-140 peptide having the structure of EEG(X1)QD(X2)EPEA (SEQ ID NO:5) wherein X1 is Y and X2 is Y (see the sequence alignment below).
SEQ ID NO:5-X1Y-X2W
Sequence 25, US/17691391
Patent No. 12379384
GENERAL INFORMATION
APPLICANT: ATGen Co. Ltd.
TITLE OF INVENTION: METHOD OF DIAGNOSING CANCER AND DIAGNOSIS KIT USING MEASUREMENT
TITLE OF INVENTION: OF NK CELL ACTIVITY
FILE REFERENCE: 201371-078970-US
CURRENT APPLICATION NUMBER: US/17/691,391
CURRENT FILING DATE: 2022-03-10
PRIOR APPLICATION NUMBER: PCT/IB2012/000259
PRIOR FILING DATE: 2012-02-10
PRIOR APPLICATION NUMBER: KR 2011-0012983
PRIOR FILING DATE: 2011-02-14
NUMBER OF SEQ ID NOS: 29
SEQ ID NO 25
LENGTH: 11
TYPE: PRT
ORGANISM: Homo Sapien
FEATURE:
OTHER INFORMATION: human alpha synuclein / C-terminal acidic tail domain
residues 130-140
Query Match 86.4%; Score 57; Length 11;
Best Local Similarity 90.9%;
Matches 10; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EEGYQDWEPEA 11
||||||:||||
Db 1 EEGYQDYEPEA 11
Kim et al. (US20050203010) teaches an a-SynP130-140 peptide having the structure of EEG(X1)QD(X2)EPEA (SEQ ID NO:5) wherein X1 is Y and X2 is Y (see the sequence alignment below).
SEQ ID NO:5-X1Y-X2W
AEC80356
(NOTE: this sequence has 7 duplicates in the database searched)
ID AEC80356 standard; peptide; 11 AA.
XX
AC AEC80356;
XX
DT 17-NOV-2005 (first entry)
XX
DE Human alpha-synuclein C-terminal acidic tail peptide fragment.
XX
KW environmental stress tolerance; alpha-synuclein.
XX
OS Homo sapiens.
XX
CC PN US2005203010-A1.
XX
CC PD 15-SEP-2005.
XX
CC PF 10-MAY-2005; 2005US-00908400.
XX
PR 14-NOV-2003; 2003US-00713851.
PR 11-MAY-2004; 2004KR-00033123.
PR 02-MAY-2005; 2005KR-00036882.
XX
CC PA (ATGE-) ATGEN CO LTD.
XX
CC PI Kim J;
XX
DR WPI; 2005-618151/63.
XX
CC PT New peptide comprising a peptide fragment containing a sequence
CC PT comprising 10 or more consecutive amino acid residues, useful in
CC PT conferring resistance to environmental stress to a protein of interest.
XX
CC PS Claim 3; SEQ ID NO 8; 100pp; English.
XX
CC The invention relates to a peptide conferring resistance to environmental
CC stress. The peptide comprises a peptide fragment containing a sequence
CC composed of 10 or more consecutive amino acid residues of the C-terminal
CC acidic tail of alpha-synuclein, beta-synuclein, gamma-synuclein or
CC synoretin. Also described: (1) a fusion protein comprising the peptide
CC and a fusion partner protein; and (2) a method of conferring resistance
CC to environmental stress to a protein of interest, comprising linking the
CC protein to the peptide. The peptide is useful in conferring resistance to
CC environmental stress to a protein of interest. The present sequence
CC represents a human alpha-synuclein C-terminal acidic tail peptide
CC fragment, which is used in the exemplification of the present invention.
XX
SQ Sequence 11 AA;
Query Match 86.4%; Score 57; Length 11;
Best Local Similarity 90.9%;
Matches 10; Conservative 1; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EEGYQDWEPEA 11
||||||:||||
Db 1 EEGYQDYEPEA 11
15. 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.
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Chang-Yu Wang
March 6, 2026
/CHANG-YU WANG/Primary Examiner, Art Unit 1675