DETAILED ACTION
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 .
Status of Claims
Claims 1-8, 14-21, 30-31, and 43-44 are currently pending.
Claims 1-8 and 14-21 are under consideration, as claims 30-31 and 43-44 are withdrawn.
Election/Restrictions
Applicant’s election of Group I (i.e., claims 1-8 and 14-21. Drawn to a fusion protein comprising a PH domain and BoNT/E light chain, and nucleic acids encoding said proteins) and SEQ ID NO: 5 (Genus A: fusion protein sequence), SEQ ID NO: 12 (Genus B: PTEN sequence), and SEQ ID NO: 16 (Genus C: SNAP25 sequence) in the reply filed on 11/14/2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 30-31 and 43-44 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 11/14/2025.
Priority
The present application claims status as a 371 (National Stage) of PCT/US21/64125 filed on 12/17/2021. Acknowledgment is made of applicant’s claim for benefit under 35 U.S.C. 119(e) of Provisional application No. 63/127,340, filed on 12/18/2020. The present application and all claims are being examined with an effective filing date of 12/18/2020. In future actions, the effective filing date may change due to amendments or further review of priority documents.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 09/15/2023, 01/05/2024, and 11/14/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements have been considered by the examiner.
Claim Rejections - 35 USC § 112(a)
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 1-7 and 14-21 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
It is noted that MPEP 2111.01 states that ''[d]uring examination, the claims must be interpreted as broadly as their terms reasonably allow. Claim 1 has been broadly interpreted as encompassing a genus of fusion proteins comprising any PH domain, and a BoNT/E protease light chain having at least 80% sequence identity to SEQ ID NO: 1, regardless of whether the LC retains catalytic activity, PTEN cleavage activity, loss of SNAP25 cleavage, altered substrate specificity, or any other functional property. Claims 2-7 further expand the genus through PH domains that are at least 80% identical to SEQ ID NO: 2, BoNT/E LCs bearing any one of dozens of substitutions relative to SEQ ID NO: 1, or fusion proteins having at least 80% identity to SEQ ID NOs: 5 or 6. Claim 14 requires catalytic activity. Claims 15–16 require cleavage of a noncanonical substrate, including PTEN. Claim 17 introduces PTEN sequences having at least 70% sequence identity to SEQ ID NOs: 12 or 13. Claims 18–19 require loss of SNAP protein or SNAP25 cleavage. Claim 20 introduces SNAP25 sequences with 80% identity to SEQ ID NO: 16 or 17. And claim 21 encompasses a genus of nucleic acids encoding a genus of fusion proteins comprising a PH domain, and a BoNT/E protease light chain having at least 80% sequence identity to SEQ ID NO: 1, regardless of whether the LC retains catalytic activity, PTEN cleavage activity, loss of SNAP25 cleavage, altered substrate specificity, or any other functional property.
MPEP 2163 I. states that 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.
MPEP 2163. II.A.3.(a) states that “Possession may be shown in many ways. For example, possession may be shown by describing an actual reduction to practice of the claimed invention. Possession may also be shown by a clear depiction of the invention in detailed drawings or in structural chemical formulas which permit a person skilled in the art to clearly recognize that inventor had possession of the claimed invention. An adequate written description of the invention may be shown by any description of sufficient, relevant, identifying characteristics so long as a person skilled in the art would recognize that the inventor had possession of the claimed invention.
According to MPEP 2163.II.A.3.(a).ii), “Satisfactory disclosure of a ‘representative number’ depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art (including protein engineering), adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus…Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are ‘representative of the full variety or scope of the genus,’ or by the establishment of ‘a reasonable structure-function correlation.’"
