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
Application Status
This application is a 371 of PCT/GB2020/052363, filed on 03/28/2022.
Claims 2, 6, 11-12, 14-17, 49-50, 53-57, 60, 70, and 79-80 are currently pending in the instant application.
The preliminary amendment filed on 11/21/2025, canceling claim 81 is acknowledged.
Election/Restriction
Applicant's election without traverse of Group I, claims 2, 6, 11-12, 14-17, 49-50, 53-57, 60, 70, and 79-80, drawn to a method for treating a neurological disorder in a subject, the method comprising administering a polypeptide to the subject, wherein the polypeptide comprises: (a) a clostridial neurotoxin light chain (L-chain) or fragment thereof, wherein the clostridial neurotoxin L-chain or fragment thereof is catalytically inactive; or (b) a fragment of a clostridial neurotoxin heavy chain (H-chain), wherein the fragment of the clostridial neurotoxin H-chain comprises a clostridial neurotoxin receptor binding domain (Hc domain) or fragment thereof, and wherein the polypeptide does not comprise both a clostridial neurotoxin translocation domain (HN domain) and a clostridial neurotoxin He domain, and neurotoxin protein of SEQ ID NO: 2 and encoded nucleic acid sequence of SEQ ID NO: 1 in the response filed on 11/21/2025 is acknowledged.
The requirement is still deemed proper and is therefore made FINAL.
Claims 2, 6, 11-12, 14-17, 49-50, 53-57, 60, 70, and 79-80 are present for examination.
Priority
Acknowledgement is made of applicants claim for foreign priority under 35 U.S.C. 119(a)-(d) to a foreign patent application UNITED KINGDOM 1914034.2, filed on 09/30/2020.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 03/28/2022, 01/30/2025, and 07/30/2025 are acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are considered by the examiner. The signed copies of 1449 are enclosed herewith.
Specification Objections
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (pg. 9, para 5, pg 27, para 4-5, pg 28, para 1, 3, pg 47, para 4). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code. See MPEP § 608.01.
Drawings
Drawings submitted on 03/28/2022 are accepted by the Examiner.
Claim Rejections - 35 USC § 112(b)
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.
Claim 80 (depends on claim 57, which depends on claim 2) is rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which applicant regards as the invention.
Claim 80 is indefinite in the recitation “the modified clostridial neurotoxin is a chimeric neurotoxin or a hybrid neurotoxin” lacks antecedent basis, and claims 57 or claim 2, does not recite anything about chimeric neurotoxin or a hybrid neurotoxin, and their scope of the invention, as well as the components, which are unknown, and thus unclear. Therefore, “the chimeric neurotoxin or a hybrid neurotoxin” lacks antecedent basis, in claim 57 or claim 2. Clarification is required.
Claim Rejections – Improper Markush Grouping
Claim 54 is rejected under the judicially approved “improper Markush grouping” doctrine. See Supplementary Examination Guidelines for Determining Compliance with 35 U.S.C. §112 and for Treatment of Related Issues in Patent Applications, 76 FR 7162 (Feb. 9, 2011), page 7166.
Claim 54 is “Markush”-type claims that recite a plurality of neuronal injury as species such as “nerve trauma --------and an injury to the branchial plexus”.
A Markush claim may be rejected under the judicially approved “improper Markush grouping” doctrine when the claim contains an improper grouping of alternatively useable species. A Markush claim contains an “improper Markush grouping” if: (1) The species of the Markush group do not share a “single structural similarity,” and (2) the species do not share a common use.
Claim 54 is rejected as reciting an improper Markush group because they do not share a structural similarity nor a common use. When an examiner determines that the species of a Markush group do not share a single structural similarity or do not share a common use, then a rejection on the basis that the claim contains an “improper Markush grouping” is appropriate. Claim 55 is rejected under the judicially approved “improper Markush grouping” doctrine. See Supplementary Examination Guidelines for Determining Compliance with 35 U.S.C. §112 and for Treatment of Related Issues in Patent Applications, 76 FR 7162 (Feb. 9, 2011), page 7166.
Claim 55 is “Markush”-type claims that recite a plurality of neurological diseases as species such as “Alzheimer’s disease --------and frontotemporal lobar degeneration.
A Markush claim may be rejected under the judicially approved “improper Markush grouping” doctrine when the claim contains an improper grouping of alternatively useable species. A Markush claim contains an “improper Markush grouping” if: (1) The species of the Markush group do not share a “single structural similarity,” and (2) the species do not share a common use.
