Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
DETAILED ACTION
2. Claims 1-16 are pending and currently under prosecution.
Priority
Applicant’s claim under 35 U.S.C. §§ 119(e) and 365(c) for benefit of the earlier filing date of applications, is acknowledged.
Claim Objections
4. Claims 11 and 16 are objected to because claim recites, “formula (I) of WO 2019/215316”, “Table 1 of WO 2020/127960”. Claims must, under modern claim practice, stand alone to define invention, and incorporation into claims by express reference to specification and/or drawings is not permitted except in very limited circumstances. See Ex parte Fressola, 27 USPQ2d 1608 (BPAI, 1993). See M.P.E.P. § 2173.05(s), which states:
“Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant's convenience.” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993) (citations omitted).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
5. 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.
6. 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. Claim 1 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention.
Claim 1 recites the limitation "the TGFβ inhibitor" in line 3. There is insufficient antecedent basis for this limitation in the claim.
. The following is a quotation 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.
8. The following is a quotation of 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
9. Claims 1, 6, 10 and 13 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
This is a “written description” rejection.
The considerations that are made in determining whether a claimed invention is supported by an adequate written description are outlined by the published Guidelines for Examination of Patent Applications Under the 35 U.S.C. 112, para. 1, ``Written Description'' Requirement (Federal Register; Vol. 66, No. 4, January 5, 2001; The 2015 Written Description Workshop materials; hereinafter “Guidelines”).
These guidelines state that rejection of a claim for lack of written description, where the claim recites the language of an original claim should be rare. Nevertheless, these guidelines further state, “the issue of a lack of written description may arise even for an original claim when an aspect of the claimed invention has not been described with sufficient particularity such that one skilled in the art would recognize that the applicant has possession of the claimed invention” (Id. at 1105). The “Guidelines” continue:
The claimed invention as a whole may not be adequately described if the claims require an essential or critical feature which is not adequately described in the specification and which is not conventional in the art or known to one of ordinary skill in the art. This problem may arise where an invention is described solely in terms of a method of its making coupled with its function and there is no described or art-recognized correlation or relationship between the structure of the invention and its function. A lack of adequate written description issue also arises if the knowledge and level of skill in the art would not permit one skilled in the art to immediately envisage the product claimed from the disclosed process.
With further regard to the proposition that, as original claims, the claims themselves provide in haec verba support sufficient to satisfy the written description requirement, the Federal Circuit has explained that in ipsis verbis support for the claims in the specification does not per se establish compliance with the written description requirement:
Even if a claim is supported by the specification, the language of the specification, to the extent possible, must describe the claimed invention so that one skilled in the art can recognize what is claimed. The appearance of mere indistinct words in a specification or a claim, even an original claim, does not necessarily satisfy that requirement. The disclosure must allow one skilled in the art to visualize or recognize the identity of the subject matter purportedly described. Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
Regents of the University of California v. Eli Lilly & Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997). See also: University of Rochester v. G.D. Searle & Co., 69 USPQ2d 1886 1892 (CA FC 2004).
Thus, an original claim may provide written description for itself, but it must still be an adequate written description, which establishes that the inventor was in possession of the invention.
The claims 1, 10 and 13 are herein drawn to a method comprising PD-1 inhibitor, TGFβ inhibitor and MCT4 inhibitor for treating cancer.
In this instance, the claims are directed to a genus of PD-1 inhibitor, TGFβ inhibitor and MCT4 inhibitor for treating cancer.
A genus of PD-1 inhibitor, TGFβ inhibitor and MCT4 inhibitor may include, for example, a polypeptide, an antibody, a nucleic acid, or small molecule.
The claim 6 is herein drawn to a fusion protein have at least 90% sequence identity to SEQ ID NOs: 7-8, 15 and 17-18. Thus, claim 6 is directed to a genus of fusion protein have at least 90% sequence identity to SEQ ID NOs: 7-8, 15 and 17-18.
Although the specification teaches anti-PD-L1 antibody (see [0059] of the published application), TGFβRII (see [0069] of the published application), and a small molecule inhibitor of MCT4 (see [0053] of the published application), and SEQ ID NOs: 7-8, 15 and 17-18; however, it is not representative of the claimed a genus of PD-1 inhibitor, TGFβ inhibitor and MCT4 inhibitor, and a genus of fusion protein have at least 90% sequence identity to SEQ ID NOs: 7-8, 15 and 17-18. This is because the claimed PD-1 inhibitor, TGFβ inhibitor and MCT4 inhibitor, for example, a polypeptide, an antibody, a nucleic acid, or small molecule have markedly different structures. The artisan would not expect that any given PD-1 inhibitor, TGFβ inhibitor and MCT4 inhibitor would have activity for treating cancer, and a fusion protein have at least 90% sequence identity to SEQ ID NOs: 7-8, 15 and 17-18 would have or retain the activity or function of SEQ ID NOs: 7-8, 15 and 17-18.
