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 4, 18, 21, 24, 27, 30, 49 – 54, 59 – 61, 63 – 64, 76 – 82 and 94 are currently pending. Claims 4, 18, 24, 27, 30, 49 – 54, 59 – 60, 63 – 64, 76 – 82 and 94 are the subject of this Office Action. This is the first Office Action on the merits of the claims. Non-elected claims 21 and 61 are withdrawn from consideration.
Election/Restrictions
Applicant’s elections with traverse of Group I in the reply filed 03/24/2026 is acknowledged.
On page 18, third paragraph, Applicant argues that “the Office has not shown that the burden imposed on the Office in examining Groups I and II together would be serious.”
In view of the prior art, the restriction among Groups I and II is withdrawn, and claim 82 of Group II is rejoined.
In the reply, Applicant elects the species of the multispecific antibody comprising:
an anti-HER2 heavy chain fused to an anti-CD137 scFv comprising the amino acid sequence set forth in SEQ ID NO: 205; and ii) an anti-HER2 light chain comprising the amino acid sequence set forth in SEQ ID NO: 185.
The anti-CD137 scFv portion of the multispecific antibody comprises a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO: 127, with CDRs 1-3 comprising SEQ ID NOs: 121, 122, and 123; and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO: 128 with CDRs 1-3 comprising SEQ ID NOs: 124, 125, and 126.
The anti-HER2 portion of the multispecific antibody comprises a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO: 202, with CDRs 1-3 comprising SEQ ID NOs: 186, 190, and 194; and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO: 203 with CDRs 1-3 comprising SEQ ID NOs: 196, 198, and 200.
Claims 4, 18, 24, 27, 30, 49 – 54, 59 – 60, 63 – 64, 76 – 82 and 94 are examined on the merits.
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 08/26/2022, 07/26/2024, and 03/31/2025 are in compliance with the provisions of 37 CFR 1.97 and have been considered.
Specification
The amendment filed on 03/24/2026 is objected to under 35 U.S.C. 132(a) because it introduces new matter into the disclosure. 35 U.S.C. 132(a) states that no amendment shall introduce new matter into the disclosure of the invention. The added material which is not supported by the original disclosure is as follows: the changes to sequences of SEQ ID NOs: 8, 18, 28, 38, 48, 58, 68, 78, 88, 98, 108, 118, 128, 138, 148, 238, and 248.
On p. 16, last paragraph – p. 17, first paragraph, of the reply of 03/24/2026, Applicant argues “that that the Replacement XML Sequence Listing and substitute specification submitted herewith correct an obvious error, which would be recognized and appropriately corrected by a person of skill in the art. Specifically, Applicant submits that a person of skill in the art would recognize i) that SEQ ID NOs: 8, 18, 28, 38, 48, 58, 68, 78, 88, 98, 108, 118, 128, 138, 148, 238, and 248 are light chain variable region ("VL") sequences, and ii) that "RTV" does not belong at the end of those light chain variable region sequences because "RTV" actually belongs at the beginning of the light chain constant region sequence. See, e.g., UniProtKB entry P01834 - IGKCHUMAN, available online at <https://www.uniprot.org/uniprotkb/PO1834/entry> and a copy of which is submitted herewith, for the standard kappa light chain constant region.”
Applicant’s argument has been fully considered. However, because of the creative nature of antibody engineering, positions of any tripeptides, even specific ones like “RTV”, in polypeptides do not necessarily have specific meanings. Although “RTV” may often be found in the beginning of VL sequences, its appearance at the C-terminal end may also be a result of deliberate recombinant engineering. Furthermore, although Applicant argues that “RTV” belongs in the beginning of the sequences of SEQ ID NOs: 8, 18, 28, 38, 48, 58, 68, 78, 88, 98, 108, 118, 128, 138, 148, 238, and 248 , none of the sequences has been amended with “RTV” in the beginning.
Thus, Applicant’s amendments of the sequences of that SEQ ID NOs: 8, 18, 28, 38, 48, 58, 68, 78, 88, 98, 108, 118, 128, 138, 148, 238, and 248 add new matter to the application. Applicant is required to cancel the new matter in the reply to this Office Action.