In the instant case, the specification provides several exemplary sequences, including: wild-type BoNT/E LC (SEQ ID NO: 1), engineered BoNT/E variants (SEQ ID NOs: 3–4), two fusion constructs (SEQ ID NOs: 5–6), several PH domain sequences (SEQ ID NOs: 2, 7, 18–21), nucleic acid sequences encoding these proteins (SEQ ID NOs: 7–11, 22–26), PTEN sequences (SEQ ID NOs: 12–13), and SNAP25 sequences (SEQ ID NOs: 16–17). While this constitutes disclosure of several species, the specification does not identify which residues of BoNT/E LC are essential for catalytic activity, which residues are essential for PTEN cleavage, which residues must be preserved to eliminate SNAP25 cleavage, which parts of the LC determine intracellular targeting, or how the structure–function relationship is maintained across sequences sharing only 80% identity to SEQ ID NO: 1. Given that the primary amino acid sequence determines protein structure and function, the breadth of the claimed genus encompasses a wide range of possible structural variants throughout the molecule. There is no guidance that would allow a skilled artisan to reliably predict which variants within the broad identity-based genera would retain the recited functions. Thus, although the specification discloses specific species, it does not articulate common structural features possessed by the members of the claimed genera.
It is noted, however, that the specification discloses multiple PH domains (SEQ ID NOs: 2, 7, 18–21), and therefore provides a more substantial representative sampling. Accordingly, the written description deficiency does not arise from the PH domain portion of the fusion protein but from the BoNT/E LC portion and the functional requirements imposed by dependent claims. The specification does not describe or identify which LC residues are critical for protease activity, which residues are required for PTEN recognition or cleavage, which sequence features produce loss of SNAP25 cleavage, or how any of these functional attributes correlate with up to 20% sequence variation permitted by the claims. Although several LC variants are disclosed, they are limited to specific substitutions and do not establish what structural characteristics define the genus. There is no explanation of allowable vs. non-allowable mutations, no conserved-residue mapping, and no structure–function rationale enabling prediction across the claimed breadth. Thus, the disclosure does not demonstrate possession of the full genus of LC variants recited by claims 1 and 4-7, nor of the functional subsets recited by claims 14-15.
With respect to claim 17, a 30% divergence in PTEN, an enzyme with defined structural domains and active-site constraints, represents a broad genus. As stated above, the specification discloses SEQ ID NO: 12 (a full length PTEN sequence) and SEQ ID NO: 13 (a minimized cleavage sequence). However, it does not identify which PTEN residues must be preserved for recognition or cleavage by the BoNT/E LC, nor does it provide guidance enabling prediction of which 70% identity variants would remain within the functional scope of the claim. With respect to claims 18-20, as stated above, the specification discloses a full SNAP25 sequence (SEQ ID NO: 16), and a minimized cleavage sequence (SEQ ID NO: 17). These sequences identify key substrate regions, but the specification does not specify which SNAP25 residues must be preserved for recognition vs. inhibition of cleavage, identify the structural requirements for loss of cleavage activity, provide mutational maps, or describe how 80% identity variants would interact with BoNT/E LCs. Although the minimized cleavage sequence identifies a functionally relevant region, it does not constitute a structure–function correlation sufficient to support the full genus of 80% identity SNAP25 variants of claim 20 or the functional negative limitation of claims 18-19.
Regarding claim 21, because the specification does not demonstrate possession of the full breadth of the encoded proteins (for claim 1), it likewise does not demonstrate possession of nucleic acids encoding them.
In the absence of such structural or functional characterization, one of ordinary skill in the art would not be able to visualize or recognize the identity of the members of the genus encompassed by the claims without undue experimentation. Given this lack of description of the representative species encompassed by the genus of the claims, the specification fails to sufficiently describe the claimed invention in such full, clear, concise, and exact terms that a skilled artisan would recognize that applicants were in possession of the full scope of the invention of claims 1-7 and 14-21.
The dependent claims do not remedy the deficiencies noted above. Although certain dependent claims recite specific substitutions, identity thresholds, PH domains, or substrate preferences, these limitations do not provide structural or functional detail sufficient to demonstrate possession of the full breadth of the BoNT/E light-chain genus, the PH-BoNT/E LC fusion genus, the PTEN genus, or the SNAP25-related sequences encompassed by the independent claims. Accordingly, the dependent claims remain unpatentable for the reasons set forth above.
