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 the Claims
Claims 1 – 36 are currently pending and are the subject of this Office Action. This is the first Office Action on the merits of the claims.
Information Disclosure Statement
No information disclosure statement has been filed in this case. The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
Drawings
The drawings are objected to because FIGs. 1 and 2 include text that are illegible and must be modified so that they are clear.
The x-axis coordinates of each of FIGs. 1 and 2 are blurry and difficult to read.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 112
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, 2, 4 – 6, 11 – 16, 23 – 31, and 33 – 36 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.
The following quotation from section 2163 of the Manual of Patent Examination Procedure (MPEP) is a brief discussion of what is required in a specification to satisfy the 35 U.S.C. 112 written description requirements for a generic claim covering several distinct inventions:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice... reduction to drawings...or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus... See BU Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the specification must provide written description support for the entire scope of the genus. Support for a genus is generally found where the applicant has provided a number of examples sufficient so that one in the art would recognize from the specification the scope of what is being claimed.
Claims 1, 2, 4 – 6, 11 – 16, 23 – 31, and 33 – 36 are rejected as lacking adequate descriptive support for a possession of an anti-idiotype antibody or antigen binding portion thereof that specifically binds a target antibody that comprises CD9B441.
The composition requires the genus of any generic anti-idiotype antibody or antigen binding portion thereof that specifically binds a target antibody that comprises CD9B441, but does not provide a representative number of examples of such antibodies. The specification presents anti-Idiotypic antibodies A003B192 and A003B274 (Example 3, p. 36) which do not cover the genus of antibodies that may possibly bind a target antibody that comprises CD9B441. Thus, the application fails to provide examples of species within the claimed genus.
Regarding claims 4 and 5, the specification does not describe an anti-idiotype antibody or antigen-binding portion of claim 1, wherein the VL domain has an amino acid sequence having at least 90% sequence identity to SEQ ID NO: 8 or 9 that binds CD9B441 without a VH domain.
Regarding claim 6, multiple variations of HFW2, HFW4, HCDR1, HCDR2, HCDR3 result in a variety of structures for the anti-idiotype antibody or antigen-binding that is not supported by the present specification.
The decision of Amgen v. Sanofi, 872, F.3d 1367 (Fed. Cir. 2017) supports expanded analysis of whether a claim drawn to an antibody being specific for an epitope, even a specific epitope, permits an applicant to pursue all possible antibodies that are capable of being produced against such an epitope. Presently, the claimed antibody composition used is only defined by functional properties but no specific structure is recited by the claims. For example, according to the specification, “’[a]nti-idiotype antibody’ or ‘anti-idiotypic antibody’ refers to an antibody that specifically binds to the variable region of another antibody. In the case of A003B192 and A003B274, an anti-idiotype antibody specifically binds an anti-CD79b antibody”(p. 9, lines 5 – 7), and thus, the anti-idiotype antibody of claim 1 can bind any epitope on the variable region of a target antibody that comprises CD9B441 and is not defined by a specific structure. In view of the fact patterns detailed in Amgen v. Sanofi, applicants are not in possession of such an antibody which can bind to any epitope presented by the claimed polypeptides in claims 1, 2, 4 – 6, 11 – 16, 23 – 31, and 33 – 36.
Providing SEQ ID NOs defining the specific sequences of the anti-idiotype antibodies or antibody fragments for claims 1, 2, 4 – 6, 11 – 16, 23 – 31, and 33 – 36 can provide sufficient structures.
In view of this uncertainty and the lack of a representative number of examples of the claimed genus, the claims are rejected for lack of adequate written description support.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 4 – 5 and 34 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.
Claim 4 recites the limitation "VL". There is insufficient antecedent basis for this limitation in the claim with respect to claim 1.
Claim 5 recites the limitation "light chain". There is insufficient antecedent basis for this limitation in the claim with respect to claim 1 or 3.
Claim 34 is indefinite because it is not clear if the claim is drawn to a product, a method, or both. See MPEP 2173 (p)(II).
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, 2, 11 – 16, 23 – 30, and 32 – 36 are rejected under 35 U.S.C. 103 as being unpatentable over LOBB (WO 2018/156802 A1, published 08/30/2018; see PTO-892) in view of GANESAN (US 2021/145878 A1, filed 11/17/2020; see PTO-892).
The present application is directed to an anti-idiotype antibody or antigen binding portion thereof that specifically binds a target antibody that comprises CD9B441.
