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 .
Election/Restrictions
1. Applicant's election on October 30, 2025 with traverse of Group I, claims 1, 2, 9, 11, 19, 24-29, and 31 is acknowledged.
Applicant elected the following species:
I) ACE2 extracellular domain polypeptide of the ACE2-Fc fusion polypeptide: a) an amino acid sequence having at least 90% identity to the amino acid sequence of any one of the residues 18-740 of SEQ ID NO: 60; the residues 18-708 of SEQ ID NO: 60; the residues 18-730 of SEQ ID NO: 60; and SEQ ID NOs: 1-4.
II) the Fc domain of the ACE2-Fc fusion polypeptide: a) comprises an amino acid sequence comprising at least one amino acid substitution relative to a wild-type Fc domain that decreases or eliminates binding of the Fc domain to a Fc receptor, optionally wherein the Fc receptor is a FcgIIa receptor.
III) A hinge region comprises an amino acid sequence of SEQ ID NO: 16.
IV) An ACE2-Fc fusion polypeptide comprising SEQ ID NO: 48.
V) A nucleic acid comprising SEQ ID NO: 50
VI) Coronavirus: h) the coronavirus descends from or is the 1) B.1.1.7 lineage, 11) B.1.351 lineage, iii) B.1.1.248 lineage, iv) B.1.617 lineage, v) B.1.617.2 lineage, or vi) B.1.617.3 lineage.
Applicant argues that the Examiner contends that Groups | and 2 lack unity of invention in view of Iwanaga et al. (https://doi.org/10.1101/2020.06.15.152157; hereinafter Iwanaga), in view of Strom et al. (WO 99/027711; hereinafter Strom). Applicant respectfully traverses the objection to the unity of invention. Applicant submits that Iwanaga does not qualify as prior art because it was posted on July 24, 2020 (see https://doi.org/10.1101/2020.06.15.152157, and the header of the pre-print (submitted herewith as Appendix A)), which is after the priority date (July 20, 2020) of the present application. Strom discloses fusion proteins with an immunoglobulin hinge region linker and does not teach or suggest an ACE2-Fc fusion polypeptide according to the pending claims. Accordingly, Strom does not anticipate or render obvious the pending claims.
Applicant’s arguments have been considered, but have not been found persuasive. The cited version of Iwanaga and submitted with the IDS of April 10, 2023 has a posting date of June 15, 2020, which is prior to the priority date of July 20, 2020. Thus, Iwanaga qualifies as prior art. An additional of copy Iwanaga with the posting date of June 15, 2020, is submitted herewith for convenience. Thus Applicant’s arguments are not found persuasive. For these reasons the restriction requirement is deemed to be proper and is therefore made FINAL.
2. Claims 1, 2, 9, 11, 19, 24-29, 31, 33, 35, and 37-39 are pending.
3. Claims 33, 35, and 37-39 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species or invention, there being no allowable generic or linking claim.
4. Claims 1, 2, 9, 11, 19, 24-29, and 31 are currently under consideration as drawn to the elected species.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
5. Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - This application contains sequence disclosures in accordance with the definitions for nucleotide and/or amino acid sequences set forth in 37 CFR 1.821(a)(1) and (a)(2). However, this application fails to comply with the requirements of 37 CFR 1.821 - 1.825.
The sequence disclosures are located at page 24 and page 87-line 6.
Required response – Applicant must provide:
A "Sequence Listing" part of the disclosure, as described above in item 1); as well as
An amendment specifically directing entry of the "Sequence Listing" part of the disclosure into the application in accordance with 1.825(b)(2);
A statement that the "Sequence Listing" includes no new matter in accordance with 1.825(b)(5); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(b)(4).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter;
If the "Sequence Listing" part of the disclosure is submitted according to item 1) b), c), or d) above, Applicant must also provide:
A replacement CRF in accordance with 1.825(b)(6); and
Statement according to item 2) a) or b) above.
Claim Objections
6. Claims 11 and 24 are objected to because of the following informalities: The references to Table 5 in claim 11 and Table 2, 3, or 4 in claim 24 are objected to because where possible, claims are to be complete in themselves. See MPEP 2173.05(s). 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.
7. Claims 1, 2, 9, 11, 19, 24, 25, 27, 29 and 31 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
The term “the Fc domain or fragment thereof has attenuated binding affinity for a Fcg receptor" in claim 1 is a relative term which renders claims 1 and its dependent claims indefinite. The term “the Fc domain or fragment thereof has attenuated binding affinity for a Fcg receptor " is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. The specification does not teach at what point the binding affinity for the Fc domain or fragment thereof for an a Fcg receptor or fragment thereof is considered to be attenuated or to what the binding affinity is being compared.
