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 of Group 3, claims 227-245 a) a first polypeptide comprising an extracellular domain of TNFR1; b) a second polypeptide comprising a TNFR1 transmembrane domain polypeptide; C) a third polypeptide comprising a 4-1BB cytosolic costimulatory signaling domain polypeptide; and d) a B-cell maturation antigen (BCMA) in the reply filed on October 22, 2024 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
2. Claims 128, 171, and 227-247 are pending.
3. Claims 128, 171, 246 and 247 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected inventions, there being no allowable generic or linking claim.
4. Claims 227-245 are currently under consideration as drawn to the elected species.
Priority
5. Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, or 365(c) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of the first paragraph of 35 U.S.C. 112. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosure of the prior-filed Application No. 62/900,911 fails to provide adequate support or enablement in the manner provided by the first paragraph of 35 U.S.C. 112 for one or more claims of this application. Examiner has established a priority date of September 16, 2020 for claims 227-245 because the claims as currently constituted recite (b) a T cell-antigen coupler (TAC) polypeptide comprising (i) an antigen-binding domain, (ii) a domain that binds a protein associated with a TCR complex, and (iii) a transmembrane and cytosolic domain of a T cell co- receptor and a review of the parent Application does not reveal support for the broadly the claimed limitations. Applicant is invited to submit evidence pointing to the serial number, page and line where support can be found establishing an earlier priority date.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
6. Claim 228 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 228 is drawn to the engineered T cell of claim 227, wherein the first polypeptide of the CCR comprises an extracellular domain of a TNFRSF member having a death domain. Claim 227 is drawn to a first polypeptide comprising an extracellular domain of a member of the Tumor Necrosis Factor Receptor Superfamily (TNFRSF) that binds tumor necrosis alpha (TNFa). Thus claim 228 fails to include all of the limitations of claim 227, i.e. that the extracellular domain binds tumor necrosis alpha (TNFa).
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
7. Claim 227-245 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.
MPEP § 2163 states that 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, 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. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus takes into account the state of the art at the time of the invention. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species.” Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
On 22 February 2018, the USPTO provided a Memorandum clarifying the Written Description Guidelines for claims drawn to antibodies, which can be found at www.uspto.gov/sites/default/files/documents/amgen_22feb2018.pdf. That Memorandum indicates that, in compliance with recent legal decisions, the disclosure of a fully characterized antigen no longer is sufficient written description of an antibody to that antigen. Accordingly, the instant claims have been evaluated in view of that guidance.
Scope of the claimed genus
The claims are drawn to an engineered T cell comprising: (a) a Chimeric Costimulatory Receptor (CCR) polypeptide comprising: (i) a first polypeptide comprising an extracellular domain of a member of the Tumor Necrosis Factor Receptor Superfamily (TNFRSF) that binds tumor necrosis alpha (TNFa) (ii) a second polypeptide comprising a transmembrane domain polypeptide; and (iii) a third polypeptide comprising a cytosolic costimulatory signaling domain polypeptide; and (b) a T cell-antigen coupler (TAC) polypeptide comprising (i) an antigen-binding domain, (ii) a domain that binds a protein associated with a TCR complex, and (iii) a transmembrane and cytosolic domain of a T cell co-receptor.
The TAC domain that binds a protein associated with a TCR complex is not limited to any particular type of binding domain that binds any protein associated with a TCR complex. Although claim 243 recites that the binding domain is derived from UCHT1, this includes any domain or subdomain of the UCHT1 antibody, e.g. a single CDR domain. Thus, the claims encompass a large genus of TAC domain that binds a protein associated with a TCR complex.
State of the Relevant Art
US 2016/0368964 A1 (Bramson et al. Dec. 22, 2016), “Bramson” teaches TACs with a UCHT1 scFv binding domain that binds CD3e . See Examples 1 and 2 and Fig. 1. Bramson does not teach other TAC domain that binds a protein associated with a TCR complex.
Overall, at the time the invention was made, the level of skill for preparing binding domains like antibodies and then selecting those domains with desired functional properties was high. However, even if a selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010); see also Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1876 (Fed. Cir. 2011) (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”) Absent a conserved structure, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what a TAC domain that binds a protein associated with a TCR complex would look like structurally.
Summary of Species disclosed in the original specification
The specification teaches the CD3 antigen binding domain is derived from UCHT1. See ¶ 0134 of the published application.
Are the disclosed species representative of the claimed genus?
MPEP § 2163 states that 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.