According to the present specification, “[t]he term ‘CD9B441’ refers to any antibody, antigen-binding portion thereof, or any other protein that contains variable regions derived from CD9B441 VL (SEQ ID NO: 29) and CD9B441 VH (SEQ ID NO: 30), including a CAR. In certain embodiments, an anti-idiotype antibody of the disclosure specifically binds a protein comprising a VL domain as set forth in SEQ ID NO: 29 and/or a VH domain as set forth in SEQ ID NO: 30. In certain embodiments, an anti-idiotype antibody of the disclosure specifically binds a protein comprising the 3 CDRs of the VL domain set forth in SEQ ID NO: 29 and the 3 CDRs of the VH domain set forth in SEQ ID NO: 30” (p. 19, lines 4 – 11 of the specification). Thus, the limitations of present claim 2 defines the target antibody comprising CD9B441.
LOBB is directed to cell comprising a constitutive expression construct encoding a fusion protein comprising (a) an antigen-binding protein or fragment that binds a tumor antigen; and (b) an anti-idiotype antibody or fragment, or an anti-idiotype peptide, that binds an antigen binding domain of a cellular therapeutic, antibody, or antibody-drug conjugate. See claim 1. LOBB discloses that the anti-idiotype antibody or fragment, or the anti-idiotype peptide, binds an anti-CD19, anti-CD20, anti-CD21, anti-CD22, anti-CD24, anti-CD79a, anti-CD79b. See claim 19. Thus, so like POLSON, LOBB teaches the an anti-idiotype antibody targeting an anti-CD79b antibody to treat cancer such as lymphoma (see paragraph 0113.
GANESAN is directed to CD79b-targeting chimeric antigen receptors (CARs) comprising CD79b-targeting single-chain variable fragments for the treatment of cancer, such as Non-Hodgkin lymphoma (NHL). See paragraphs 0003 and 0005. GANESAN discloses the sequences of SEQ ID NOs: 29 and 30 that define CD9B441. GANESAN’s SEQ ID NO: 32 is identical to present SEQ ID NO: 29 of present claim 2. GANESAN’s SEQ ID NO: 14 is identical to present SEQ ID NO: 30 of present claim 2. See Appendix.
Regarding claims 1 and 2, because LOBB teaches an anti-idiotype antibody directed at an anti-CD79b antibody for the treatment of cancer and GANESAN teaches the CD79b-targeting sequences of present SEQ ID NOs: 29 and 30 (CD9B441), it would have been obvious to one having ordinary skill in the art to produce s an anti-CD79b anti-idiotype antibody of LOBB to target GANESAN’s anti-CD79b sequences to detect anti-CD79b CAR of GANESAN or bring additional therapeutics to the cancer cell by targeting CAR binding domain (see paragraphs 0223-0224 of LOBB).
Regarding claim 11, LOBB discloses that an antigen binding domain includes an antibody or antigen-binding fragment described herein (e.g., a Fab fragment, Fab’ fragment, F(ab’)2 fragment, scFv fragment). See paragraph 0108.
Regarding claim 12, LOBB discloses that the antibody is monoclonal. See paragraph 0106.
Regarding claims 13 and 15, LOBB discloses that the antibody sequence elements are fully human, or are humanized, primatized, chimeric, etc, as is known in the art. See paragraph 0106.
Regarding claim 14, LOBB discloses that the sequence of the leader and constant domains were obtained from a murine IgG2a antibody. See paragraph 0469.
Regarding claim 16, LOBB discloses expression construct encoding a fusion protein comprising (a) an antigen-binding protein or fragment that binds a tumor antigen; and (b) an anti-idiotype antibody or fragment. See claim 1.
Regarding claims 23, 26 – 29, LOBB teaches that anti-idiotype antibodies are known in the art, and have been used to detect a VH/VL pair, or scFv, e.g., as displayed on the surface of a CAR T cell (see paragraph 0226). It would have been obvious to one having ordinary skill in the art to modify LOBB’s method in order to detect CD9B441, and because T cells are found in blood, it would have been obvious that the biological sample is blood.
Regarding claim 24 and 25, LOBB teaches that the antibody may contain a covalent modification (e.g., attachment of a glycan, a payload (e.g., a detectable moiety). See paragraph 0106, last sentence. Because the detectable label is covalently attached, it is likely added before using the antibody is used in a method of detecting.
Regarding claim 30, according to the present specification, CD9B441 is an anti-CD79b antibody (p. 2, last sentence). Because LOBB teaches anti-idiotype antibodies directed at anti-CD79b antibodies as discussed above and GANESAN discloses anti-CD79b sequences, it would have been obvious to modify LOBB’s anti-CD79b antibody with GANESAN’s anti-CD79b sequences.