Claim Rejections - 35 USC § 103
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 (i.e., changing from AIA to pre-AIA ) 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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries 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 1-5, 7, 14-18, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Packer et al. (US Patent No. 12060553B2, cited in the IDS), Chaddock et al. (US Patent No. 9849163 B2, cited in a previous office action), Lemmon, M. (Pleckstrin homology (PH) domains and phosphoinositides. Biochem Soc Symp. 2007; (74):81-93, cited in a previous office action), and Yonghong, X. (US Patent No. 7049089 B2, cited in PTO-892).
Regarding claims 1-2, 4-5, 14-16, and 21, Packer et al. teaches Botulinum neurotoxin (BoNT) protease variants that cleave intracellular proteins (inherently catalytically active), including noncanonical BoNT cleavage substrates such as PTEN, wherein the variant comprises the light chain (LC), or both the LC and heavy chain (HC), and nucleic acid sequence encoding said protease, incorporated into a replicating vector and expressed in host cells (columns 111-112). More specifically, Packer et al. discloses BoNT E (serotype E) variants that cleave PTEN (Abstract and Specification columns 1-2, “Summary”). Packer et al. further teaches “unique BoNT E mutations, including I232T (column 29, Table 1), and discloses an exemplary variant set forth in SEQ ID NO: 5, comprising an I232T substitution, having 99.3% sequence identity to instant SEQ ID NO: 1 (see sequence alignment below). Additionally, Packer et al. discloses several variants comprising a I232T substitution that cleaves PTEN (Fig. 33 and Table 7). Thus, Packer et al. establishes that BoNT/E light chain proteases can be engineered to retain intracellular proteolytic activity against cytosolic or membrane-proximal substrates. While Packer et al. specifically teaches BoNT/E LC polypeptides having selectivity towards intracellular membrane-associated substrates, Packer et al. does not disclose a fusion protein comprising the BoNT/E LC and a pleckstrin homology (PH) domain.
Chaddock et al. teaches that non-cytotoxic proteases, including botulinum toxin light-chain proteases, were known to require access to intracellular, membrane associated SNARE substrates to exert their biological function, i.e., proteolysis. It is noted, SNARE substrates are membrane associated proteins that reside at intracellular membranes. Chaddock et al. further teaches that such proteases may be retargeted through modification with heterologous “targeting moieties” that mediate intracellular localization and substrate access. Thus, a person of ordinary skill in the art would have recognized that fusion of a targeting domain to a BoNT/E LC protease would represent an established method of altering where the protease acts intracellularly.
Lemmon teaches that pleckstrin homology (PH) domains bind specific phosphoinositides present in cellular membranes and, in certain classes, function to localize their host proteins to particular cellular membranes. Lemmon discloses that recognition of phosphoinositide headgroups by PH domains occurs in cellular membranes and that this interaction can direct proteins to defined intracellular membrane compartments (Background). Lemmon further teaches that a subset of PH domains bind phosphoinositides with high affinity and specificity and, as a result, “drive their host proteins to particular cellular membranes in a way that can be precisely regulated” (Conclusions). Lemmon additionally discloses that certain PH domains localize proteins to specific intracellular compartments, such as the Golgi, where phospholipid and protein targets co-exist (Targeting of OSBP/FAPP1/Osh Family PH Domains to the Golgi). Thus, Lemmon establishes that PH domains are well-understood protein segments used to mediate protein targeting to specific cellular membranes, and may be used to direct proteins to defined intracellular targets. Accordingly, a person of ordinary skill in the art would have recognized PH domains as suitable targeting moieties for incorporation into engineered protein constructs where altered or improved intracellular localization is desired.
Yonghong teaches DNA sequences encoding the human phospholipase-C delta-1 polypeptide and specifically identifies the isolated pleckstrin homology domain shown in Fig. 1 as an independently functioning segment of the protein (Specification, columns 8-10 and Fig. 1, 3, 5-8 and 10 for DNA sequences). Yonghong explicitly teaches fusion proteins in which the PLC delta-1 PH domain containing segment is covalently joined to heterologous full-length proteins or biologically active fragments, wherein the fusion proteins are constructed for functional assays and localization based applications (columns 16-18). Therefore, Yonghong teaches that the PLC delta-1 PH domain constitutes a modular, transferable protein segment suitable for incorporation into fusion constructs for altering intracellular localization characteristics of the resulting protein.