Claim 55 is rejected as reciting an improper Markush group because they do not share a structural similarity nor a common use. When an examiner determines that the species of a Markush group do not share a single structural similarity or do not share a common use, then a rejection on the basis that the claim contains an “improper Markush grouping” is appropriate.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless -
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale or otherwise available to the public before the effective filing date of the claimed invention.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 2, 6, 11-12, 14-17, 49-50, 53-57, 60, 70, and 79-80 are rejected under 35 U.S.C. 102(a)(1) based upon a public use or sale or other public availability of the invention as anticipated by Araye et al. (The Translocation Domain of Botulinum Neurotoxin A Moderates the Propensity of the Catalytic Domain to Interact with Membranes at Acidic pH. PLOS ONE Vol 11(8), 1-20, 2018).
The Broadest Reasonable Interpretation (BRI) of claim 2, which is drawn to a method for treating a neurological disorder in a subject, the method comprising administering a polypeptide to the subject, wherein the polypeptide comprises:(a) a clostridial neurotoxin light chain (L-chain) or fragment thereof, wherein the clostridial neurotoxin L-chain or fragment thereof is catalytically inactive; or (b) a fragment of a clostridial neurotoxin heavy chain (H-chain), wherein the fragment of the clostridial neurotoxin H-chain comprises a clostridial neurotoxin receptor binding domain (Hc domain) or fragment thereof, and wherein the polypeptide does not comprise both a clostridial neurotoxin translocation domain (HN domain) and a Clostridial neurotoxin Hc domain (receptor binding domain) of H-chain.
Regarding claims 2, 6, 11-12, 14-17, 49-50, 53-57, 70, and 79-80, Araye et al. teach a recombinant, or engineered Botulinum neurotoxin A (BoNT/A) is composed of three domains: i) a catalytic domain (LC), ii) a translocation domain (HN) and iii) a receptor-binding domain (HC) without translocation domain (Hn) and receptor binding domain (Hc), wherein BoNT/A is an amphitropic protein, produced in soluble form, that is able to interact, penetrate and cross a membrane to achieve toxin function. A Botulinum neurotoxin A (BoNT/A) molecule is lacking the translocation domain (HL) and receptor-binding domain (HN), consists only of the 50 kDa Light Chain (LC), which is the zinc-dependent endopeptidase responsible for cleaving SNARE proteins specifically SNAP-25 for Serotype A, i.e., Botulinum neurotoxin A (BoNT/A) without translocation domain (HN) and receptor binding domain (HC), is in fact light chain (LC) of Botulinum neurotoxin A (BoNT/A) as claimed, in claim 2 (see, Schematic diagram of Botulinum neurotoxin A (BoNT/A) as shown below, and meets the claim limitation of claim 2.
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Araye et al. also teach that cloning , production, and purification of recombinant LC (light chain), HN (translocation domain) and tandem LC-HN. (see, pg 2, para 4, pg 3, para 2-6, pg 4, para 3, pg 5, para 2-3, pg 6, para 4, pg 11, para 1-2, Fig. 1, 2, 4, 5, 6, Table 1-3, and SnagIt image of Fig. 1 as shown below).
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Claims 6 and 15-16 are included in this rejection because LC fragment (without HN and HC domain) Botulinum neurotoxin (BoNT) is a protein as shown above, but Araye et al. do not teach clearly whether this fragment is catalytically inactive or active.
According to MPEP 2112.01- when structure recited in the reference is substantially identical to that of the claims, claimed properties, or functions or activity are presumed to be inherent.
2112.01 Composition, Product, and Apparatus Claims [R-07.2015]
I. PRODUCT AND APPARATUS CLAIMS — WHEN THE STRUCTURE RECITED IN THE REFERENCE IS SUBSTANTIALLY IDENTICAL TO THAT OF THE CLAIMS, CLAIMED PROPERTIES OR FUNCTIONS ARE PRESUMED TO BE INHERENT
Where the claimed and prior art products are identical or substantially identical in structure or composition, or are produced by identical or substantially identical processes, a prima facie case of either anticipation or obviousness has been established. In re Best, 562 F.2d 1252, 1255, 195 USPQ 430, 433 (CCPA 1977). “When the PTO shows a sound basis for believing that the products of the applicant and the prior art are the same, the applicant has the burden of showing that they are not.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). Therefore, the prima facie case can be rebutted by evidence showing that the prior art products do not necessarily possess the characteristics of the claimed product. In re Best, 562 F.2d at 1255, 195 USPQ at 433. See also Titanium Metals Corp.v. Banner, 778 F.2d 775, 227 USPQ 773 (Fed. Cir. 1985) (Claims were directed to a titanium alloy containing 0.2-0.4% Mo and 0.6-0.9% Ni having corrosion resistance. A Russian article disclosed a titanium alloy containing 0.25% Mo and 0.75% Ni but was silent as to corrosion resistance. The Federal Circuit held that the claim was anticipated because the percentages of Mo and Ni were squarely within the claimed ranges. The court went on to say that it was immaterial what properties the alloys had or who discovered the properties because the composition is the same and thus must necessarily exhibit the properties.).