Regarding claim 32, GANESAN discloses SEQ ID NO: 31. GANESAN’s SEQ ID NO: 180 discloses present SEQ ID NO: 31 with 100% identity. See Appendix.
Regarding claim 33 – 34 , GANESAN teaches a kit for detecting CD79b. See paragraphs 0538 – 0540. Because LOBB teaches an anti-idiotype antibody directed at an anti-CD79b antibody, and GANESAN teaches the sequences of the anti-CD79b that may be used in a kit for detecting, it would have been obvious to one having ordinary skill in the art to modify GANESAN’s kit with LOBB’s anti-idiotype antibody.
Regarding claim 35, LOBB teaches that the disclosed proteins may be purified by any method known in the art for purification, for example, by chromatography (e.g., ion exchange, affinity, and sizing column chromatography), centrifugation, differential solubility, or by any other standard technique for purification of proteins. For example, an antibody can be isolated and purified by appropriately selecting and combining affinity columns such as Protein A column with chromatography columns, filtration, ultra filtration, salting-out and dialysis procedures (see Antibodies: A Laboratory Manual, Ed Harlow, David Lane, Cold Spring Harbor Laboratory, 1988). LOBB also teaches that a polypeptide can be purified from natural sources (see paragraph 0329) suggesting purifying proteins like CD9B441 from a biological sample. Thus, because Protein A binds to the antibody to be purified, it would have been obvious to one having ordinary skill in the art to use an antibody specific to CD9B441 to purify CD9B441 in a method of purification as known in the art and as LOBB teaches.
Regarding claim 36, LOBB teaches that anti-idiotype antibodies are known in the art, and have been used to detect a VH/VL pair, or scFv, e.g., as displayed on the surface of a CAR T cell (see paragraph 0226). Thus, it would have been obvious to one having ordinary skill in the art to use the teachings of LOBB to select CAR-T cells.
Claims 1, 4 – 5, 11-13 and 15 – 22 are rejected under 35 U.S.C. 103 as being unpatentable in over of AMANN (WO 2016/075278 A1, published 05/19/2016; see PTO-892).
AMANN is directed to TNF family ligand trimer-containing antigen binding molecules for use in the treatment of cancer, such as non-Hodgkin B cell lymphoma. See abstract and p. 55, lines 3 – 21. AMANN discloses the sequences of SEQ ID NOs: 8 and 9 with 100% identity (DP47 light chain, SEQ ID NO: 157). See Appendix.
AMANN renders claims 1, 4, and 5 obvious because the claims only require SEQ ID NO: 8 or 9 and the present specification teaches that an antigen binding portion includes the VH or VL domain (p. 9, lines 8 – 23). Although AMANN does not teach that the antibody binds CD9B441, the VL domain has the same structure as claimed and thus would have the same function.
AMANN teaches a DP47 Fab. See p. 223-lines 1-5.
AMANN teaches a DP47 Fab. See p. 223-lines 1-5.
AMANN teaches making monoclonal antibodies See p. paragraph bridging pp. 93-94.
AMANN teaches chimeric and fully human form of the antibodies. See p. 94-line 5 to p. 95-line 5.
Regarding claim 17, AMANN discloses the protein (DP47 light chain, SEQ ID NO: 157) encoded by the nucleotide sequence of SEQ ID NO: 10. See Appendix.
Amman teaches nucleic acid vectors, host cells and methods of production of the antibody. See p. 17-lines -9-20.
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).
Thus, because AMANN discloses the protein encoded by SEQ ID NO: 10, AMANN renders the nucleotide sequence of claim 17, the vector of claim 19, the host cell of claims 20 – 21, and the method of producing the protein of claim 22 obvious.
Allowable Subject Matter
Claim 3 is allowed.
The prior art does not disclose an anti-idiotype antibody having the CDRs of present claim 3.
Claims 7 – 10 are 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.
The prior art does not disclose the sequences of SEQ ID NOs: 23 or 24 which are required by claims 7 and 9.
SEQ ID NOs: 25 and 26 of present claims 8 and 10 are disclosed in prior art that does not teach them within the context of an anti-idiotype antibody or antigen binding portion thereof that specifically binds a target antibody that comprises CD9B441. Thus, anti-idiotype antibody or antigen binding portion thereof that specifically binds a target antibody that comprises CD9B441 wherein the heavy chain has an amino acid sequence having at least 90% sequence identity to an amino acid sequence selected from the group consisting of SEQ ID NOs: 25 – 26 is free of the art.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1 – 2, 4 – 5, and 11 – 36 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 12, 16, 24, 36, 44, 47, 50, and 53 – 56 of copending Application No. 16/950,296 in view of LOBB and AMANN.