Section 2171 of the M.P.E.P. states
Two separate requirements are set forth in 35 U.S.C. 112(b) and pre-AIA 35 U.S.C. 112, second paragraph, namely that:
(A) the claims must set forth the subject matter that the inventor or a joint inventor regards as the invention; and
(B) the claims must particularly point out and distinctly define the metes and bounds of the subject matter to be protected by the patent grant.
The first requirement is a subjective one because it is dependent on what the inventor or a joint inventor for a patent regards as his or her invention. Note that although pre-AIA 35 U.S.C. 112, second paragraph, uses the phrase "which applicant regards as his invention," pre-AIA 37 CFR 1.41(a) provides that a patent is applied for in the name or names of the actual inventor or inventors.
The second requirement is an objective one because it is not dependent on the views of applicant or any particular individual, but is evaluated in the context of whether the claim is definite — i.e., whether the scope of the claim is clear to a hypothetical person possessing the ordinary level of skill in the pertinent art.
In the instant case of “the Fc domain or fragment thereof has attenuated binding affinity for a Fcg receptor", one of skill in the art could find representative examples in the art which have been defined in such terms, however, it is unclear at what point one of skill in the art would be infringing on the claims without limitations as to the metes and bounds of “the Fc domain or fragment thereof has attenuated binding affinity for a Fcg receptor" so that one of skill in the art would know at what point the binding affinity of the Fc domain or fragment thereof for an a Fcg receptor or fragment thereof is considered to be attenuated.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(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.
8. Claim(s) 1, 2, 9, 11, 19, 24-27, 29, and 31 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by US 2021/0363512 A1 (Reiter et al. Nov. 25, 2021, effectively filed May 22, 2020), “Reiter”.
Reiter teaches the present invention relates to fusion proteins of ACE2 with IgG Fc and the medical use of these fusion proteins, in particular in the prevention or treatment of infections with coronaviruses such as SARS-CoV-2. See abstract and ¶¶ 0012-0017.
Regarding claims 1, 2, 9, 11, and 24-26, Reiter teaches the ACE2-Fc fusion protein of SEQ ID NO: 9 which comprises amino acids 18 to 740 of human ACE2 (SEQ ID No. 3) with a H374N and a H378N mutation, the numbering referring to SEQ ID No. 1, the linking sequence according to SEQ ID No. 4 and the Fc portion of human IgG4 according to SEQ ID No. 5. See ¶ 0152.
Regarding claims 1, 2, 9, 11, and 24-26, Reiter teaches a H374N and a H378N mutation of ACE2 is inactivating. See ¶¶ 0024-0025.
Regarding claim 2, SEQ ID NO: 9 comprises an ACE2 region that is 99.7% identical to residues 18-740 of SEQ ID NO: 60. See Appendix.
Regarding claim 2, SEQ ID NO: 9 comprises an ACE2 region that is identical to SEQ ID NO: 1. See Appendix.
Regarding claim 26, SEQ ID NO: 9 is 99.5% identical to SEQ ID NO: 48. See Appendix.
Regarding claims 1, 2, 9, 11, and 24-26, the SEQ ID NO: 4 linker of SEQ ID NO: 9, ESKYGPPCPPCP, is identical to the claimed SEQ ID NO: 6 hinge from human IgG4. See Table 2 of the specification and Appendix. The SEQ ID NO: 4 linker comprises the S228P mutation. See ¶ 0148, Appendix and Table 2 of the specification. Although Reiter does not teach that the S228P mutation attenuates binding for an Fcg receptor, the instant specification teaches that the S228P mutation attenuates binding for an Fcg receptor. See p. 39-2nd paragraph of the instant specification. Thus, given that the Fc domain of Reiter contains the S228P mutation, it would have the same function of attenuating binding for an Fcg receptor.
Regarding claim 25, the SEQ ID NO: 4 linker contains a proline and a cysteine-proline dipeptide, which would be a hinge region as claimed. The use of "consists" in the body of the claims does not limit the open-ended "comprising" language in claim 1 from which claim 25 depends. See MPEP 2111.03 (II).
Regarding claims 1, 2, 9, 11, and 24-26, Reiter teaches the ACE2-IgG4-Fc fusion protein constructs 1 and 3 showed slightly lower affinity to FcγRI when compared to the IgG1 counterparts. The ACE2-IgG4-Fc of constructs 1 and 3 showed no binding to FcγRIIIa,. See ¶ 0275 and Table 3.
Reiter teaches SEQ ID NO: 9 is construct 4. See Table 1.
Regarding claim 9, Reiter teaches the ACE2-IgG4-Fc constructs (constructs 1-4) bind to the spike protein of SARS-CoV-2. See ¶¶ 0040, 0041 0267-0269 Table 2, Figs. 4A and B. Thus, the ACE2-IgG4-Fc constructs would bind SARS-CoV-2 virus.
Regarding claims 27, 29 and 31, Reiter teaches nucleic acid expression vectors and host cells, including mammalian cells, for expressing the ACE2 IgG Fc fusion proteins. See ¶¶ 0030, 0158-0163 and 0234.