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.
Claim 82 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for treating a tumor, does not reasonably provide enablement for treating any other disease or preventing any disease. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Scope of Enablement
Claim 82 is rejected under 35 U.S.C. 112(a) because the claim is directed to a method of treating or preventing a disease in a subject, comprising administering to the subject an effective amount of the pharmaceutical composition comprising the multispecific antibody that binds to CD137 and HER2. However, neither the specification nor the prior art teaches such a method of treating or preventing a disease in a subject. HER2 is a protein overexpressed on the certain types of cancer cells. Thus, targeting this receptor would be expected to treat cancer. Targeting CD137 would be expected to promote a T-cell immune response (which would help with the cancer treatment). However, this would have no effect on, for example, genetic disorders, disorders that do not involve CD137/HER2 targets including fighting bacterial infections, viral infections (common flu), neurodegenerative conditions which proceed by completely different mechanism, etc.
In this regard, the application disclosure and claims have been compared per the factors indicated in the decision In re Wands, 8 USPQ 2d 1400 (Fed. Cir., 1988) as to undue experimentation. The factors include:
1) the nature of the invention;2) the scope or breadth of the claims;3) the state of the prior art;4) the predictability or unpredictability of the art; 5) the relative skill of those skilled in the art; 6) the presence or absence of working examples; 7) the amount of direction or guidance presented and,8) the quantity of experimentation necessary.
The relevant factors are addressed below on the basis of comparison of the disclosure, the claims and the state of the prior art in the assessment of undue experimentation.
Scope or breadth of the claims: Present claim 82 recites a method of treating or preventing a disease in a subject, comprising administering to the subject an effective amount of the pharmaceutical composition of claim 77. Present claim 77 recites a pharmaceutical composition comprising the multispecific antibody of claim 4, and a pharmaceutically acceptable carrier. Present claim 4 recites a multispecific antibody that binds to CD137 and HER2, comprising a first antibody moiety that binds to CD137 and a second antibody moiety that binds to HER2 . . .
Degree of predictability or unpredictability in the art: The prior art teaches the targeting of CD137 and HER2 in the treatment of cancer. However, neither the prior art nor the specification teaches the treatment of diseases other than cancer with a multispecific antibody that binds CD137 and HER2. In addition, the prior art teaches that the treatment of cancer is highly complex and unpredictable. According to CLAUS (WO 2019/175125 A1, published 09/19/2019; see PTO-892: Notice of References Cited and double patenting rejection below), “[d]espite advances in treatment options, prognosis of patients with advanced cancer remains poor. Consequently, there is a persisting and urgent medical need for optimal therapies to increase survival of cancer patients without causing unacceptable toxicity. Recent results from clinical trials have shown that immune therapies can extend the overall survival of cancer patients and lead to durable responses. Despite these promising results, current immune-based therapies are only effective in a proportion of patients and combination strategies are needed to improve therapeutic benefit.” See CLAUS at Background, first paragraph, p. 1.
In addition, BRUNS (WO 2020/043683 A1, filed 08/27/2019, published 03/05/2020; see PTO-892 and double patenting rejection below) teaches that “[t]he potential of CD137 costimulation in cancer therapy has been demonstrated in many preclinical studies - the administration of agonist anti-CD137 antibodies have been shown to achieve tumor regression and the resulting CD137 signaling to break and reverse the anergy in cytotoxic T lymphocytes. Clinical trials of two agonist antibodies, urelumab and utomilumab, are ongoing, but both present significant challenges as urelumab has substantial toxicity at doses above 1 mg/kg, while utomilumab is less potent and has potential efficacy challenges. In addition, since the expression of CD137 is not limited to tumor infiltrating lymphocytes, urelumab or utomilumab monotherapy may not be capable of restricting CD137 agonism to a tumor microenvironment and thus may lead to CD137 clustering and activation in a non-localized manner. Therefore, there remains a need for anti-CD137 therapies that are both safe and effective. In addition, targeting CD137 in combination with other checkpoint immunotherapies or tumor-targeted therapies are being evaluated, but combining such therapies can augment the risk of undesired side effects, including increased systemic immune activation.” See BRUNS at paragraph 0002.