Guidelines states, “[p]ossession may be shown in a variety of ways including description of an actual reduction to practice, or by showing the invention was ‘ready for patenting’ such as by disclosure of drawings or structural chemical formulas that show that the invention was complete, or by describing distinguishing identifying characteristics sufficient to show that the applicant was in possession of the claimed invention” (Id. at 1104). “Guidelines” further states, “[f]or inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus” (Id. at 1106); accordingly, it follows that an adequate written description of a genus cannot be achieved in the absence of a disclosure of at least one species within the genus. Moreover, because the claims encompass a genus of PD-1 inhibitor, TGFβ inhibitor, MCT4 inhibitor, and fusion protein have at least 90% sequence identity to SEQ ID NOs: 7-8, 15 and 17-18 for treating cancer, which vary both structurally and functionally, an adequate written description of the claimed invention must include sufficient description of at least a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics sufficient to show that Applicant was in possession of the claimed genus. In this instance, factual evidence of an actual reduction to practice has not been disclosed by Applicant in the specification; Applicant has not shown the invention was “ready for patenting” by disclosure of drawings or structural chemical formulas that show that the invention was complete; and Applicant has not described distinguishing identifying characteristics sufficient to show that Applicant was in possession of the claimed invention at the time the application was filed.
Thus, it is submitted that the instant claims, and the disclosure describing the claimed subject matter, fails to satisfy the written description requirement set forth under 35 U.S.C. § 112, first paragraph.
10. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
Claim Rejections - 35 USC § 103
11. The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102 of this title, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
12. The factual inquiries set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
13. Claims 1-16 are rejected under 35 U.S.C. 103 as being unpatentable over Lo et al. (WO 2018/029367, published on 15 February 2018, IDS) in view of Goldberg et al. (WO 2019/215316, published on 14 November 2019, IDS).
Claims 1-16 are herein drawn to a method of treating cancer in a subject, comprising administering a PD-1 inhibitor, TGFβ inhibitor and MCT4 inhibitor to the subject, wherein the PD-1 inhibitor and the TGFβ inhibitor are fused as an anti-PD(L)1: TGFβ fusion protein.
Lo et al. teach a method of treating cancer, the method comprising administering to a cancer patient a fusion protein comprising a human TGFβRII and an anti-PD-L1 antibody, and an additional anti-cancer agent; see entire document, e.g., abstract, [0052], [00168], Examples 3-4, claims 20-21.
Lo et al. teach the sequences of heavy chain three CDRs and light chain three CDRs (see [0092]), which are the same as the instant claimed SEQ ID NOs: 1-6.
Lo et al. teach anti-PD-L1 antibody-TGFβRII fusion protein comprising the light chain of the anti-PD-L1 antibody (SEQ ID NO: 1) and the heavy chain of the molecule (SEQ ID NO: 3) which is a fusion protein comprising the heavy chain of the anti-PD-L1 antibody genetically fused to via a flexible (Gly4Ser)4Gly linker to the N-terminus of the extracellular domain (ECD) of TGFβRII; see [0038], [00168], Fig. 1.
SEQ ID NOs: 1 and 3 of Lo et al. are 100% identical with the instant claimed SEQ ID NOs: 7-8; see below sequence alignment.
The instant specification teaches that “bintrafusp alfa”, also known as M7824, is an anti-PD-L1:TGFβRII fusion protein; see [0036] of the published application. Lo et al. teach M7824; see Fig. 9B and Fig. 9C.
Lo et al. teach dosages of the anti-PD-L1 antibody-TGFβRII fusion protein; see [00175].
Lo et al. teach cancer includes cancer of colorectal, breast, ovarian, pancreatic, gastric, prostate, renal, cervical, myeloma, lymphoma, leukemia, or thyroid; see [0029]
Lo et al. do not teach the additional anti-cancer agent is a MCT4 inhibitor.
However, these deficiencies are remedied by Goldberg et al.
Goldberg et al. teach MCT4 inhibitors (e.g., compounds of Formula (I)) for using in treating cancer; see entire document, e.g., title, abstract, pages 3-4, claims 10-16.
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of the references so as to treat cancer comprising a combination of anti-PD-L1 antibody-TGFβRII fusion protein and a MCT4 inhibitor. One would have been motivated to do so because Lo et al. teach a method of treating cancer, the method comprising administering to a cancer patient an anti-PD-L1 antibody-TGFβRII fusion protein and an additional anti-cancer agent; Goldberg et al. teach MCT4 inhibitors for using in treating cancer. Thus, one of ordinary skill in the art would have a reasonable expectation of success that by combining the teachings of the references so as to substitute the additional anti-cancer agent of Lo et al. with a MCT4 inhibitor of Goldberg et al., because simple substitution of the anti-cancer agent of Lo et al. for another anti-cancer agent of Goldberg et al. would obtain predictable results.