Regarding claims 1, 2, 9, 11, 19, and 24-25, Reiter also teaches SEQ ID No. 12 (construct 7) which comprises amino acids 18 to 732 of human ACE2 (SEQ ID No. 2) with a H374N and a H378N mutation (inactivating mutations), the numbering referring to SEQ ID No. 1, the linking sequence according to SEQ ID No. 15 (DKTHTCPPCPA) and the Fc portion of human IgG1 according to SEQ ID No. 16. See ¶¶ 0155.
Regarding claim 19, SEQ ID No. 16 comprises the L234A and L235A substitutions in the Fc domain. See ¶¶ 0138, 0143 and 0144.
Regarding claims 24 and 25, SEQ ID No. 15 (DKTHTCPPCPA) comprises the claimed SEQ ID NOs: 21-25 and a proline or cysteine-proline dipeptide. See Table 3 of the instant specification.
Although Reiter does not teach that the L234A and L235A substitutions attenuate binding to an Fcg receptor, the instant specification teaches that the L234A and L235A substitutions attenuate binding to an Fcg receptor. See p. 39-2nd paragraph of the instant specification. Thus, given that the Fc domain of Reiter contains L234A and L235A substitutions, it would have the same function of attenuating binding to an Fcg receptor.
Regarding claim 9, Reiter teaches the ACE2-IgG1-Fc SEQ ID No. 12 (construct 7) binds to the spike protein of SARS-CoV-2. See ¶¶ 0040, 0041 0267-0269 Table 2, Figs. 4A and B. Thus, the ACE2-IgG1-Fc SEQ ID No. 12 construct would bind SARS-CoV-2 virus.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, 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.
9. Claim 28 is rejected under 35 U.S.C. 103 as being unpatentable over US 2021/0363512 A1 (Reiter et al. Nov. 25, 2021, effectively filed May 22, 2020), “Reiter” as applied to claims 1, 2, 9, 11, 19, 24-27, 29, and 31 above in further view of Sambrook et al. (Molecular Cloning A laboratory Manual, 2nd edition, Cold Spring Harbor, N.Y. 1989, pp. 16.3-36), “Sambrook”.
Reiter teaches as set forth above. SEQ ID NO: 9 is encoded by a sequence 99.5% identical to SEQ ID NO: 50. See Appendix.
Reiter teaches as set forth above, but does not teach a nucleic acid sequence having at least 90% identity to SEQ ID NO: 50.
Sambrook et al teach that cloned genes are conventionally expressed using expression vectors and that expression of cloned proteins have been used to: (1) confirm the identity of a cloned gene by using immunological or functional assays to detect the encoded protein; (2) produce large amounts of proteins of biological interest that are normally available in only limited quantities from natural sources; (3) to study the biosynthesis and intracellular transport of proteins following their expression in various cell types; and (4) to elucidate structure-function relationships by analyzing the properties of normal and mutant proteins (para bridging pages 16.3 and 16.4).
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Reiter and Sambrook to isolate the nucleic acid encoding the ACE2-Fc fusion proteins of Reiter, like SEQ ID NO: 9, to clone into an expression vector as taught by Sambrook because Sambrook specifically teaches that expressed cloned proteins are used to: (1) confirm the identity of a cloned gene by using immunological or functional assays to detect the encoded protein; (2) produce large amounts of proteins of biological interest that are normally available in only limited quantities from natural sources; (3) to study the biosynthesis and intracellular transport of proteins following their expression in various cell types; and (4) to elucidate structure-function relationships by analyzing the properties of normal and mutant proteins. Thus, one would have been motivated to isolate the nucleic acid encoding the ACE2-Fc fusion proteins of Reiter, like SEQ ID NO: 9, for the characterization and use as taught by Sambrook.
Additionally, it is noted that the courts have found that the disclosure of the polypeptide makes the nucleic acid encoding the protein obvious as the methods of obtaining the nucleic acids are routine in the art and can be obtained with a reasonable expectation of success. See MPEP 2143(E)(Example 3), Ex parte Kubin, 83 USPQ2d 1410 (Bd. Pat. App. & Int. 2007), and In re Kubin 90 USPQ2d 1417 (U. S. Court of Appeals Fed. Cir. 2009).
10. Claim 24 is alternatively rejected under 35 U.S.C. 103 as being unpatentable over US 2021/0363512 A1 (Reiter et al. Nov. 25, 2021, effectively filed May 22, 2020), “Reiter” as applied to claims 1, 2, 9, 11, 19, 24-27, 29, and 31 above in further view of WO 99/02711 (Strom et al. Jan. 21, 1999, of record) and US 2004/0102369 A1 (Wu et al. May 27, 2004), “Wu”.
Reiter teaches as set forth above, but does not teach using the elected hinge region of SEQ ID NO: 16 (EPKSCDKTHTCP).