The specification discloses the UCHT1 antibody. The specification does not actually produce any other domains or antibodies that bind a protein associated with a TCR complex. Antibodies produced by different methods, such as in different species or in phage, would have been generally expected to be highly structurally diverse, particularly in the CDR sequences. Additionally non-antibody binding domains, e.g. ligand binding domains, would differ significantly in structure from an antibody like the UCHT1 antibody Applicant has described one species of a domain that binds a protein associated with a TCR complex. Given the breadth of the claimed genus, the described species therefore cannot be considered representative of a domain that binds a protein associated with a TCR complex.
Identifying characteristics and structure/function correlation
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied 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. To meet this requirement in the instant case, the specification must describe structural features that convey the claimed binding activity.
As noted above, the specification discloses the UCHT1 antibody But the specification does not describe what structures confer the binding activity claimed that would allow binding to any protein associated with a TCR complex. Accordingly, the skilled artisan would not be able to discern a structure/function correlation for that the genus of domains that bind a protein associated with a TCR complex.
For all of the reasons presented above, one of skill in the art would not know which of the countless other domains encompassed by the claims would also be able to bind a protein associated with a TCR complex. Neither the specification nor the dependent claims provide sufficient additional structure or a structure/function correlation to provide an adequate written description of the genus claimed. Therefore, the skilled artisan would not reasonably conclude that the inventors, at the time the application was filed, had full possession of a domain that binds a protein associated with a TCR complex as broadly claimed. Given the lack of shared structural properties that provide the claimed binding activity, the limited species described, and the fact that the species that were described cannot be considered representative of the broad genus, Applicant was not in possession of the invention as broadly claimed.
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.
8. Claim(s) 227-245 is/are rejected under 35 U.S.C. 103 as being unpatentable over US 2016/0368964 A1 (Bramson et al. Dec. 22, 2016), “Bramson” in view of WO 2020/163755 A9 (Cobbold et al. Aug. 13, 2020, filed Feb. 7, 2020), “Cobbold”.
Bramson teaches a trifunctional molecule comprising a target-specific ligand, a ligand that binds a protein associated with the TCR complex and a T cell receptor signaling domain polypeptide is provided. Engineering T cells with this novel receptor engenders antigen specific activation of numerous T cell functions, including cytokine production, degranulation and cytolysis. See abstract.
Bramson teaches a nucleic acid comprising: a. a first polynucleotide encoding a target-specific ligand; b. a second polynucleotide encoding a ligand that binds a protein associated with the TCR complex; and c. a third polynucleotide encoding a T cell receptor signaling domain polypeptide, the encoded polypeptide and T cells expressing the trifunctional T cell-antigen coupler. See ¶¶ 0007-0014, claims 1-13 and Fig. 1 A-B.
Bramson teaches a T cell includes T helper cells, cytotoxic T cells, memory T cells, regulatory T cells and natural killer T cells. See ¶¶ 0054
Bramson teaches the trifunctional T cell-antigen coupler binds the cancer antigen BCMA. See ¶¶ 0072-0073.
Bramson teaches the protein associated with the TCR complex is CD3. See ¶¶ 0021, 0063 and 0077-0081.
Bramson teaches the domain that binds the TCR complex is the UCHT1 antibody. See ¶¶ 0023, 0063, and 0081.
Bramson teaches the cytosolic domain is a CD4 cytosolic domain and the transmembrane domain is a CD4 transmembrane domain. See ¶¶ 0025 and 0165 and Figs. 1 A-B and 5.
Bramson teaches a pharmaceutical composition comprising the T cell and a pharmaceutically acceptable carrier. See ¶¶ 0014 and 0131-0133.
Bramson teaches as set forth above, but does not teach a Chimeric Costimulatory Receptor (CCR) polypeptide comprising: (i) a first polypeptide comprising an extracellular domain of a member of the Tumor Necrosis Factor Receptor Superfamily (TNFRSF) that binds tumor necrosis alpha (TNFa); (ii) a second polypeptide comprising a transmembrane domain polypeptide; and (iii) a third polypeptide comprising a cytosolic costimulatory signaling domain polypeptide.
Cobbold teaches that the invention is drawn to genetic modification of immune cells to enhance their function for therapy or diagnosis. See abstract and ¶¶ 0010-0012.
Cobbold teaches that an enhanced signaling receptor (ESR), TNFR1/4-1BB (SEQ ID NO: 302), comprising the TNFR1A extracellular and transmembrane domains and the intracellular domains from 4-1BB provides T cells with a growth, proliferation and/or survival advantage. See ¶¶ 00168, 00203-00204 and Table 9.