Copending claim 1 recites a chimeric antigen receptor (CAR) comprising:
Copending claim 16 recites a heavy chain variable region comprising an amino acid sequence of SEQ ID NO: 14 and a light chain variable region comprising an amino acid sequence of SEQ ID NO: 32.
Copending SEQ ID NO: 32 discloses present SEQ ID NO: 29 with 100% identity. Copending SEQ ID NO: 14 discloses present SEQ ID NO: 30 with 100% identity. See Appendix.
The main difference between the present claims and the copending claims is that the present claims recite an anti-idiotype antibody that binds to the VH and VL of the copending claims. However, LOBB discloses this difference. The teachings of LOBB and AMANN and how they relate to the claims, are set forth in the rejections under 35 U.S.C. 103 above.
Because the copending claims recite anti-CD79b (CD9B441) VH and VL, and LOBB discloses the anti-CD79b polypeptides as a target for an anti-idiotype antibody, it would have been obvious to one having ordinary skill in the art to use the copending claims’ anti-CD79b (CD9B441) polypeptides in the composition of the present claims.
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 1 – 2, 4 – 6, and 11 – 36 are rejected. Claim 3 is allowed. Claims 7 – 10 are objected to.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ESTELLA M. GUSTILO whose telephone number is (703)756-1706. The examiner can normally be reached Monday - Friday 9:00 AM - 5:00 PM.
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.
/ESTELLA M. GUSTILO/Examiner, Art Unit 1646
/PETER J REDDIG/Primary Examiner, Art Unit 1646
APPENDIX
Alignment with SEQ ID NO: 29
RESULT 1
US-16-950-296-32
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
Sequence 32, US/16950296
Publication No. US20210145878A1
GENERAL INFORMATION
APPLICANT: JANSSEN BIOTECH, INC.
TITLE OF INVENTION: ANTI-CD79 CHIMERIC ANTIGEN RECEPTORS, CAR-T CELLS, AND USES
TITLE OF INVENTION: THEREOF
FILE REFERENCE: JBI6171USNP1
CURRENT APPLICATION NUMBER: US/16/950,296
CURRENT FILING DATE: 2020-11-17
PRIOR APPLICATION NUMBER: 62/936,662
PRIOR FILING DATE: 2019-11-18
NUMBER OF SEQ ID NOS: 288
SEQ ID NO 32
LENGTH: 110
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic
polypeptide
Query Match 100.0%; Score 569; Length 110;
Best Local Similarity 100.0%;
Matches 110; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QSALTQPPSVSEAPRQRVTISCSGSASNIGNNGVNWYQQLPGKTPKLLIYNDDLLPSGVS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QSALTQPPSVSEAPRQRVTISCSGSASNIGNNGVNWYQQLPGKTPKLLIYNDDLLPSGVS 60
Qy 61 DRFSGSKSGTSASLAISGLQSEDEADYFCAAWDDSLNGLVFGGGTKLTVL 110
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DRFSGSKSGTSASLAISGLQSEDEADYFCAAWDDSLNGLVFGGGTKLTVL 110
Alignment with SEQ ID NO: 30
RESULT 1
US-16-950-296-14
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
Sequence 14, US/16950296
Publication No. US20210145878A1
GENERAL INFORMATION
APPLICANT: JANSSEN BIOTECH, INC.
TITLE OF INVENTION: ANTI-CD79 CHIMERIC ANTIGEN RECEPTORS, CAR-T CELLS, AND USES
TITLE OF INVENTION: THEREOF
FILE REFERENCE: JBI6171USNP1
CURRENT APPLICATION NUMBER: US/16/950,296
CURRENT FILING DATE: 2020-11-17
PRIOR APPLICATION NUMBER: 62/936,662
PRIOR FILING DATE: 2019-11-18
NUMBER OF SEQ ID NOS: 288
SEQ ID NO 14
LENGTH: 119
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Description of Artificial Sequence: Synthetic
polypeptide
Query Match 100.0%; Score 633; Length 119;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSKSGAWNWIRQSPSRGLEWLGRTYYRSKWY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLQQSGPGLVKPSQTLSLTCAISGDSVSSKSGAWNWIRQSPSRGLEWLGRTYYRSKWY 60
Qy 61 NEYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCTRVDTDFDYWGQGTLVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NEYAVSVKSRITINPDTSKNQFSLQLNSVTPEDTAVYYCTRVDTDFDYWGQGTLVTVSS 119
Alignment with SEQ ID NO: 31
RESULT 1
BJJ68021
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BJJ68021 standard; protein; 491 AA.