Strom teaches making fusion protein with IgG hinge linker regions. See abstract, Table-p. 8 and claims. Strom teaches that the IgG hinge regions are flexible and allow the binding regions to move freely. See p. 6-3rd paragraph. Strom teaches that the hinge can be added to either terminus of a protein allowing freedom of interaction with ligand. See p. 2-3rd paragraph.
Wu teaches using EPKSCDKTHTCP (SEQ ID NO: 2) as a hinge in a fusion protein of FGF-2 and an antibody to human insulin receptor HIRMAb for administration to patients. See ¶¶ 0023 and 0087 and Fig. 8.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Reiter, Strom and Wu and use an IgG hinge, like the EPKSCDKTHTCP IgG1 hinge of Wu, in the ACE2-human IgG1 fusion protein of Reiter because Reiter teaches using the DKTHTCPPCPA hinge, which is part of the IgG1 hinge as taught by Strom in Table 1 and Wu, to provide flexibility of movement and interaction ACE2 with coronavirus. One would have been motivated to use the EPKSCDKTHTCP IgG1 hinge in the in the ACE2-human IgG1 fusion protein of Reiter because Wu teaches the successful use of the hinge in a fusion construct and to provide flexibility of movement and interaction ACE2 with coronavirus. .
Conclusion
11. No claims allowed.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached M-F 8:30-5:30 Eastern Time.
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, Janet L Epps-Smith can be reached at 571-272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/PETER J REDDIG/Primary Examiner, Art Unit 1646
APPENDIX
Alignment of SEQ ID NO: 60 with SEQ ID NO: 9 of Reiter
Title: US-18-016-209-60
Perfect score: 4291
Sequence: 1 MSSSSWLLLSLVAVTAAQST..........ISKGENNPGFQNTDDVQTSF 805
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 952 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-17-327-081-9.pep:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 3868 90.1 952 1 US-17-327-081-9 ACE2 fusion protei
ALIGNMENTS
RESULT 1
US-17-327-081-9
Query Match 90.1%; Score 3868; DB 1; Length 952;
Best Local Similarity 99.7%;
Matches 721; Conservative 2; Mismatches 0; Indels 0; Gaps 0;
Qy 18 QSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQS 77
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQS 60
Qy 78 TLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDN 137
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDN 120
Qy 138 PQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYE 197
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYE 180
Qy 198 DYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYIS 257
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYIS 240
Qy 258 PIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVS 317
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVS 300
Qy 318 VGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHHEMG 377
||||||||||||||||||||||||||||||||||||||||||||||||||||||||:|||
Db 301 VGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHNEMG 360
Qy 378 HIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEIN 437
:|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEIN 420
Qy 438 FLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETY 497
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 FLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETY 480
Qy 498 CDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNM 557
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNM 540
Qy 558 LRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQS 617
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQS 600
Qy 618 IKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKP 677
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 IKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKP 660
Qy 678 RISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQP 737
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 RISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQP 720
Qy 738 PVS 740
|||
Db 721 PVS 723
Alignment of SEQ ID NO: 1 with SEQ ID NO: 9 of Reiter
Title: US-18-016-209-1
Perfect score: 3878
Sequence: 1 QSTIEEQAKTFLDKFNHEAE..........SLEFLGIQPTLGPPNQPPVS 723
Scoring table: BLOSUM62
Gapop 10.0 , Gapext 0.5
Searched: 1 seqs, 952 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-17-327-081-9.pep:*
SUMMARIES
%
Result Query
No. Score Match Length DB ID Description
----------------------------------------------------------------------------
1 3878 100.0 952 1 US-17-327-081-9 ACE2 fusion protei
ALIGNMENTS
RESULT 1
US-17-327-081-9
Query Match 100.0%; Score 3878; DB 1; Length 952;
Best Local Similarity 100.0%;
Matches 723; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQS 60
Qy 61 TLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDN 120
Qy 121 PQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYE 180
Qy 181 DYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYIS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYIS 240
Qy 241 PIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVS 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVS 300