Thus, the level of unpredictability in the art is high, with the results of targeting CD137 and/or HER2 not entirely clear. A method of treating or preventing an undefined disease in a subject by administering the pharmaceutical composition of a multispecific antibody that binds to CD137 and HER2 recited in claim 82 will yield unpredictable results or may yield no results.
Relative skill possessed by those in the art: In view of the state and complexity of the prior art, and the scope of the claims, which are drawn to a method of treating or preventing a disease in a subject, comprising administering to the subject an effective amount of the pharmaceutical composition of a multispecific antibody that binds to CD137 and HER2, the level of skill in the art is high and is at least that of a medical doctor or Ph.D. scientist with several years of experience in the field of medicine.
Presence or absence of working examples: The present specification provides an example of LoVo/PBMC xenograft model mice treated with the anti-CD137×HER2 bispecific antibody (HCC) which showed a 52.5% tumor growth inhibition (TGI) (p. 139, lines 5 – 8 and 18 - 21). The specification does not provide examples of treating or preventing any other diseases in a subject or preventing tumors.
Amount of guidance or direction provided/Quantity of experimentation required: The specification only provides guidance regarding the effects of the claimed multispecific antibody that binds to CD137 and HER2 on LoVo/PBMC xenograft model mice.
In the absence of working examples, undue experimentation would be necessary to determine the scope of treating or preventing any disease in a subject with the claimed multispecific antibody that binds to CD137 and HER2.
Conclusion: In summary, the claims contain subject matter which is not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
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.
Claim 27 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.
In particular, “e.g.” renders the claim indefinite because it is not clear whether the limitations following “e.g.” are part of the claimed invention. See MPEP § 2173.05(d).
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 4, 18, 24, 27, 30, 49 – 54, 59 – 60, 76 – 82 and 94 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 4, 17, 20, 23, 26 – 30, 33, 35 – 36, 38, 45, 47 – 52 and 61 of copending Application No. 17/822,710 in view of CLAUS (WO 2019/175125 A1, published 09/19/2019; see PTO-892: Notice of References Cited).
Copending claim 4 recites an isolated anti-CD137 construct comprising an anti-CD137 antibody moiety comprising a heavy chain variable region (VH) that comprises HC -CDR1, HC -CDR2, and HC -CDR3 domains; and a light chain variable region (VL) that comprises LC -CDR1, LC -CDR2, and LC - CDR3 domains; and copending claim 23 recites that the isolated anti-CD137 construct of claim 4, comprising an anti-CD137 antibody moiety comprising: . . . (m) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO: 127; and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO: 128; . . .
Copending claim 23 recites light a chain variable region comprising amino acids having the sequence set forth in SEQ ID NO: 218; or . . . and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO: 228.
Copending SEQ ID NO: 127 and copending SEQ ID NO: 128 teach Applicant’s elected species of a first antibody moiety that binds to CD137 and a second antibody moiety that binds to HER2, wherein the first antibody moiety comprises a heavy chain variable region (VH) comprising HC-CDR1, HC-CDR2 and HC-CDR3 domains and a light chain variable region (VL) comprising LC-CDR1, LC-CDR2 and LC-CDR3 domains and that are m) the VH comprises the HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 121, the HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 122, and the HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 123, and the VL comprises the LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 124, the LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 125, and the LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 126 of present claim 4 and 18.
Copending SEQ ID NO: 127 teaches the present CDRs having the amino acid sequences of SEQ ID NOs: 121 – 123 with 100% identity and is identical to present SEQ ID NO: 127. See Appendix.
Copending SEQ ID NO: 128, 218 and 228 each teaches the present CDRs having the amino acid sequences of SEQ ID NOs: 124 – 126 with 100% identity and is identical to present SEQ ID NO: 128. See Appendix.