An invention would have been obvious to a person of ordinary skill in the art if some teaching in the prior art would have led that person to combine prior art reference teachings to arrive at the claimed invention. Before the effective filing date of the claimed invention, in view of Lemmon’s teaching that certain PH domains function to localize proteins to specific phosphoinositide-enriched cellular membranes where lipid and protein targets coexist, and Chaddock et al.’s teaching that botulinum toxin light-chain proteases require access to intracellular, membrane-associated substrates to exert proteolytic activity, it would have been obvious to a person of ordinary skill in the art that fusion of a PH domain to a BoNT/E light-chain protease would bias the protease toward membrane compartments where its substrates reside, representing a predictable and established strategy for altering intracellular localization of a protease. It would further be obvious to substitute the variant BoNT/E proteases (I232T) of Packer et al. for those of Chaddock et al., within the obvious fusion constructs, because Packer et al. teaches BoNT/E LC variants (I232T) engineered to cleave noncanonical intracellular substrates, such as PTEN, while Chaddock et al. teaches that such proteases may be retargeted through modification with heterologous targeting moieties (e.g., pleckstrin homology domains). Furthermore, because fusion proteins are routinely generated by constructing nucleic acids encoding the fused protein domains, a person of ordinary skill in the art would have found it obvious to generate a nucleic acid encoding a fusion protein comprising a PH domain and BoNT/E LC having at least 80% sequence identity to SEQ ID NO: 1, in view of Packer et al. and Yonghong’s disclosures of nucleic acid sequences encoding the respective components. Given the teachings of Yonghong, which successfully demonstrate that PH domains constitute independently functioning protein segments suitable for fusion to heterologous proteins or fragments, said practitioner would have reasonably expected that the combination of teachings would successfully result in a fusion protein according to claim 1, with a reasonable expectation of success. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claim 3, one of skill in the art before the effective filing date would have been motivated to use PH domains taught by Yonghong disclosed a PLC delta-1 set forth in SEQ ID NO: 11, having 95.3% sequence identity to instant SEQ ID NO: 2 (see sequence alignment below) as a part of the above obvious fusion proteins.
Regarding claim 7, as indicated above, Yonghong discloses a PLC delta-1 polypeptide including a PH domain set forth in SEQ ID NO: 11, and Packer et al. discloses a BoNT/E LC protease variant set forth in SEQ ID NO: 5. When the PH domain sequence of Yonghong is combined with the variant BoNT/E light chain sequence of Packer et al., the resulting construct exhibits approximately 95% sequence identity to instant SEQ ID NO: 5 (see sequence alignment below). In view of the teachings of Packer et al., Lemmon, Yonghong and Chaddock et al. above, it would have been obvious to a person of ordinary skill in the art to incorporate the PH domain containing region of Yonghong into the BoNT/E variant of Packer et al. to generate a fusion protein having intracellular location characteristics attributable to the PH domain segment. Accordingly, one of skill in the art before the time of invention would have been motivated to combine the Yonghong PLC delta-1 polypeptide including a PH domain set forth in SEQ ID NO: 11, and Packer et al.’s BoNT/E LC protease variant set forth in SEQ ID NO: 5, resulting in a “fusion construct” which has approximately 95% sequence identity to instant SEQ ID NO: 5. Therefore, the invention as a whole would have been prima facie obvious to a person of ordinary skill in the art before the effective filing date of the claimed invention.
Regarding claim 17, claim 17 is included in the obvious fusion proteins because as described above, Packer et al. discloses a BoNT/E LC variant capable of cleaving PTEN. Packer et al. further teaches wherein the PTEN comprises the amino acid sequence set forth in SEQ ID NO: 294 (column 4), which has 100% sequence identity to instant SEQ ID NO: 12 (see sequence alignment below. Note: Packer et al. is listed as a duplicate of Result 1).