Qy 301 VGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHNEMG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 VGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHNEMG 360
Qy 361 NIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEIN 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEIN 420
Qy 421 FLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETY 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 FLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETY 480
Qy 481 CDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNM 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNM 540
Qy 541 LRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQS 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQS 600
Qy 601 IKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKP 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 IKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKP 660
Qy 661 RISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQP 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 RISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQP 720
Qy 721 PVS 723
|||
Db 721 PVS 723
Alignment of SEQ ID NO: 48 with SEQ ID NO: 9 of Reiter
Sequence 9, US/17327081
Publication No. US20210363512A1
GENERAL INFORMATION
APPLICANT: Formycon AG
TITLE OF INVENTION: ACE2 fusion proteins and uses thereof
FILE REFERENCE: F09553WO
CURRENT APPLICATION NUMBER: US/17/327,081
CURRENT FILING DATE: 2021-05-21
PRIOR APPLICATION NUMBER: EP20176139.2
PRIOR FILING DATE: 2020-05-22
PRIOR APPLICATION NUMBER: EP20204774.2
PRIOR FILING DATE: 2020-10-29
PRIOR APPLICATION NUMBER: EP20210297.6
PRIOR FILING DATE: 2020-11-27
PRIOR APPLICATION NUMBER: EP21164684.9
PRIOR FILING DATE: 2021-03-24
PRIOR APPLICATION NUMBER: EP21170519.9
PRIOR FILING DATE: 2021-04-26
NUMBER OF SEQ ID NOS: 18
SEQ ID NO 9
LENGTH: 952
TYPE: PRT
ORGANISM: artificial
FEATURE:
OTHER INFORMATION: fusion protein 4
Query Match 99.6%; Score 5077; Length 952;
Best Local Similarity 99.5%;
Matches 947; Conservative 0; Mismatches 1; Indels 4; Gaps 1;
Qy 1 QSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QSTIEEQAKTFLDKFNHEAEDLFYQSSLASWNYNTNITEENVQNMNNAGDKWSAFLKEQS 60
Qy 61 TLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDN 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TLAQMYPLQEIQNLTVKLQLQALQQNGSSVLSEDKSKRLNTILNTMSTIYSTGKVCNPDN 120
Qy 121 PQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYE 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PQECLLLEPGLNEIMANSLDYNERLWAWESWRSEVGKQLRPLYEEYVVLKNEMARANHYE 180
Qy 181 DYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYIS 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 DYGDYWRGDYEVNGVDGYDYSRGQLIEDVEHTFEEIKPLYEHLHAYVRAKLMNAYPSYIS 240
Qy 241 PIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVS 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PIGCLPAHLLGDMWGRFWTNLYSLTVPFGQKPNIDVTDAMVDQAWDAQRIFKEAEKFFVS 300
Qy 301 VGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHNEMG 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 VGLPNMTQGFWENSMLTDPGNVQKAVCHPTAWDLGKGDFRILMCTKVTMDDFLTAHNEMG 360
Qy 361 NIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEIN 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 NIQYDMAYAAQPFLLRNGANEGFHEAVGEIMSLSAATPKHLKSIGLLSPDFQEDNETEIN 420
Qy 421 FLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETY 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 FLLKQALTIVGTLPFTYMLEKWRWMVFKGEIPKDQWMKKWWEMKREIVGVVEPVPHDETY 480
Qy 481 CDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNM 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CDPASLFHVSNDYSFIRYYTRTLYQFQFQEALCQAAKHEGPLHKCDISNSTEAGQKLFNM 540
Qy 541 LRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQS 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LRLGKSEPWTLALENVVGAKNMNVRPLLNYFEPLFTWLKDQNKNSFVGWSTDWSPYADQS 600
Qy 601 IKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKP 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 IKVRISLKSALGDKAYEWNDNEMYLFRSSVAYAMRQYFLKVKNQMILFGEEDVRVANLKP 660
Qy 661 RISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQP 720
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 RISFNFFVTAPKNVSDIIPRTEVEKAIRMSRSRINDAFRLNDNSLEFLGIQPTLGPPNQP 720
Qy 721 PVS----GPPCPPCPAPEFEGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQF 776
||| |||||||||||| ||||||||||||||||||||||||||||||||||||||||
Db 721 PVSESKYGPPCPPCPAPEFLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQF 780
Qy 777 NWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKT 836
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 NWYVDGVEVHNAKTKPREEQFNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKT 840
Qy 837 ISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP 896
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 ISKAKGQPREPQVYTLPPSQEEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTP 900
Qy 897 PVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 948
||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 PVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSVMHEALHNHYTQKSLSLSLGK 952
Alignment of SEQ ID NO: 50 with SEQ ID NO: 9 of Reiter
US-17-327-081-9
(NOTE: this sequence has 3 duplicates in the database searched.