XX
AC BJJ68021;
XX
DT 08-JUL-2021 (first entry)
XX
DE Anti-CD79b chimeric antigen receptor (CAR) SEQ ID 180.
XX
KW AGM6; B-Cell-Specific Glycoprotein B29; CD137; CD79b; CDw137;
KW Cluster of Differentiation 79b protein; Ig-Beta;
KW T-cell CD3 glycoprotein zeta chain; T-cell surface CD8 alpha chain;
KW T-cell surface glycoprotein CD3 zeta chain;
KW TNF receptor superfamily member 9; cancer; cell therapy; cytostatic;
KW diagnostic test; fusion protein; immunotherapy; recombinant protein;
KW single chain antibody; therapeutic.
XX
OS Synthetic.
OS Unidentified.
XX
CC PN US2021145878-A1.
XX
CC PD 20-MAY-2021.
XX
CC PF 17-NOV-2020; 2020US-00950296.
XX
PR 18-NOV-2019; 2019US-0936662P.
XX
CC PA (JOHJ ) JANSSEN BIOTECH INC.
XX
CC PI Philippar U, Lasorsa E, Ganesan R;
XX
DR WPI; 2021-53872S/051.
XX
CC PT New chimeric antigen receptor useful in pharmaceutical composition for
CC PT killing targeted cancer cell, detecting presence of cancer or treating
CC PT human having cancer, preferably B-cell lymphoma or non-Hodgkin lymphoma.
XX
CC PS Claim 47; SEQ ID NO 180; 302pp; English.
XX
CC The present invention relates to a novel chimeric antigen receptor (CAR)
CC useful for treating cancer. The CAR comprises: (a) an extracellular
CC domain that specifically binds to the cluster of differentiation (CD) 79b
CC antigen; (b) a transmembrane domain; and (c) an intracellular signaling
CC domain optionally comprising at least one co-stimulatory domain. The
CC invention further relates to: (1) an isolated lymphocyte expressing the
CC CAR; (2) an isolated nucleic acid molecule encoding the CAR; (3) a vector
CC comprising the nucleic acid molecule; (4) a cell expressing the nucleic
CC acid molecule; (5) a method for killing a targeted cancer cell which
CC involves contacting the cancer cell with the lymphocyte; (6) a method for
CC detecting the presence of cancer in a subject; (7) a method for treating
CC a subject having cancer; and (8) a pharmaceutical composition comprising
CC an effective amount of the lymphocyte and a pharmaceutically acceptable
CC excipient. The extracellular antigen-binding domain comprises heavy chain
CC and light chain complementarity determining regions 1-3 (CDRs 1-3) and a
CC heavy chain variable region (VH) and a light chain variable region (VL)
CC respectively. The CAR is useful in a pharmaceutical composition for
CC killing a targeted cancer cell, detecting the presence of cancer in a
CC subject or treating a subject having cancer. The cancer is B-cell
CC lymphoma, non-Hodgkin lymphoma, diffuse large B-cell lymphoma (DLBCL),
CC mantle cell lymphoma (MCL), follicular lymphoma (FL), marginal zone
CC lymphoma (MZ), acute lymphoblastic leukemia (ALL), chronic lymphocytic
CC leukemia (CLL), multiple myeloma (MM), mucosa-associated lymphoid tissue
CC (MALT) lymphoma, Hodgkin's lymphoma, Burkitt's lymphoma, hairy-cell
CC leukemia, or plasmacytoma. The present sequence is a chimeric antigen
CC receptor (CAR) comprising a signal peptide, CD8 alpha hinge region, CD8
CC alpha transmembrane domain, an intracellular signaling domain comprising
CC TNF receptor superfamily member 9 (CD137) and CD3 zeta chain, and an anti
CC -CD79b single chain antibody (scFv), used in the present invention for
CC treating cancer.