Thus, the copending claims teach the first antibody moiety that binds to CD137 of the claimed multispecific antibody of present claims 4, 18 and 24.
However the copending claims do not teach the second antibody moiety which comprises a full-length antibody that binds to HER2 and comprises a second heavy chain variable region (VH-2) and a second light chain variable region (VL-2), wherein: a) the VH-2 comprises an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 186, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 190, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 194; and b) the VL-2 comprises an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 196, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 198, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 200 of present claim 4.
CLAUS is directed to a 4-1BB (CD137) agonist for use in a method for treating or delaying progression of cancer, wherein the 4-1BB (CD137) agonist is used in combination with a HER-2 targeting agent. See CLAUS at claim 1. CLAUS teaches that the combination therapy is more effective in inhibiting tumor growth and eliminating tumor cells than treatment with the 4-1BB agonists or known HER-2 targeting therapies alone. See CLAUS at p. 4, lines 32 – 34. Furthermore, CLAUS teaches a HER-2 bispecific antibody. See CLAUS at claim 2.
CLAUS teaches the second antibody moiety of present claim 4 which comprises a full-length antibody that binds to HER2 and comprises a second heavy chain variable region (VH-2) and a second light chain variable region (VL-2), wherein: a) the VH-2 comprises an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 186, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 190, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 194; and b) the VL-2 comprises an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 196, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 198, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 200.
CLAUS’ SEQ ID NO: 96 teaches the CDRs of SEQ ID NOs: 186, 190 and 194 and the VH of SEQ ID NO: 202 with 100% identity. See Appendix.
CLAUS’ SEQ ID NO: 97 teaches the CDRs of SEQ ID NOs: 196, 198 and 200 and the VL of SEQ ID NO: 203 with 100% identity. See Appendix.
At the effective filing date of the present claims, it would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the copending claims and CLAUS. The artisan would have been motivated to make and use the multispecific antibody of claims 4, 18 and 24 because the copending claims teach an anti-CD137 antibody for treating a disease and CLAUS teaches that the combination is more effective in inhibiting tumor growth and eliminating tumor cells than treatment with the 4-1BB (CD137) agonists or known HER-2 targeting therapies alone. The artisan would have a reasonable expectation of success because the copending claims and CLAUS have successfully reduced the antibodies to practice.
Regarding claim 27, copending claim 26 recites that the construct comprises an antibody or antigen-binding fragment thereof selected from the group consisting of a full-length antibody, a multispecific antibody (e.g., a bispecific antibody), a single-chain Fv (scFv), a Fab fragment, a Fab' fragment, a F(ab')2, an Fv fragment, a disulfide stabilized Fv fragment (dsFv), a (dsFv)2, a VHH, a Fv-Fc fusion, a scFv-Fc fusion, a scFv-Fv fusion, a diabody, a tribody, and a tetrabody.
Regarding claim 30, copending claim 29 teaches that the anti-CD137 antibody moiety is a CD137 agonist antibody.
Regarding claims 49 – 50 and 52 – 53, CLAUS teaches that the Fc region variant may comprise a human Fc region sequence (e.g., a human IgGl, IgG2, IgG3 or IgG4 Fc region). See CLAUS at p. 47, lines 30 – 33.
Regarding claim 51, CLAUS teaches that the antibody according to the invention which comprises an Fe domain with the amino acid substitutions L234A, L235A. See CLAUS at p. 48, lines 7 – 9.
Regarding claim 54, CLAUS teaches that IgG4 Fc domain comprising an amino acid substitution at position S228 (Kabat numbering), particularly the amino acid substitution S228P. See CLAUS at p. 48, lines 23 – 25.
Regarding claim 59, CLAUS teaches the sequences of present SEQ ID NOs: 202 and 203. CLAUS’ SEQ ID NO: 96 teaches the sequence of present SEQ ID NO: 202 with 100% identity, and CLAUS’ SEQ ID NO: 97 teaches the sequence of present SEQ ID NO: 203 without the C-terminal R. See Appendix.