See complete list at the end of this report)
Sequence 9, US/17327081
Publication No. US20210363512A1
GENERAL INFORMATION
APPLICANT: Formycon AG
TITLE OF INVENTION: ACE2 fusion proteins and uses thereof
FILE REFERENCE: F09553WO
CURRENT APPLICATION NUMBER: US/17/327,081
CURRENT FILING DATE: 2021-05-21
PRIOR APPLICATION NUMBER: EP20176139.2
PRIOR FILING DATE: 2020-05-22
PRIOR APPLICATION NUMBER: EP20204774.2
PRIOR FILING DATE: 2020-10-29
PRIOR APPLICATION NUMBER: EP20210297.6
PRIOR FILING DATE: 2020-11-27
PRIOR APPLICATION NUMBER: EP21164684.9
PRIOR FILING DATE: 2021-03-24
PRIOR APPLICATION NUMBER: EP21170519.9
PRIOR FILING DATE: 2021-04-26
NUMBER OF SEQ ID NOS: 18
SEQ ID NO 9
LENGTH: 952
TYPE: PRT
ORGANISM: artificial
FEATURE:
OTHER INFORMATION: fusion protein 4
Alignment Scores:
Length: 952
Score: 5077.00 Matches: 947
Percent Similarity: 99.5% Conservative: 0
Best Local Similarity: 99.5% Mismatches: 1
Query Match: 95.4% Indels: 4
Gaps: 1
US-18-016-209-50 (1-2904) x US-17-327-081-9 (1-952)
Qy 58 CAGTCAACAATCGAGGAGCAGGCAAAGACCTTCCTGGACAAGTTTAACCACGAAGCGGAG 117
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GlnSerThrIleGluGluGlnAlaLysThrPheLeuAspLysPheAsnHisGluAlaGlu 20
Qy 118 GACCTGTTCTACCAGAGCAGCCTGGCGAGCTGGAATTACAACACCAACATCACCGAGGAG 177
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 AspLeuPheTyrGlnSerSerLeuAlaSerTrpAsnTyrAsnThrAsnIleThrGluGlu 40
Qy 178 AACGTGCAGAACATGAATAACGCTGGCGACAAGTGGAGCGCCTTCTTGAAGGAGCAATCC 237
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 41 AsnValGlnAsnMetAsnAsnAlaGlyAspLysTrpSerAlaPheLeuLysGluGlnSer 60
Qy 238 ACCCTGGCCCAGATGTACCCGCTGCAAGAGATACAGAACCTGACTGTGAAGCTGCAACTG 297
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ThrLeuAlaGlnMetTyrProLeuGlnGluIleGlnAsnLeuThrValLysLeuGlnLeu 80
Qy 298 CAGGCCCTGCAGCAGAACGGCTCCAGCGTGCTGAGCGAAGACAAGAGCAAAAGGCTGAAT 357
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 GlnAlaLeuGlnGlnAsnGlySerSerValLeuSerGluAspLysSerLysArgLeuAsn 100
Qy 358 ACCATATTGAACACGATGAGCACCATCTACAGCACCGGCAAAGTATGCAACCCCGACAAC 417
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 101 ThrIleLeuAsnThrMetSerThrIleTyrSerThrGlyLysValCysAsnProAspAsn 120
Qy 418 CCCCAAGAGTGTCTGTTGTTGGAACCCGGCCTGAACGAGATTATGGCGAACTCCCTGGAC 477
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ProGlnGluCysLeuLeuLeuGluProGlyLeuAsnGluIleMetAlaAsnSerLeuAsp 140
Qy 478 TACAACGAACGCCTGTGGGCATGGGAGTCTTGGAGGTCAGAGGTTGGCAAGCAACTGAGG 537
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 TyrAsnGluArgLeuTrpAlaTrpGluSerTrpArgSerGluValGlyLysGlnLeuArg 160
Qy 538 CCGTTGTACGAAGAGTACGTGGTGCTGAAGAACGAAATGGCACGGGCCAATCATTATGAG 597
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 161 ProLeuTyrGluGluTyrValValLeuLysAsnGluMetAlaArgAlaAsnHisTyrGlu 180
Qy 598 GACTACGGTGATTATTGGAGGGGCGACTACGAGGTGAACGGCGTGGACGGCTACGACTAT 657
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 AspTyrGlyAspTyrTrpArgGlyAspTyrGluValAsnGlyValAspGlyTyrAspTyr 200
Qy 658 AGCAGGGGCCAACTTATAGAGGACGTAGAGCACACTTTTGAGGAAATCAAACCCCTGTAC 717
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 201 SerArgGlyGlnLeuIleGluAspValGluHisThrPheGluGluIleLysProLeuTyr 220
Qy 718 GAGCACTTGCATGCCTACGTACGCGCCAAACTGATGAATGCGTACCCCAGCTACATCAGC 777
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 221 GluHisLeuHisAlaTyrValArgAlaLysLeuMetAsnAlaTyrProSerTyrIleSer 240
Qy 778 CCCATCGGCTGCCTGCCCGCACACCTGCTCGGCGACATGTGGGGCCGATTCTGGACCAAT 837