XX
SQ Sequence 491 AA;
Query Match 100.0%; Score 2595; Length 491;
Best Local Similarity 100.0%;
Matches 491; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 MAWVWTLLFLMAAAQSIQAQSALTQPPSVSEAPRQRVTISCSGSASNIGNNGVNWYQQLP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 MAWVWTLLFLMAAAQSIQAQSALTQPPSVSEAPRQRVTISCSGSASNIGNNGVNWYQQLP 60
Qy 61 GKTPKLLIYNDDLLPSGVSDRFSGSKSGTSASLAISGLQSEDEADYFCAAWDDSLNGLVF 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GKTPKLLIYNDDLLPSGVSDRFSGSKSGTSASLAISGLQSEDEADYFCAAWDDSLNGLVF 120
Qy 121 GGGTKLTVLGGSEGKSSGSGSESKSTGGSQVQLQQSGPGLVKPSQTLSLTCAISGDSVSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GGGTKLTVLGGSEGKSSGSGSESKSTGGSQVQLQQSGPGLVKPSQTLSLTCAISGDSVSS 180
Qy 181 KSGAWNWIRQSPSRGLEWLGRTYYRSKWYNEYAVSVKSRITINPDTSKNQFSLQLNSVTP 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 KSGAWNWIRQSPSRGLEWLGRTYYRSKWYNEYAVSVKSRITINPDTSKNQFSLQLNSVTP 240
Qy 241 EDTAVYYCTRVDTDFDYWGQGTLVTVSSTSTPAPRPPTPAPTIASQPLSLRPEACRPAAG 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 EDTAVYYCTRVDTDFDYWGQGTLVTVSSTSTPAPRPPTPAPTIASQPLSLRPEACRPAAG 300
Qy 301 GAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQ 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 GAVHTRGLDFACDIYIWAPLAGTCGVLLLSLVITLYCKRGRKKLLYIFKQPFMRPVQTTQ 360
Qy 361 EEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGR 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 EEDGCSCRFPEEEEGGCELRVKFSRSADAPAYKQGQNQLYNELNLGRREEYDVLDKRRGR 420
Qy 421 DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 DPEMGGKPRRKNPQEGLYNELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTY 480
Qy 481 DALHMQALPPR 491
|||||||||||
Db 481 DALHMQALPPR 491
Alignment with SEQ ID NO: 8
RESULT 8
BDA21179
(NOTE: this sequence has 11 duplicates in the database searched.
See complete list at the end of this report)
ID BDA21179 standard; protein; 215 AA.
XX
AC BDA21179;
XX
DT 30-JUN-2016 (first entry)
XX
DE DP47 light chain, SEQ 157.
XX
KW cancer; cytostatic; protein production; protein therapy;
KW recombinant protein; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2016075278-A1.
XX
CC PD 19-MAY-2016.
XX
CC PF 13-NOV-2015; 2015WO-EP076528.
XX
PR 14-NOV-2014; 2014EP-00193260.
PR 03-SEP-2015; 2015EP-00183736.
PR 02-OCT-2015; 2015EP-00188142.
XX
CC PA (HOFF ) HOFFMANN LA ROCHE & CO AG F.
CC PA (HOFF ) HOFFMANN LA ROCHE INC.
XX
CC PI Amann M, Bruenker P, Claus C, Ferrara Koller C, Grau-Richards S;
CC PI Klein C, Levitsky V, Moessner E, Regula JT, Umana P;
XX
DR WPI; 2016-29508H/38.
XX
CC PT Tumor necrosis factor family ligand trimer-containing antigen binding
CC PT molecule used in pharmaceutical composition for preparing medicament for
CC PT treating disease i.e. cancer, comprises moiety capable of specific
CC PT binding to target cell antigen.
XX
CC PS Disclosure; SEQ ID NO 157; 438pp; English.
XX
CC The present invention relates to a novel tumor necrosis factor (TNF)
CC family ligand trimer-containing antigen binding molecule, which comprises
CC a moiety capable of specific binding to a target cell antigen, and first
CC and second polypeptides that are linked to each other by a disulfide
CC bond. The first polypeptide comprises two ectodomains of TNF ligand
CC family member that are connected to each other by peptide linker. The
CC second polypeptide comprises one ectodomain of TNF ligand family member.
CC The invention also provides: an isolated polynucleotide encoding the TNF
CC family ligand trimer-containing antigen binding molecule; a vector
CC comprising the isolated polynucleotide; a host cell comprising the
CC isolated polynucleotide or the vector; a method for producing the TNF
CC family ligand trimer-containing antigen binding molecule; a
CC pharmaceutical composition comprising the TNF family ligand trimer-
CC containing antigen binding molecule; and a method for treating cancer.
CC The present sequence represents a DP47 light chain, which can be useful
CC for preparing the TNF family ligand trimer-containing antigen binding
CC molecule of the invention.
XX
SQ Sequence 215 AA;
Query Match 100.0%; Score 555; Length 215;
Best Local Similarity 100.0%;
Matches 108; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIP 60
Qy 61 DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGQGTKVEIK 108
||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGQGTKVEIK 108
Alignment with SEQ ID NO: 9
RESULT 1
BDA21179
(NOTE: this sequence has 11 duplicates in the database searched.
See complete list at the end of this report)
ID BDA21179 standard; protein; 215 AA.
XX
AC BDA21179;
XX
DT 30-JUN-2016 (first entry)
XX
DE DP47 light chain, SEQ 157.