Regarding Claim 2, examiner takes the position that treating neurological disorder is inherent property of the polypeptide of LC fragment. According to MPEP-
Because the LC fragment of BoNT/A of the claimed invention and that of the reference is one and the same, Examiner takes the position that the treating neurological disorder is inherent property of the polypeptide of LC fragment of BoNT/A of Araye et al. reference. Since the Office does not have the facilities for examining and comparing applicants' LC protein with the LC protein of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product (i.e. amount) and the product of the prior art (i.e., amount). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
2112.01- when structure recited in the reference is substantially identical to that of the claims, claimed properties, or functions or activity are presumed to be inherent.
Besides: MPEP: Form Paragraph 7.37.10 states that “A preamble is generally not accorded any patentable weight where it merely recites the purpose of a process or the intended use of a structure, and where the body of the claim does not depend on the preamble for completeness but, instead, the process steps or structural limitations are able to stand alone. See In re Hirao, 535 F.2d 67, 190 USPQ 15 (CCPA 1976) and Kropa v. Robie, 187 F.2d 150, 152, 88 USPQ 478, 481 (CCPA 1951).
Regarding claim 12, Araye et al. BoNT/A protein fragments included LC, HN and LC-HN and thus, said protein lacks HCc domain.
Regarding claim 14, Araye et al. BoNT/A protein fragments included LC, HN and LC-HN and thus, said protein lacks non-clostridial catalytic domain.
Claims 15-16 are included in this rejection because LC fragment (without HN and HC domain) Botulinum neurotoxin (BoNT) is a protein as shown above, but Araye et al. do not teach clearly whether this fragment is catalytically inactive or active. Araye et al. also teach HN fragment of BoNT/A (see, Fig. 2 and Table 1).
Regarding claim 49, Araye et al. BoNT/A protein fragments included LC, HN and LC-HN and thus, said protein fragment of LC lacks a H chain.
Regarding Claims 50, 56, for the polypeptide having neurotrophic function and promotes growth or repair of the motor neuron, or administered are the inherent property of the polypeptide of LC fragment. According to MPEP-
Because the LC fragment having neurotropic function and promotes growth or repair of the motor neuron of BoNT/A of the claimed invention and that of the reference is one and the same, Examiner takes the position that the LC fragment having neurotropic function and promotes growth or repair of the motor neuron of BoNT/A are the inherent property of the polypeptide of LC fragment of BoNT/A of Araye et al. reference. Since the Office does not have the facilities for examining and comparing applicants' LC protein with the LC protein of the prior art, the burden is on the applicant to show a novel or unobvious difference between the claimed product (i.e. amount) and the product of the prior art (i.e., amount). See In re Best, 562 F.2d 1252, 195 USPQ 430 (CCPA 1977) and In re Fitzgerald et al., 205 USPQ 594.
Besides, the statements of intended use for the claimed polypeptide recited in claims 53, 54, and 55 and 70 (due to the recitation of various neuronal disease, site of administered are noted. However, M.P.E.P. § 2111.02 reads, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention's limitations, then the preamble is not considered a limitation and is of no significance to claim construction.”
Regarding claim 57, Araye et al. indeed teach LC fragment is a recombinant Clostridial protein.
Regarding claim 60 is out prior art.
Regarding claim 70, Besides, the statements of intended use for the claimed polypeptide recited in claims 53, 54, and 55 and 70 (due to the recitation of various neuronal disease, site of administered are noted. However, M.P.E.P. § 2111.02 reads, “If the body of a claim fully and intrinsically sets forth all of the limitations of the claimed invention, and the preamble merely states, for example, the purpose or intended use of the invention, rather than any distinct definition of any of the claimed invention's limitations, then the preamble is not considered a limitation and is of no significance to claim construction.”
Regarding claims 79, The BoNT/A protein of Araye et al. indeed a recombinant chimeric or clostridial neurotoxin protein comprises LC, HN and HC domains.
Therefore, Araye et al. anticipate claims 2, 6, 11-12, 14-17, 49-50, 53-57, 70, and 79-80 of the instant application as written.
Conclusion
Status of the claims:
Claims 2, 6, 11-12, 14-17, 49-50, 53-57, 70, and 79-80 are rejected.
Claim 60 is objected to as depends from rejected base claim 2.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to IQBAL H CHOWDHURY whose telephone number is (571)272-8137. The examiner can normally be reached on M-F, at 9:00-5:00 PM.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Manjunath N. Rao, can be reached on 571-272-0939. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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Iqbal H. Chowdhury, Primary Examiner
Art Unit 1656 (Recombinant Enzymes and Protein Crystallography)
US Patent and Trademark Office
Ph. (571)-272-8137 and Fax (571)-273-8137
/IQBAL H CHOWDHURY/
Primary Examiner, Art Unit 1656