Regarding claim 18, as evidenced by Packer et al., and Chaddock et al. the wild-type BoNT/E LC (disclosed by Packer et al. in SEQ ID NO: 286), set forth in instant SEQ ID NO: 1, cleaves the canonical substrate SNAP-25, but does not cleave SNAP-23 (Fig. 28 and Fig. 31). Packer et al. discloses BoNT/E protease variants that have been specifically engineered to cleave SNAP-23 (e.g., SEQ ID NO: 293), and variants specifically engineered to cleave other substrates (e.g., SEQ ID NO: 293 cleaves SNAP-25, but not SNAP-23) – see Fig. 31. Therefore, Packer et al. discloses both a wild-type BoNT E that inherently does not cleave a SNAP protein, and also variants that do not cleave a SNAP protein.
Thus, claims 1-5, 7, 14-18, and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Packer et al., Chaddock et al., Lemmon, and Yonghong, X.
Sequence alignment between SEQ ID NO: 5 of Packer et al. and instant SEQ ID NO: 1
US-16-641-630-5
Sequence 5, US/16641630
Patent No. 12060553
GENERAL INFORMATION
APPLICANT: President and Fellows of Harvard College
APPLICANT: Ipsen BioPharm Ltd
TITLE OF INVENTION: EVOLUTION OF BONT PEPTIDASES
FILE REFERENCE: H0824.70299US00
CURRENT APPLICATION NUMBER: US/16/641,630
CURRENT FILING DATE: 2020-02-24
PRIOR APPLICATION NUMBER: PCT/US2018/048134
PRIOR FILING DATE: 2018-08-27
PRIOR APPLICATION NUMBER: US 62/550,408
PRIOR FILING DATE: 2017-08-25
NUMBER OF SEQ ID NOS: 401
SEQ ID NO 5
LENGTH: 411
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic polypeptide
Query Match 99.3%; Score 2149; Length 411;
Best Local Similarity 99.3%;
Matches 408; Conservative 1; Mismatches 2; Indels 0; Gaps 0;
Qy 1 MPKINSFNYNDPVNDRTILYIKPGGCQEFYKSFNIMKNIWIIPERNVIGTTPQDFHPPTS 60
|||||||||||||||||||||||||||:||||||||||||||||||||||||||||||||
Db 1 MPKINSFNYNDPVNDRTILYIKPGGCQKFYKSFNIMKNIWIIPERNVIGTTPQDFHPPTS 60
Qy 61 LKNGDSSYYDPNYLQSDEEKDRFLKIVTKIFNRINNNLSGGILLEELSKANPYLGNDNTP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 LKNGDSSYYDPNYLQSDEEKDRFLKIVTKIFNRINNNLSGGILLEELSKANPYLGNDNTP 120
Qy 121 DNQFHIGDASAVEIKFSNGSQHILLPNVIIMGAEPDLFETNSSNISLRNNYMPSNHGFGS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 DNQFHIGDASAVEIKFSNGSQHILLPNVIIMGAEPDLFETNSSNISLRNNYMPSNHGFGS 180
Qy 181 IAIVTFSPEYSFRFNDNSINEFIQDPALTLMHELIHSLHGLYGAKGITTTCIITQQQNPL 240
|||||||||||||||||||||||||||||||||||||||||||| |||||| ||||||||
Db 181 IAIVTFSPEYSFRFNDNSINEFIQDPALTLMHELIHSLHGLYGAHGITTTCTITQQQNPL 240
Qy 241 ITNRKGINIEEFLTFGGNDLNIITVAQYNDIYTNLLNDYRKIASKLSKVQVSNPQLNPYK 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 ITNRKGINIEEFLTFGGNDLNIITVAQYNDIYTNLLNDYRKIASKLSKVQVSNPQLNPYK 300