SEQ ID NO: 302 of Cobbold comprises the TNFR1 extracellular domain of SEQ ID NO: 1. See Appendix.
SEQ ID NO: 302 of Cobbold comprises the 4-1BB domain SEQ ID NO: 3. See Appendix.
SEQ ID NO: 302 of Cobbold comprises the TNFR1 transmembrane domain of SEQ ID NO: 5. See Appendix.
SEQ ID NO: 302 of Cobbold is 99.3% identical to the CCR of SEQ ID NO: 7. See Appendix.
Regarding claims 235 and 236, Cobbold teaches that the transmembrane and intracellular domain of 4-BB can also be used in an enhanced signaling receptor (ESR). See ¶¶ 00110, 00111, and 00212.
Regarding claim 237, Bramson teaches using linkers for joining protein domains. See ¶¶ 0092-0093, 0099 and 0101.
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 Bramson and Cobbold and engineer the T cells expressing the trifunctional T cell-antigen coupler of Bramson to also express an ESR like TNFR1/4-1BB (SEQ ID NO: 302) CCR of Cobbold because Cobbold teaches that the TNFR1/4-1BB (SEQ ID NO: 302) provides T cells with a growth, proliferation and/or survival advantage. Thus, one would have motivated to also express TNFR1/4-1BB (SEQ ID NO: 302) of Cobbold in the T cells expressing the trifunctional T cell-antigen coupler of Bramson to provide a growth, proliferation and/or survival advantage to the T cells for enhancing production and therapy with the T cells.
Additionally, 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 Bramson and Cobbold and use linkers taught by Bramson in a CCR construct like TNFR1/4-1BB (SEQ ID NO: 302) of Cobbold to provide flexibility between the various domains of the protein and optimize its activity.
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.
9a. Claims 227-245 are rejected on the ground of nonstatutory double patenting as being unpatentable over the claims of the U.S. Patents set forth below in view of US 2016/0368964 A1 (Bramson et al. Dec. 22, 2016), “Bramson” in view of WO 2020/163755 A9 (Cobbold et al. Aug. 13, 2020, filed Feb. 7, 2020), “Cobbold”.
9b. Claims 227-245 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims of the co-pending Application Nos set forth below in view of US 2016/0368964 A1 (Bramson et al. Dec. 22, 2016), “Bramson” in view of WO 2020/163755 A9 (Cobbold et al. Aug. 13, 2020, filed Feb. 7, 2020), “Cobbold”.
This is a provisional nonstatutory double patenting rejection.
No.
Patent No. or Application No.
Claims
1
US 10,435,453 B2
1-29
2
US 11,421,014 B2
1-9
3
US 11,008,376 B2
1-12
4
US 11,001,621 B1
1-18
5
17/808,361, published as US 2022/0332790 A1
37-56
6
US 10,640,562 B2
1-18
7
US 11,111,298 B2
1-11
8
US 11,976,117 B2
1-8
9
US 11,198,737 B2
1-13
10
US 11,643,472 B2
1-9
11
US 11,970,545 B2
1-19
12
US 11,110,123 B2
1-11
13
US 11,406,667 B2
1-6
14
US 11,878,035 B2
1-6
15
17/810,326 published as US 2022/0331364
108-116
16
11,453,723 B1
1-15
The patented and co-pending claims are drawn to T cell Antigen Coupler proteins, nucleic acids and T-cells comprising the TACs which target antigens like BCMA, Her-2 and CD19.
The patented and co-pending claims as set forth above, but do not teach a Chimeric Costimulatory Receptor (CCR) polypeptide comprising: (i) a first polypeptide comprising an extracellular domain of a member of the Tumor Necrosis Factor Receptor Superfamily (TNFRSF) that binds tumor necrosis alpha (TNFa); (ii) a second polypeptide comprising a transmembrane domain polypeptide; and (iii) a third polypeptide comprising a cytosolic costimulatory signaling domain polypeptide.
Bramson and Cobbold teach as set forth above.
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 the patented or co-pending claims, Bramson and Cobbold and engineer T cells expressing the T cell Antigen Couplers of the patented or co-pending claims to also express an ESR like TNFR1/4-1BB (SEQ ID NO: 302) CCR of Cobbold because Cobbold teaches that the TNFR1/4-1BB (SEQ ID NO: 302) provides T cells with a growth, proliferation and/or survival advantage. Thus, one would have motivated to also express TNFR1/4-1BB (SEQ ID NO: 302) of Cobbold in the T cells expressing the T cell Antigen Couplers of the patented or co-pending claims to provide a growth, proliferation and/or survival advantage to the T cells for enhancing production and therapy with the T cells.