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 ProIleGlyCysLeuProAlaHisLeuLeuGlyAspMetTrpGlyArgPheTrpThrAsn 260
Qy 838 CTGTATAGCCTCACCGTGCCCTTTGGCCAGAAGCCGAACATAGATGTGACGGATGCTATG 897
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 261 LeuTyrSerLeuThrValProPheGlyGlnLysProAsnIleAspValThrAspAlaMet 280
Qy 898 GTAGACCAGGCGTGGGATGCACAGCGCATCTTCAAGGAGGCCGAGAAGTTCTTCGTGAGC 957
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 281 ValAspGlnAlaTrpAspAlaGlnArgIlePheLysGluAlaGluLysPhePheValSer 300
Qy 958 GTCGGCTTGCCCAACATGACCCAGGGTTTCTGGGAGAACTCAATGCTGACTGACCCCGGC 1017
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 ValGlyLeuProAsnMetThrGlnGlyPheTrpGluAsnSerMetLeuThrAspProGly 320
Qy 1018 AACGTACAGAAAGCCGTATGCCACCCAACTGCTTGGGACCTGGGTAAGGGAGACTTCCGG 1077
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 321 AsnValGlnLysAlaValCysHisProThrAlaTrpAspLeuGlyLysGlyAspPheArg 340
Qy 1078 ATCCTCATGTGTACCAAGGTGACCATGGATGACTTTCTCACCGCCCACAATGAAATGGGC 1137
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 341 IleLeuMetCysThrLysValThrMetAspAspPheLeuThrAlaHisAsnGluMetGly 360
Qy 1138 AACATCCAGTACGATATGGCCTACGCAGCGCAGCCATTCCTTCTGAGGAACGGTGCCAAC 1197
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 AsnIleGlnTyrAspMetAlaTyrAlaAlaGlnProPheLeuLeuArgAsnGlyAlaAsn 380
Qy 1198 GAGGGCTTCCATGAGGCAGTCGGAGAGATCATGAGCCTGTCAGCGGCGACCCCTAAACAT 1257
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 381 GluGlyPheHisGluAlaValGlyGluIleMetSerLeuSerAlaAlaThrProLysHis 400
Qy 1258 CTGAAGAGCATCGGGCTGCTGTCTCCGGACTTTCAAGAGGACAATGAGACTGAGATCAAC 1317
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 401 LeuLysSerIleGlyLeuLeuSerProAspPheGlnGluAspAsnGluThrGluIleAsn 420
Qy 1318 TTCCTCCTGAAACAGGCGCTGACCATTGTAGGCACCTTGCCCTTCACCTACATGCTGGAG 1377
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 PheLeuLeuLysGlnAlaLeuThrIleValGlyThrLeuProPheThrTyrMetLeuGlu 440
Qy 1378 AAGTGGCGATGGATGGTGTTTAAGGGCGAGATCCCGAAGGACCAGTGGATGAAAAAGTGG 1437
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 441 LysTrpArgTrpMetValPheLysGlyGluIleProLysAspGlnTrpMetLysLysTrp 460
Qy 1438 TGGGAGATGAAGAGGGAGATCGTCGGCGTAGTTGAGCCGGTCCCCCACGACGAAACCTAC 1497
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 461 TrpGluMetLysArgGluIleValGlyValValGluProValProHisAspGluThrTyr 480
Qy 1498 TGCGATCCTGCCAGCCTGTTCCACGTGAGCAACGATTACAGTTTTATCAGGTACTACACC 1557
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 CysAspProAlaSerLeuPheHisValSerAsnAspTyrSerPheIleArgTyrTyrThr 500
Qy 1558 AGGACCCTTTACCAATTTCAGTTCCAGGAGGCACTGTGCCAGGCCGCCAAGCACGAAGGC 1617
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 501 ArgThrLeuTyrGlnPheGlnPheGlnGluAlaLeuCysGlnAlaAlaLysHisGluGly 520
Qy 1618 CCCCTGCACAAGTGCGACATCAGCAACAGCACCGAGGCGGGTCAAAAGCTGTTTAACATG 1677
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 521 ProLeuHisLysCysAspIleSerAsnSerThrGluAlaGlyGlnLysLeuPheAsnMet 540
Qy 1678 CTGAGGCTGGGCAAGAGCGAGCCGTGGACCCTGGCCCTGGAAAACGTTGTGGGCGCAAAA 1737
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 LeuArgLeuGlyLysSerGluProTrpThrLeuAlaLeuGluAsnValValGlyAlaLys 560
Qy 1738 AACATGAACGTGAGGCCCCTGCTGAACTACTTCGAGCCCCTGTTCACCTGGCTGAAGGAC 1797
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 561 AsnMetAsnValArgProLeuLeuAsnTyrPheGluProLeuPheThrTrpLeuLysAsp 580
Qy 1798 CAGAACAAGAACAGTTTCGTGGGCTGGAGTACCGATTGGAGTCCCTATGCCGACCAGAGC 1857
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 581 GlnAsnLysAsnSerPheValGlyTrpSerThrAspTrpSerProTyrAlaAspGlnSer 600
Qy 1858 ATCAAGGTGAGGATTAGCCTCAAGAGCGCCCTGGGCGACAAGGCCTATGAATGGAACGAC 1917