Qy 301 DIFQEKYGLDKDASGIYSVNINKFDDILKKLYSFTEFDLATKFQVKCRETYIGQYKYFKL 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 DIFQEKYGLDKDASGIYSVNINKFDDILKKLYSFTEFDLATKFQVKCRETYIGQYKYFKL 360
Qy 361 SNLLNDSIYNISEGYNINNLKVNFRGQNANLNPRIIKPITGRGLVKKIIRF 411
|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 SNLLNDSIYNISEGYNINNLKVNFRGQNANLNPRIIKPITGRGLVKKIIRF 411
Sequence alignment between SEQ ID NO: 11 of Yonghong and instant SEQ ID NO: 2
US-10-276-339-11
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
Sequence 11, US/10276339
Patent No. 7049089
GENERAL INFORMATION
APPLICANT: Bayer AG
TITLE OF INVENTION: REGULATION OF HUMAN PLC DELTA-1
FILE REFERENCE: Lio074 Foreign Countries
CURRENT APPLICATION NUMBER: US/10/276,339
CURRENT FILING DATE: 2002-11-27
PRIOR APPLICATION NUMBER: US 60/207,277
PRIOR FILING DATE: 2000-05-30
PRIOR APPLICATION NUMBER: ATT. DOCKET NO. 298
PRIOR FILING DATE: 2001-03-27
NUMBER OF SEQ ID NOS: 13
SEQ ID NO 11
LENGTH: 756
TYPE: PRT
ORGANISM: Rattus norvegicus
Query Match 95.9%; Score 864; Length 756;
Best Local Similarity 95.3%;
Matches 162; Conservative 5; Mismatches 3; Indels 0; Gaps 0;
Qy 1 MDSGRDFLTLHGLQDDEDLQALLKGSQLLKVKSSSWRRERFYKLQEDCKTIWQESRKVMR 60
|||||||||||||||| |||||||||||||||||||||||||||||||||||||||||||
Db 1 MDSGRDFLTLHGLQDDPDLQALLKGSQLLKVKSSSWRRERFYKLQEDCKTIWQESRKVMR 60
Qy 61 TPESQLFSIEDIQEVRMGHRTEGLEKFARDVPEDRCFSIVFKDQRNTLDLIAPSPADAQH 120
:|||||||||||||||||||||||||||||:|||||||||||||||||||||||||||||
Db 61 SPESQLFSIEDIQEVRMGHRTEGLEKFARDIPEDRCFSIVFKDQRNTLDLIAPSPADAQH 120
Qy 121 WVLGLHKIIHHSGSMDQRQKLQHWIHSCLRKADKNKDNKMSFKELQNFLK 170
|| || ||||||||||||||||||||||||||||||||||:||||::|||
Db 121 WVQGLRKIIHHSGSMDQRQKLQHWIHSCLRKADKNKDNKMNFKELKDFLK 170
Sequence alignment between combined sequences of Packer et al. (SEQ ID NO: 5) and Yonghong (SEQ ID NO: 11) with instant SEQ ID NO: 5
OM protein - protein search, using sw model
Run on: December 10, 2025, 11:48:45 ; Search time 1 Seconds
(without alignments)
0.340 Million cell updates/sec
Title: AASEQ1_12102025_114844
Perfect score: 3070
Sequence: 1 MDSGRDFLTLHGLQDDPDLQ..........NPRIIKPITGRGLVKKIIRF 581
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 586 residues
Total number of hits satisfying chosen parameters: 1
Minimum DB seq length: 0
Maximum DB seq length: inf
Post-processing: Minimum Match 0%
Maximum Match 100%
Listing first 1 summaries
Database : US-18-268-178-5.pep:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 2916.5 95.0 586 1 US-18-268-178-5 EVOLUTION OF BOTUL
ALIGNMENTS
RESULT 1