Regarding claim 60, the copending claims teaches the claimed first antibody moiety, and CLAUS teaches the claimed second antibody moiety as discussed above.
Regarding claim 76, CLAUS teaches that a DNA encoding a short protein sequence that could be used to facilitate later purification (e.g. a histidine tag) or assist in labeling the fusion protein may be included within or at the ends of the polynucleotide encoding the disclosed antibody or polypeptide fragments thereof. See CLAUS at p. 56, lines 13 – 16. CLAUS further teaches the binding of the disclosed antibody may be measured via radioimmunassay (p. 24, lines 20 – 22), and thus CLAUS teaches the use of a radioisotope on the antibody.
Regarding claim 77, copending claim 47 recites a pharmaceutical composition comprising the isolated anti-CD137 construct and a pharmaceutically acceptable carrier.
Regarding claim 78, copending claim 48 recites an isolated nucleic acid encoding the anti-CD137 construct.
Regarding claim claim 79, copending claim 49 recites a vector comprising the isolated nucleic acid.
Regarding claim 80, copending claim 50 recites an isolated host cell comprising the isolated nucleic acid.
Regarding claim 81, copending claim 51 recites a method of producing an anti-CD137 construct, comprising: a) culturing the isolated host cell of claim 50 under conditions effective to express the anti-CD137 construct; and b) obtaining the expressed anti-CD137 construct from the host cell.
Regarding claim 82, copending claim 52 recites a method of treating or preventing a disease in an individual, comprising administering to the individual an effective amount of
Regarding claim 94, copending claim 61 recites a kit comprising the anti-CD137 construct.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 4, 18, 24, 27, 30, 49 – 54, 59 – 60, 63 – 64, 76 – 82 and 94 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 18, 21, 24, 27, 30, 74, 50 – 54, 60, 64 – 66, 68 – 69, 84, 86 – 91 and 102 of copending Application No. 17/822,737 in view of BRUNS (WO 2020/043683 A1, filed 08/27/2019, published 03/05/2020; see PTO-892).
Copending claim 1 recites a multispecific antibody that binds to human CD137 and human EGFR, comprising a first antibody moiety that binds to human CD137 and a second antibody moiety that binds to human EGFR, wherein the first antibody moiety comprises a heavy chain variable region (VH) ...
Copending claim 24 recites (m) a heavy chain variable region comprising amino acids having the sequence set forth in SEQ ID NO: 127 and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO: 128 . . . a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO: 268; or . . . and a light chain variable region comprising amino acids having the sequence set forth in SEQ ID NO: 278.
Copending claim recites an anti-human CD137 single chain Fv fragment which comprises an amino acid sequence having at least about 90% sequence identity to the amino acid sequence of any one of SEQ ID NOs: 183, 185, 188, 189, 230, 231, 259, 260, 281 or 282.
Copending SEQ ID NOs: 127, 183, 185, 188, 189, 230 and 231 each teaches the VH comprises the HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 121, the HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 122, and the HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 123 of present claims 4 and 18 with 100% identity. See Appendix.
Copending SEQ ID NOs: 128, 268, 278, 183, 185, 188, 230, 231, 259, 260, 282 each teaches the VL comprises the LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 124, the LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 125, and the LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 126 of present claim 4 and 18 with 100% identity. See Appendix.
Copending SEQ ID NO: 127 is identical to present SEQ ID NO: 127 of present claim 24. See Appendix.
Copending SEQ ID NO: 128 is identical to present SEQ ID NO: 128 of present claim 24. See Appendix.
Thus, the copending claims teach the first antibody moiety that binds to CD137 of the claimed multispecific antibody of present claims 4, 18 and 24.
However the copending claims do not teach the second antibody moiety which comprises a full-length antibody that binds to HER2 and comprises a second heavy chain variable region (VH-2) and a second light chain variable region (VL-2), wherein: a) the VH-2 comprises an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 186, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 190, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 194; and b) the VL-2 comprises an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 196, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 198, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 200 of present claim 4.