Given the examination guidelines for determining obviousness under 35 U.S.C. 103 in view of the Supreme Court decision in KSR International Co. V. Teleflex Inc. 82 USPQ2d 1385 (2007) and the Examination Guidelines set forth in the Federal Register (Vol. 72, No. 195, October 10, 2007) and incorporated recently into the MPEP (Revision 9, March 2014), the following rationales to support rejection under 35 U.S.C. 103(a) are noted:
A) Combining prior art elements according known methods to yield predictable results.
B) Simple substitution of one known element for another to obtain predictable results.
C) Use of known technique to improve similar devices (methods, or products) in the same way.
D) Applying known technique to a known device (method, or product) ready for improvement to yield predictable results.
E) “Obvious to try” --- choosing form a finite number of identified, predictable solutions, with a reasonable expectation of success.
(F) Known work in one field of endeavor may prompt variations of it for use in either the same field or a different one based on design incentives or other market forces if the variations are predictable to one of ordinary skill in the art.
G) Some teachings, suggestion, or motivation in the prior art that would lead to one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.
In this case, simple substitution of the anti-cancer agent of Lo et al. for another anti-cancer agent of Goldberg et al. would obtain predictable results.
Obviousness is not the result of a rigid formula disassociated from the consideration of the facts of a case. Indeed, the common sense of those skilled in the art demonstrates why some combinations would have been obvious where others would not. See KSR International Co. V. Teleflex Inc. 82 USPQ2d 1385 (2007). From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention.
Conclusion
14. No claim is allowed.
15. Any inquiry concerning this communication or earlier communications from the examiner should be directed to YAN XIAO whose telephone number is (571)270-3578. The examiner can normally be reached M-F 8-5 EST.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached on 571-270-3503. 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.
/YAN XIAO/Primary Examiner, Art Unit 1642
Sequence alignment
BFC04391 standard; protein; 216 AA.
XX
AC BFC04391;
XX
DT 05-APR-2018 (first entry)
XX
DE Anti-PD-L1 human antibody lambda light chain protein sequence, SEQ ID 1.
XX
KW Immunoglobulin lambda; PD-L1 protein; Programmed cell death ligand 1;
KW antibody; cancer; cytostatic; growth; light chain; protein therapy;
KW therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2018029367-A1.
XX
CC PD 15-FEB-2018.
XX
CC PF 11-AUG-2017; 2017WO-EP070513.
XX
PR 12-AUG-2016; 2016US-0374621P.
XX
CC PA (MERE ) MERCK PATENT GMBH.
XX
CC PI Lo K, Lan Y;
XX
DR WPI; 2018-13154G/13.
DR N-PSDB; BFC04394.
XX
CC PT Pharmaceutical composition used for treating cancer, where cancer is
CC PT selected from group consisting of colorectal, and breast, comprises
CC PT protein comprising human TGFpRIL or fragment capable of binding
CC PT transforming growth factor P.
XX
CC PS Claim 6; SEQ ID NO 1; 78pp; English.
XX
CC The present invention relates to a novel pharmaceutical composition,
CC useful for treating cancer. The pharmaceutical composition comprises: a)
CC a human transforming growth factor P receptor II (TGFpRII); or a fragment
CC capable of binding TGFP; and b) an antibody, or an antigen-binding
CC fragment, which binds to a human programmed death ligand 1 (PD-L1) in
CC combination with an additional anti-cancer agent, for treating cancer.
CC The invention further relates to: 1) a method for treating cancer; and 2)
CC a method for inhibiting tumor growth. The novel pharmaceutical
CC composition of the invention is useful for treating cancer such as
CC colorectal cancer, breast cancer, ovarian cancer, pancreatic cancer,
CC gastric cancer, prostate cancer, renal cancer, cervical cancer, myeloma,
CC lymphoma, leukemia, thyroid cancer, endometrial cancer, uterine cancer,
CC bladder cancer, neuroendocrine cancer, head and neck cancer, liver
CC cancer, nasopharyngeal cancer, testicular cancer, small cell lung cancer,
CC non-small cell lung cancer, melanoma, basal cell skin cancer, squamous
CC cell skin cancer, dermatofibrosarcoma, protuberans, Merkel cell
CC carcinoma, glioblastoma, glioma, sarcoma, mesothelioma, and
CC myelodysplasia syndromes. The present sequence is an anti-human PD-L1
CC human antibody lambda light chain protein sequence, whose complete
CC antibody is useful for treating cancer.