XX
KW cancer; cytostatic; protein production; protein therapy;
KW recombinant protein; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2016075278-A1.
XX
CC PD 19-MAY-2016.
XX
CC PF 13-NOV-2015; 2015WO-EP076528.
XX
PR 14-NOV-2014; 2014EP-00193260.
PR 03-SEP-2015; 2015EP-00183736.
PR 02-OCT-2015; 2015EP-00188142.
XX
CC PA (HOFF ) HOFFMANN LA ROCHE & CO AG F.
CC PA (HOFF ) HOFFMANN LA ROCHE INC.
XX
CC PI Amann M, Bruenker P, Claus C, Ferrara Koller C, Grau-Richards S;
CC PI Klein C, Levitsky V, Moessner E, Regula JT, Umana P;
XX
DR WPI; 2016-29508H/38.
XX
CC PT Tumor necrosis factor family ligand trimer-containing antigen binding
CC PT molecule used in pharmaceutical composition for preparing medicament for
CC PT treating disease i.e. cancer, comprises moiety capable of specific
CC PT binding to target cell antigen.
XX
CC PS Disclosure; SEQ ID NO 157; 438pp; English.
XX
CC The present invention relates to a novel tumor necrosis factor (TNF)
CC family ligand trimer-containing antigen binding molecule, which comprises
CC a moiety capable of specific binding to a target cell antigen, and first
CC and second polypeptides that are linked to each other by a disulfide
CC bond. The first polypeptide comprises two ectodomains of TNF ligand
CC family member that are connected to each other by peptide linker. The
CC second polypeptide comprises one ectodomain of TNF ligand family member.
CC The invention also provides: an isolated polynucleotide encoding the TNF
CC family ligand trimer-containing antigen binding molecule; a vector
CC comprising the isolated polynucleotide; a host cell comprising the
CC isolated polynucleotide or the vector; a method for producing the TNF
CC family ligand trimer-containing antigen binding molecule; a
CC pharmaceutical composition comprising the TNF family ligand trimer-
CC containing antigen binding molecule; and a method for treating cancer.
CC The present sequence represents a DP47 light chain, which can be useful
CC for preparing the TNF family ligand trimer-containing antigen binding
CC molecule of the invention.
XX
SQ Sequence 215 AA;
Query Match 100.0%; Score 1125; Length 215;
Best Local Similarity 100.0%;
Matches 215; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EIVLTQSPGTLSLSPGERATLSCRASQSVSSSYLAWYQQKPGQAPRLLIYGASSRATGIP 60
Qy 61 DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGQGTKVEIKRADAAPTVSIFP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DRFSGSGSGTDFTLTISRLEPEDFAVYYCQQYGSSPLTFGQGTKVEIKRADAAPTVSIFP 120
Qy 121 PSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 PSSEQLTSGGASVVCFLNNFYPKDINVKWKIDGSERQNGVLNSWTDQDSKDSTYSMSSTL 180
Qy 181 TLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC 215
|||||||||||||||||||||||||||||||||||
Db 181 TLTKDEYERHNSYTCEATHKTSTSPIVKSFNRNEC 215
Alignment with protein encoded by SEQ ID NO: 10
RESULT 1
BDA21179
(NOTE: this sequence has 11 duplicates in the database searched.
See complete list at the end of this report)
ID BDA21179 standard; protein; 215 AA.
XX
AC BDA21179;
XX
DT 30-JUN-2016 (first entry)
XX
DE DP47 light chain, SEQ 157.
XX
KW cancer; cytostatic; protein production; protein therapy;
KW recombinant protein; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2016075278-A1.
XX
CC PD 19-MAY-2016.
XX
CC PF 13-NOV-2015; 2015WO-EP076528.
XX
PR 14-NOV-2014; 2014EP-00193260.
PR 03-SEP-2015; 2015EP-00183736.
PR 02-OCT-2015; 2015EP-00188142.
XX
CC PA (HOFF ) HOFFMANN LA ROCHE & CO AG F.
CC PA (HOFF ) HOFFMANN LA ROCHE INC.
XX
CC PI Amann M, Bruenker P, Claus C, Ferrara Koller C, Grau-Richards S;
CC PI Klein C, Levitsky V, Moessner E, Regula JT, Umana P;
XX
DR WPI; 2016-29508H/38.
XX
CC PT Tumor necrosis factor family ligand trimer-containing antigen binding
CC PT molecule used in pharmaceutical composition for preparing medicament for
CC PT treating disease i.e. cancer, comprises moiety capable of specific
CC PT binding to target cell antigen.