BRUNS is directed to a method of treating cancer in a subject, comprising administering to the subject: (a) a CD137/HER2 bispecific agent. See BRUNS at claim 1. BRUNS teaches compositions and methods for enhancing immune response in an individual having HER2-positive advanced or metastatic solid tumors. See BRUNS at the abstract.
BRUNS teaches the second antibody moiety which comprises a full-length antibody that binds to HER2 and comprises a second heavy chain variable region (VH-2) and a second light chain variable region (VL-2), wherein: a) the VH-2 comprises an HC-CDR1 comprising the amino acid sequence of SEQ ID NO: 186, an HC-CDR2 comprising the amino acid sequence of SEQ ID NO: 190, and an HC-CDR3 comprising the amino acid sequence of SEQ ID NO: 194; and b) the VL-2 comprises an LC-CDR1 comprising the amino acid sequence of SEQ ID NO: 196, an LC-CDR2 comprising the amino acid sequence of SEQ ID NO: 198, and an LC-CDR3 comprising the amino acid sequence of SEQ ID NO: 200 of present claim 4. See below and Appendix.
BRUNS also teaches Applicant’s elected sequence of SEQ ID NOs: 202 and 203 of present claim 59 and SEQ ID NO: 185 of present claims 63 – 64, all with 100% identity. See below and Appendix.
BRUNS’ SEQ ID NO: 64 teaches the CDRs of SEQ ID NOs: 186, 190 and 194 of present claim 4 and teaches the sequence of SEQ ID NO: 202 of present claim 59 with 100% identity. See Appendix.
BRUNS’ SEQ ID NO: 65 teaches the CDRs of SEQ ID NOs: 196, 198 and 200 of present claim 4 and teaches the sequence of SEQ ID NO: 203 of present claim 59 with 100% identity. See Appendix.
At the effective filing date of the present claims, it would have been prima facie obvious to the person of ordinary skill in the art to arrive at the claimed invention from the disclosures of the copending claims and BRUNS. The artisan would have been motivated to make and use the multispecific antibody of the present claims because the copending claims teach an anti-CD137 antibody for treating a tumor (copending claim 91) and BRUNS teaches a CD137/HER2 bispecific agent for enhancing immune response in an individual having HER2-positive advanced or metastatic solid tumors. The artisan would have a reasonable expectation of success because the copending claims and BRUNS have successfully reduced the antibodies to practice.
Regarding claim 27, copending claim 27 recites that the first antibody moiety comprises an antibody or antigen-binding fragment thereof selected from the group consisting of a full-length antibody, a single-chain Fv (scFv), a Fab fragment, a Fab' fragment, a F(ab')2, an Fv fragment, a disulfide stabilized Fv fragment (dsFv), a (dsFv)2, a VHH, a Fv-Fc fusion, and a scFv-Fc fusion.
Regarding claim 30, copending claim 30 teaches that the anti-CD137 antibody moiety is a CD137 agonist antibody.
Regarding claims 49 – 54, copending claims 47 and 50 – 54 recites these limitations, respectively.
Regarding claim 60, the copending claims teaches the claimed first antibody moiety, and BRUNS teaches the claimed second antibody moiety as discussed above.
Regarding claims 63 – 64, the copending claims and BRUNS teaches the sequences of Applicant’s elected species of SEQ ID NOs: 205 and 185. Copending SEQ ID NOs: 188, 231, 260, 282, 189 and 259 of copending claim 68 each teaches the sequence of present SEQ ID NO: 205 with at least 90% identity (see Appendix), and BRUNS’ SEQ ID NO: 80 is identical to the sequence of present SEQ ID NO: 185 (see Appendix).
Regarding claim 76, copending claim 84 recites an immunoconjugate comprising the multispecific antibody of claim 1, linked to a therapeutic agent or a label.
Regarding claim 77, copending claim 86 recites a pharmaceutical composition comprising the isolated anti-CD137 construct and a pharmaceutically acceptable carrier.
Regarding claims 78 - 81, copending claims 87 - 90 recites the limitations of these present claims, respectively.