US-18-268-178-5
Query Match 95.0%; Score 2916.5; DB 1; Length 586;
Best Local Similarity 94.9%;
Matches 556; Conservative 11; Mismatches 14; Indels 5; Gaps 1;
Qy 1 MDSGRDFLTLHGLQDDPDLQALLKGSQLLKVKSSSWRRERFYKLQEDCKTIWQESRKVMR 60
|||||||||||||||| |||||||||||||||||||||||||||||||||||||||||||
Db 1 MDSGRDFLTLHGLQDDEDLQALLKGSQLLKVKSSSWRRERFYKLQEDCKTIWQESRKVMR 60
Qy 61 SPESQLFSIEDIQEVRMGHRTEGLEKFARDIPEDRCFSIVFKDQRNTLDLIAPSPADAQH 120
:|||||||||||||||||||||||||||||:|||||||||||||||||||||||||||||
Db 61 TPESQLFSIEDIQEVRMGHRTEGLEKFARDVPEDRCFSIVFKDQRNTLDLIAPSPADAQH 120
Qy 121 WVQGLRKIIHHSGSMDQRQKLQHWIHSCLRKADKNKDNKMNFKELKDFLK-----MPKIN 175
|| || ||||||||||||||||||||||||||||||||||:||||::||| |||||
Db 121 WVLGLHKIIHHSGSMDQRQKLQHWIHSCLRKADKNKDNKMSFKELQNFLKGGGGSMPKIN 180
Qy 176 SFNYNDPVNDRTILYIKPGGCQKFYKSFNIMKNIWIIPERNVIGTTPQDFHPPTSLKNGD 235
|||||||||||||||||||| :|||||||||||||||||||||||||||||||||||||
Db 181 SFNYNDPVNDRTILYIKPGGYHEFYKSFNIMKNIWIIPERNVIGTTPQDFHPPTSLKNGD 240
Qy 236 SSYYDPNYLQSDEEKDRFLKIVTKIFNRINNNLSGGILLEELSKANPYLGNDNTPDNQFH 295
|||||||||||||||||||||||||||||||||:| ||||||||||||||||:|||||||
Db 241 SSYYDPNYLQSDEEKDRFLKIVTKIFNRINNNLAGSILLEELSKANPYLGNDDTPDNQFH 300
Qy 296 IGDASAVEIKFSNGSQHILLPNVIIMGAEPDLFETNSSNISLRNNYMPSNHGFGSIAIVT 355
||||||||||||||||||||||||||||||:|| | |||||||| |||||||||||||
Db 301 IGDASAVEIKFSNGSQHILLPNVIIMGAEPNLFLTYQRNISLRNNYKPSNHGFGSIAIVT 360
Qy 356 FSPEYSFRFNDNSINEFIQDPALTLMHELIHSLHGLYGAHGITTTCTITQQQNPLITNRK 415
||||||||||||||||||||||||||||||||||||||| ||||||||||||||||||||
Db 361 FSPEYSFRFNDNSINEFIQDPALTLMHELIHSLHGLYGAKGITTTCTITQQQNPLITNRK 420
Qy 416 GINIEEFLTFGGNDLNIITVAQYNDIYTNLLNDYRKIASKLSKVQVSNPQLNPYKDIFQE 475
|| |||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 GIKIEEFLTFGGNDLNIITVAQYNDIYTNLLNDYRKIASKLSKVQVSNPQLNPYKDIFQE 480
Qy 476 KYGLDKDASGIYSVNINKFDDILKKLYSFTEFDLATKFQVKCRETYIGQYKYFKLSNLLN 535
||||||||||||||||||||||||||||||||||||||||||||||||: |:||||||||
Db 481 KYGLDKDASGIYSVNINKFDDILKKLYSFTEFDLATKFQVKCRETYIGRPKFFKLSNLLN 540
Qy 536 DSIYNISEGYNINNLKVNFRGQNANLNPRIIKPITGRGLVKKIIRF 581
||||||||||||||||||||||||||||||||||||||||||||||
Db 541 DSIYNISEGYNINNLKVNFRGQNANLNPRIIKPITGRGLVKKIIRF 586
Sequence alignment between SEQ ID NO: 294 of Packer et al. and instant SEQ ID NO: 12
RESULT 1
US-08-791-115B-1
(NOTE: this sequence has 75 duplicates in the database searched.
See complete list at the end of this report)
Sequence 1, US/08791115B
Patent No. 6262242
GENERAL INFORMATION
APPLICANT: Steck, Peter
APPLICANT: Pershouse, Mark A.
APPLICANT: Jasser, Samar
APPLICANT: Yung, W.K. Alfred
APPLICANT: Tavtigian, Sean V.