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 IleLysValArgIleSerLeuLysSerAlaLeuGlyAspLysAlaTyrGluTrpAsnAsp 620
Qy 1918 AACGAGATGTACCTGTTCAGGTCAAGCGTGGCCTACGCCATGAGGCAGTACTTCCTGAAA 1977
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 621 AsnGluMetTyrLeuPheArgSerSerValAlaTyrAlaMetArgGlnTyrPheLeuLys 640
Qy 1978 GTGAAGAACCAGATGATACTGTTCGGCGAGGAGGACGTGAGGGTGGCCAACCTGAAGCCC 2037
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 641 ValLysAsnGlnMetIleLeuPheGlyGluGluAspValArgValAlaAsnLeuLysPro 660
Qy 2038 AGGATATCATTCAATTTCTTCGTGACCGCTCCCAAGAACGTGAGCGACATCATCCCCAGG 2097
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 ArgIleSerPheAsnPhePheValThrAlaProLysAsnValSerAspIleIleProArg 680
Qy 2098 ACCGAGGTGGAGAAGGCCATCAGGATGAGCCGCAGCAGGATTAACGACGCCTTCAGGCTG 2157
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 681 ThrGluValGluLysAlaIleArgMetSerArgSerArgIleAsnAspAlaPheArgLeu 700
Qy 2158 AACGATAACAGCCTGGAGTTCCTTGGCATCCAGCCAACCCTGGGACCACCCAACCAGCCT 2217
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 701 AsnAspAsnSerLeuGluPheLeuGlyIleGlnProThrLeuGlyProProAsnGlnPro 720
Qy 2218 CCCGTTAGC------------GGACCCCCCTGTCCTCCTTGCCCTGCTCCTGAATTTGAG 2265
||||||||| ||||||||||||||||||||||||||||||||||||
Db 721 ProValSerGluSerLysTyrGlyProProCysProProCysProAlaProGluPheLeu 740
Qy 2266 GGAGGCCCCTCCGTCTTCCTGTTTCCCCCCAAGCCCAAGGACACCCTGATGATCTCCCGG 2325
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 741 GlyGlyProSerValPheLeuPheProProLysProLysAspThrLeuMetIleSerArg 760
Qy 2326 ACACCCGAAGTCACCTGCGTCGTGGTGGATGTCAGCCAGGAAGATCCCGAGGTGCAGTTC 2385
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 761 ThrProGluValThrCysValValValAspValSerGlnGluAspProGluValGlnPhe 780
Qy 2386 AACTGGTACGTGGACGGAGTGGAGGTGCATAACGCCAAAACCAAGCCCAGGGAAGAGCAG 2445
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 781 AsnTrpTyrValAspGlyValGluValHisAsnAlaLysThrLysProArgGluGluGln 800
Qy 2446 TTCAACAGCACCTATCGGGTCGTGTCCGTGCTCACCGTCCTGCATCAGGATTGGCTCAAC 2505
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 801 PheAsnSerThrTyrArgValValSerValLeuThrValLeuHisGlnAspTrpLeuAsn 820
Qy 2506 GGCAAGGAGTACAAGTGCAAGGTGTCCAACAAGGGCCTGCCCTCCTCCATCGAGAAGACC 2565
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 821 GlyLysGluTyrLysCysLysValSerAsnLysGlyLeuProSerSerIleGluLysThr 840
Qy 2566 ATCTCCAAGGCTAAGGGCCAACCTCGGGAGCCCCAAGTGTATACCCTCCCTCCCAGCCAG 2625
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 841 IleSerLysAlaLysGlyGlnProArgGluProGlnValTyrThrLeuProProSerGln 860
Qy 2626 GAGGAGATGACCAAGAATCAAGTGAGCCTGACCTGCCTCGTGAAGGGATTTTACCCCTCC 2685
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 861 GluGluMetThrLysAsnGlnValSerLeuThrCysLeuValLysGlyPheTyrProSer 880
Qy 2686 GACATCGCTGTGGAATGGGAAAGCAATGGCCAACCTGAGAACAACTACAAGACCACACCC 2745
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 881 AspIleAlaValGluTrpGluSerAsnGlyGlnProGluAsnAsnTyrLysThrThrPro 900
Qy 2746 CCCGTGCTGGACTCCGATGGCTCCTTCTTCCTGTACAGCAGGCTGACCGTGGACAAATCC 2805
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 901 ProValLeuAspSerAspGlySerPhePheLeuTyrSerArgLeuThrValAspLysSer 920
Qy 2806 CGGTGGCAAGAGGGAAACGTGTTCAGCTGCTCCGTGATGCACGAGGCTCTCCACAACCAC 2865
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 921 ArgTrpGlnGluGlyAsnValPheSerCysSerValMetHisGluAlaLeuHisAsnHis 940
Qy 2866 TACACCCAGAAGAGCCTCTCCCTGAGCCTCGGCAAG 2901
||||||||||||||||||||||||||||||||||||
Db 941 TyrThrGlnLysSerLeuSerLeuSerLeuGlyLys 952