Regarding claim 82, copending claim 91 recites a method of treating a tumor in a subject, comprising administering to the subject an effective amount of the multispecific antibody, wherein the tumor is a colon cancer tumor or an epidermoid cancer tumor.
Regarding claim 94, copending claim 102 recites a kit comprising the multispecific antibody.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Estella Gustilo whose telephone number is (703)756-1706. The examiner can normally be reached Monday - Friday 9:30 AM - 5:30 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, Gregory Emch can be reached at 571-272-8149. 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
/GREGORY S EMCH/Supervisory Patent Examiner, Art Unit 1678
APPENDIX
Alignment of SEQ ID NOs: 121 – 123 (anti-CD137 VH CDRs):
US-17-822-710-127
(NOTE: this sequence has 3 duplicates in the database searched.
See complete list at the end of this report)
Sequence 127, US/17822710
Publication No. US20240076395A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: ANTI-CD137 CONSTRUCTS AND USES THEREOF (en)
FILE REFERENCE: HLX25
CURRENT APPLICATION NUMBER: US/17/822,710
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 230
SEQ ID NO 127
LENGTH: 119
TYPE: PRT
FEATURE:
NAME/KEY: DOMAIN
LOCATION: 1..119
QUALIFIERS: note = Clone 2-9 VH
FEATURE:
NAME/KEY: source
LOCATION: 1..119
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 86.2%; Score 153.4; Length 119;
Best Local Similarity 41.0%;
Matches 32; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 DTYIH--------------RIDPANGNSEYAQKFQG------------------------ 22
||||| |||||||||||||||||
Db 31 DTYIHWVRQAPGQGLEWMGRIDPANGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSED 90
Qy 23 --------GNLHYALMDY 32
||||||||||
Db 91 TAVYYCTTGNLHYALMDY 108
US-17-822-737-183
Sequence 183, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 183
LENGTH: 706
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..706
QUALIFIERS: note = Anti-EGFR HC-anti-CD137 scFv-IgG1-Linker 7 (HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..706
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 86.2%; Score 153.4; Length 706;
Best Local Similarity 41.0%;
Matches 32; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 DTYIH--------------RIDPANGNSEYAQKFQG------------------------ 22
||||| |||||||||||||||||
Db 618 DTYIHWVRQAPGQGLEWMGRIDPANGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSED 677
Qy 23 --------GNLHYALMDY 32
||||||||||
Db 678 TAVYYCTTGNLHYALMDY 695
US-17-822-737-185
Sequence 185, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 185
LENGTH: 706
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..706
QUALIFIERS: note = Anti-EGFR -HC-anti-CD137 scFv-IgG1-LALA-Linker 7
(HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..706
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 86.2%; Score 153.4; Length 706;
Best Local Similarity 41.0%;
Matches 32; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 DTYIH--------------RIDPANGNSEYAQKFQG------------------------ 22
||||| |||||||||||||||||
Db 618 DTYIHWVRQAPGQGLEWMGRIDPANGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSED 677
Qy 23 --------GNLHYALMDY 32
||||||||||
Db 678 TAVYYCTTGNLHYALMDY 695
US-17-822-737-188
Sequence 188, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 188
LENGTH: 726
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..726
QUALIFIERS: note = Anti-EGFR HC-anti-CD137 scFv-IgG1-LALA- Positive
Charge Linker(HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..726
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 86.2%; Score 153.4; Length 726;
Best Local Similarity 41.0%;
Matches 32; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 DTYIH--------------RIDPANGNSEYAQKFQG------------------------ 22
||||| |||||||||||||||||
Db 638 DTYIHWVRQAPGQGLEWMGRIDPANGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSED 697
Qy 23 --------GNLHYALMDY 32
||||||||||
Db 698 TAVYYCTTGNLHYALMDY 715
US-17-822-737-189
Sequence 189, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 189
LENGTH: 726
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..726