TITLE OF INVENTION: A TUMOR SUPPRESSOR DESIGNATED TS10Q23.3
CURRENT APPLICATION NUMBER: US/08/791,115B
CURRENT FILING DATE: 30-JAN-1997
PRIOR APPLICATION NUMBER: NAME Ihnen, Jeffrey L.
PRIOR FILING DATE: REGISTRATION NUMBER 38,957
NUMBER OF SEQ ID NOS: 27
SEQ ID NO 1
LENGTH: 403
TYPE: PRT
Query Match 100.0%; Score 2184; Length 403;
Best Local Similarity 100.0%;
Matches 403; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MTAIIKEIVSRNKRRYQEDGFDLDLTYIYPNIIAMGFPAERLEGVYRNNIDDVVRFLDSK 60
Qy 61 HKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 HKNHYKIYNLCAERHYDTAKFNCRVAQYPFEDHNPPQLELIKPFCEDLDQWLSEDDNHVA 120
Qy 121 AIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSY 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 AIHCKAGKGRTGVMICAYLLHRGKFLKAQEALDFYGEVRTRDKKGVTIPSQRRYVYYYSY 180
Qy 181 LLKNHLDYRPVALLFHKMMFETIPMFSGGTCNPQFVVCQLKVKIYSSNSGPTRREDKFMY 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 LLKNHLDYRPVALLFHKMMFETIPMFSGGTCNPQFVVCQLKVKIYSSNSGPTRREDKFMY 240
Qy 241 FEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNTFFIPGPEETSEKVENGSLCDQEI 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 FEFPQPLPVCGDIKVEFFHKQNKMLKKDKMFHFWVNTFFIPGPEETSEKVENGSLCDQEI 300
Qy 301 DSICSIERADNDKEYLVLTLTKNDLDKANKDKANRYFSPNFKVKLYFTKTVEEPSNPEAS 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 DSICSIERADNDKEYLVLTLTKNDLDKANKDKANRYFSPNFKVKLYFTKTVEEPSNPEAS 360
Qy 361 SSTSVTPDVSDNEPDHYRYSDTTDSDPENEPFDEDQHTQITKV 403
|||||||||||||||||||||||||||||||||||||||||||
Db 361 SSTSVTPDVSDNEPDHYRYSDTTDSDPENEPFDEDQHTQITKV 403
DUPLICATE:
US-16-641-630-294
Filing date in PALM: 2020-02-24
Sequence 294, US/16641630
Patent No. 12060553
GENERAL INFORMATION
APPLICANT: President and Fellows of Harvard College
APPLICANT: Ipsen BioPharm Ltd
TITLE OF INVENTION: EVOLUTION OF BONT PEPTIDASES
FILE REFERENCE: H0824.70299US00
CURRENT APPLICATION NUMBER: US/16/641,630
CURRENT FILING DATE: 2020-02-24
PRIOR APPLICATION NUMBER: PCT/US2018/048134
PRIOR FILING DATE: 2018-08-27
PRIOR APPLICATION NUMBER: US 62/550,408
PRIOR FILING DATE: 2017-08-25
NUMBER OF SEQ ID NOS: 401
SEQ ID NO 294
LENGTH: 403
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic polypeptide
Pertinent Art
Chen and Barbieri (Multiple pocket recognition of SNAP25 by botulinum neurotoxin serotype E. J Biol Chem. 2007 Aug 31;282(35):25540-7, cited in the IDS) teaches that cleavage of SNAP-25 by BoNT/E LC depends on specific substrate recognition residues, including Leu166, Arg167, Asp127, Ala128, Ser129, and Ala130, which mediate substrate docking interactions (Abstract and Fig. 5). Chen further demonstrates that disruption of substrate interaction motifs eliminates cleavage activity (Fig. 3-4 and Table 1).
Allowable Subject Matter
Claim 8 is objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Conclusion
No claim is in condition for allowance.
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/NAGHMEH NINA MOAZZAMI/Examiner, Art Unit 1652
/RICHARD G HUTSON/Primary Examiner, Art Unit 1652