Query Match 100.0%; Score 1127; Length 216;
Best Local Similarity 100.0%;
Matches 216; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGV 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QSALTQPASVSGSPGQSITISCTGTSSDVGGYNYVSWYQQHPGKAPKLMIYDVSNRPSGV 60
Qy 61 SNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTRVFGTGTKVTVLGQPKANPTVT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 SNRFSGSKSGNTASLTISGLQAEDEADYYCSSYTSSSTRVFGTGTKVTVLGQPKANPTVT 120
Qy 121 LFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LFPPSSEELQANKATLVCLISDFYPGAVTVAWKADGSPVKAGVETTKPSKQSNNKYAASS 180
Qy 181 YLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 216
||||||||||||||||||||||||||||||||||||
Db 181 YLSLTPEQWKSHRSYSCQVTHEGSTVEKTVAPTECS 216
BFC04393 standard; protein; 607 AA.
XX
AC BFC04393;
XX
DT 05-APR-2018 (first entry)
XX
DE Anti-human PD-L1 antibody-TGFpRII fusion protein sequence, SEQ ID 3.
XX
KW Immunoglobulin lambda; PD-L1 protein; Programmed cell death ligand 1;
KW TGFpRII protein; antibody; cancer; cytostatic; fusion protein; growth;
KW protein therapy; therapeutic; transforming growth factor P receptor II.
XX
OS Homo sapiens.
OS Synthetic.
XX
CC PN WO2018029367-A1.
XX
CC PD 15-FEB-2018.
XX
CC PF 11-AUG-2017; 2017WO-EP070513.
XX
PR 12-AUG-2016; 2016US-0374621P.
XX
CC PA (MERE ) MERCK PATENT GMBH.
XX
CC PI Lo K, Lan Y;
XX
DR WPI; 2018-13154G/13.
DR N-PSDB; BFC04395.
XX
CC PT Pharmaceutical composition used for treating cancer, where cancer is
CC PT selected from group consisting of colorectal, and breast, comprises
CC PT protein comprising human TGFpRIL or fragment capable of binding
CC PT transforming growth factor P.
XX
CC PS Claim 6; SEQ ID NO 3; 78pp; English.
XX
CC The present invention relates to a novel pharmaceutical composition,
CC useful for treating cancer. The pharmaceutical composition comprises: a)
CC a human transforming growth factor P receptor II (TGFpRII); or a fragment
CC capable of binding TGFP; and b) an antibody, or an antigen-binding
CC fragment, which binds to a human programmed death ligand 1 (PD-L1) in
CC combination with an additional anti-cancer agent, for treating cancer.
CC The invention further relates to: 1) a method for treating cancer; and 2)
CC a method for inhibiting tumor growth. The novel pharmaceutical
CC composition of the invention is useful for treating cancer such as
CC colorectal cancer, breast cancer, ovarian cancer, pancreatic cancer,
CC gastric cancer, prostate cancer, renal cancer, cervical cancer, myeloma,
CC lymphoma, leukemia, thyroid cancer, endometrial cancer, uterine cancer,
CC bladder cancer, neuroendocrine cancer, head and neck cancer, liver
CC cancer, nasopharyngeal cancer, testicular cancer, small cell lung cancer,
CC non-small cell lung cancer, melanoma, basal cell skin cancer, squamous
CC cell skin cancer, dermatofibrosarcoma, protuberans, Merkel cell
CC carcinoma, glioblastoma, glioma, sarcoma, mesothelioma, and
CC myelodysplasia syndromes. The present sequence is an anti-PD-L1 antibody-
CC TGFpRII (anti-PD-L1/TGFp Trap) fusion protein, useful for treating
CC cancer.
Query Match 100.0%; Score 3267; Length 607;
Best Local Similarity 100.0%;
Matches 607; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYIMMWVRQAPGKGLEWVSSIYPSGGITFY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYIMMWVRQAPGKGLEWVSSIYPSGGITFY 60
Qy 61 ADTVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARIKLGTVTTVDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADTVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARIKLGTVTTVDYWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELLGG 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSGGGGSGIPPHVQKSV 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGAGGGGSGGGGSGGGGSGGGGSGIPPHVQKSV 480
Qy 481 NNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKND 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 NNDMIVTDNNGAVKFPQLCKFCDVRFSTCDNQKSCMSNCSITSICEKPQEVCVAVWRKND 540
Qy 541 ENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEE 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 ENITLETVCHDPKLPYHDFILEDAASPKCIMKEKKKPGETFFMCSCSSDECNDNIIFSEE 600
Qy 601 YNTSNPD 607
|||||||
Db 601 YNTSNPD 607