Additionally, 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 patented or co-pending claim, Bramson and Cobbold and use linkers of Bramson in a CCR construct like TNFR1/4-1BB (SEQ ID NO: 302) of Cobbold to provide flexibility between the various domains of the protein and optimize its activity.
Conclusion
10. No claims allowed.
11. 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: 1 with SEQ ID NO: 302 of Cobbold
US-17-429-342-302
Query Match 100.0%; Score 1187; DB 1; Length 276;
Best Local Similarity 100.0%;
Matches 210; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GLSTVPDLLLPLVLLELLVGIYPSGVIGLVPHLGDREKRDSVCPQGKYIHPQNNSICCTK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2 GLSTVPDLLLPLVLLELLVGIYPSGVIGLVPHLGDREKRDSVCPQGKYIHPQNNSICCTK 61
Qy 61 CHKGTYLYNDCPGPGQDTDCRECESGSFTASENHLRHCLSCSKCRKEMGQVEISSCTVDR 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 62 CHKGTYLYNDCPGPGQDTDCRECESGSFTASENHLRHCLSCSKCRKEMGQVEISSCTVDR 121
Qy 121 DTVCGCRKNQYRHYWSENLFQCFNCSLCLNGTVHLSCQEKQNTVCTCHAGFFLRENECVS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122 DTVCGCRKNQYRHYWSENLFQCFNCSLCLNGTVHLSCQEKQNTVCTCHAGFFLRENECVS 181
Qy 181 CSNCKKSLECTKLCLPQIENVKGTEDSGTT 210
||||||||||||||||||||||||||||||
Db 182 CSNCKKSLECTKLCLPQIENVKGTEDSGTT 211
Alignment of SEQ ID NO: 3 with SEQ ID NO: 302 of Cobbold
US-17-429-342-302
Query Match 100.0%; Score 232; DB 1; Length 276;
Best Local Similarity 100.0%;
Matches 42; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL 42
||||||||||||||||||||||||||||||||||||||||||
Db 235 KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL 276
Alignment of SEQ ID NO: 5 with SEQ ID NO: 302 of Cobbold
US-17-429-342-302
Query Match 100.0%; Score 102; DB 1; Length 276;
Best Local Similarity 100.0%;
Matches 21; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 VLLPLVIFFGLCLLSLLFIGL 21
|||||||||||||||||||||
Db 212 VLLPLVIFFGLCLLSLLFIGL 232
Alignment of SEQ ID NO: 7 with SEQ ID NO: 302 of Cobbold
US-17-429-342-302
Query Match 99.3%; Score 1510; DB 1; Length 276;
Best Local Similarity 99.3%;
Matches 273; Conservative 0; Mismatches 0; Indels 2; Gaps 1;
Qy 1 GLSTVPDLLLPLVLLELLVGIYPSGVIGLVPHLGDREKRDSVCPQGKYIHPQNNSICCTK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 2 GLSTVPDLLLPLVLLELLVGIYPSGVIGLVPHLGDREKRDSVCPQGKYIHPQNNSICCTK 61
Qy 61 CHKGTYLYNDCPGPGQDTDCRECESGSFTASENHLRHCLSCSKCRKEMGQVEISSCTVDR 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 62 CHKGTYLYNDCPGPGQDTDCRECESGSFTASENHLRHCLSCSKCRKEMGQVEISSCTVDR 121
Qy 121 DTVCGCRKNQYRHYWSENLFQCFNCSLCLNGTVHLSCQEKQNTVCTCHAGFFLRENECVS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 122 DTVCGCRKNQYRHYWSENLFQCFNCSLCLNGTVHLSCQEKQNTVCTCHAGFFLRENECVS 181
Qy 181 CSNCKKSLECTKLCLPQIENVKGTEDSGTTVLLPLVIFFGLCLLSLLFIGL--KRGRKKL 238
||||||||||||||||||||||||||||||||||||||||||||||||||| |||||||
Db 182 CSNCKKSLECTKLCLPQIENVKGTEDSGTTVLLPLVIFFGLCLLSLLFIGLCVKRGRKKL 241
Qy 239 LYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL 273
|||||||||||||||||||||||||||||||||||
Db 242 LYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL 276