XX
CC PS Disclosure; SEQ ID NO 157; 438pp; English.
XX
CC The present invention relates to a novel tumor necrosis factor (TNF)
CC family ligand trimer-containing antigen binding molecule, which comprises
CC a moiety capable of specific binding to a target cell antigen, and first
CC and second polypeptides that are linked to each other by a disulfide
CC bond. The first polypeptide comprises two ectodomains of TNF ligand
CC family member that are connected to each other by peptide linker. The
CC second polypeptide comprises one ectodomain of TNF ligand family member.
CC The invention also provides: an isolated polynucleotide encoding the TNF
CC family ligand trimer-containing antigen binding molecule; a vector
CC comprising the isolated polynucleotide; a host cell comprising the
CC isolated polynucleotide or the vector; a method for producing the TNF
CC family ligand trimer-containing antigen binding molecule; a
CC pharmaceutical composition comprising the TNF family ligand trimer-
CC containing antigen binding molecule; and a method for treating cancer.
CC The present sequence represents a DP47 light chain, which can be useful
CC for preparing the TNF family ligand trimer-containing antigen binding
CC molecule of the invention.
XX
SQ Sequence 215 AA;
Alignment Scores:
Length: 215
Score: 1125.00 Matches: 215
Percent Similarity: 100.0% Conservative: 0
Best Local Similarity: 100.0% Mismatches: 0
Query Match: 91.8% Indels: 0
Gaps: 0
US-17-825-244-10 (1-645) x BDA21179 (1-215)
Qy 1 GAAATTGTGCTGACCCAGAGCCCGGGCACCCTGAGCCTGAGCCCGGGCGAACGCGCGACC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GluIleValLeuThrGlnSerProGlyThrLeuSerLeuSerProGlyGluArgAlaThr 20
Qy 61 CTGAGCTGCCGCGCGAGCCAGAGCGTGAGCAGCAGCTATCTGGCGTGGTATCAGCAGAAA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 21 LeuSerCysArgAlaSerGlnSerValSerSerSerTyrLeuAlaTrpTyrGlnGlnLys 40
Qy 121 CCGGGCCAGGCGCCGCGCCTGCTGATTTATGGCGCGAGCAGCCGCGCGACCGGCATTCCG 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 41 ProGlyGlnAlaProArgLeuLeuIleTyrGlyAlaSerSerArgAlaThrGlyIlePro 60
Qy 181 GATCGCTTTAGCGGCAGCGGTTCCGGCACCGATTTTACCCTGACCATTAGCCGCCTGGAA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AspArgPheSerGlySerGlySerGlyThrAspPheThrLeuThrIleSerArgLeuGlu 80
Qy 241 CCGGAAGATTTTGCGGTGTATTATTGCCAGCAGTATGGCAGCAGCCCGCTGACCTTTGGC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 81 ProGluAspPheAlaValTyrTyrCysGlnGlnTyrGlySerSerProLeuThrPheGly 100
Qy 301 CAGGGCACCAAAGTGGAAATTAAACGGGCTGATGCTGCACCGACTGTGTCCATCTTCCCA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 101 GlnGlyThrLysValGluIleLysArgAlaAspAlaAlaProThrValSerIlePhePro 120
Qy 361 CCATCCAGTGAGCAGTTAACATCTGGAGGTGCCTCAGTCGTGTGCTTCTTGAACAACTTC 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ProSerSerGluGlnLeuThrSerGlyGlyAlaSerValValCysPheLeuAsnAsnPhe 140
Qy 421 TACCCCAAAGACATCAATGTCAAGTGGAAGATTGATGGCAGTGAACGACAAAATGGCGTC 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 141 TyrProLysAspIleAsnValLysTrpLysIleAspGlySerGluArgGlnAsnGlyVal 160
Qy 481 CTGAACAGTTGGACTGATCAGGACAGCAAAGACAGCACCTACAGCATGAGCAGCACCCTC 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 161 LeuAsnSerTrpThrAspGlnAspSerLysAspSerThrTyrSerMetSerSerThrLeu 180
Qy 541 ACGTTGACCAAGGACGAGTATGAACGACATAACAGCTATACCTGTGAGGCCACTCACAAG 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 ThrLeuThrLysAspGluTyrGluArgHisAsnSerTyrThrCysGluAlaThrHisLys 200
Qy 601 ACATCAACTTCACCCATTGTCAAGAGCTTCAACAGGAATGAGTGT 645
|||||||||||||||||||||||||||||||||||||||||||||
Db 201 ThrSerThrSerProIleValLysSerPheAsnArgAsnGluCys 215