QUALIFIERS: note = Anti-EGFR HC-anti-CD137 scFv-IgG1-LALA-Negative
Charge Linker(HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..726
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 86.2%; Score 153.4; Length 726;
Best Local Similarity 41.0%;
Matches 32; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 DTYIH--------------RIDPANGNSEYAQKFQG------------------------ 22
||||| |||||||||||||||||
Db 638 DTYIHWVRQAPGQGLEWMGRIDPANGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSED 697
Qy 23 --------GNLHYALMDY 32
||||||||||
Db 698 TAVYYCTTGNLHYALMDY 715
US-17-822-737-230
Sequence 230, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 230
LENGTH: 699
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..699
QUALIFIERS: note = Anti-EGFR HC-anti-CD137 scFv-IgG1 LALA-Linker 10(HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..699
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 86.2%; Score 153.4; Length 699;
Best Local Similarity 41.0%;
Matches 32; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 DTYIH--------------RIDPANGNSEYAQKFQG------------------------ 22
||||| |||||||||||||||||
Db 611 DTYIHWVRQAPGQGLEWMGRIDPANGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSED 670
Qy 23 --------GNLHYALMDY 32
||||||||||
Db 671 TAVYYCTTGNLHYALMDY 688
US-17-822-737-231
Sequence 231, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 231
LENGTH: 726
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..726
QUALIFIERS: note = Anti-EGFR HC-anti-CD137 scFv-IgG1-LALA- Positive
Charge Linker(HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..726
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 86.2%; Score 153.4; Length 726;
Best Local Similarity 41.0%;
Matches 32; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 DTYIH--------------RIDPANGNSEYAQKFQG------------------------ 22
||||| |||||||||||||||||
Db 638 DTYIHWVRQAPGQGLEWMGRIDPANGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSED 697
Qy 23 --------GNLHYALMDY 32
||||||||||
Db 698 TAVYYCTTGNLHYALMDY 715
Alignment of SEQ ID NO: 127 (ant-CD137 VH)
US-17-822-710-127
(NOTE: this sequence has 3 duplicates in the database searched.
See complete list at the end of this report)
Sequence 127, US/17822710
Publication No. US20240076395A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: ANTI-CD137 CONSTRUCTS AND USES THEREOF (en)
FILE REFERENCE: HLX25
CURRENT APPLICATION NUMBER: US/17/822,710
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 230
SEQ ID NO 127
LENGTH: 119
TYPE: PRT
FEATURE:
NAME/KEY: DOMAIN
LOCATION: 1..119
QUALIFIERS: note = Clone 2-9 VH
FEATURE:
NAME/KEY: source
LOCATION: 1..119
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 100.0%; Score 628; Length 119;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKASCKASGFNIQDTYIHWVRQAPGQGLEWMGRIDPANGNSEY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKASCKASGFNIQDTYIHWVRQAPGQGLEWMGRIDPANGNSEY 60
Qy 61 AQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTGNLHYALMDYWGQGTSVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTGNLHYALMDYWGQGTSVTVSS 119
US-17-822-737-127
Filing date in PALM: 2022-08-26
Sequence 127, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 127
LENGTH: 119
TYPE: PRT
FEATURE:
NAME/KEY: DOMAIN
LOCATION: 1..119
QUALIFIERS: note = Clone 2-9 VH
FEATURE:
NAME/KEY: source
LOCATION: 1..119
QUALIFIERS: mol_type = protein
organism = synthetic construct
ALIGNMENT:
Query Match 100.0%; Score 628; Length 119;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKASCKASGFNIQDTYIHWVRQAPGQGLEWMGRIDPANGNSEY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKASCKASGFNIQDTYIHWVRQAPGQGLEWMGRIDPANGNSEY 60
Qy 61 AQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTGNLHYALMDYWGQGTSVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTGNLHYALMDYWGQGTSVTVSS 119
Alignment of SEQ ID NOs: 124 – 126 (anti-CD137 VL CDRs):
US-17-822-710-128
(NOTE: this sequence has 11 duplicates in the database searched.
See complete list at the end of this report)
Sequence 128, US/17822710
Publication No. US20240076395A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: ANTI-CD137 CONSTRUCTS AND USES THEREOF (en)
FILE REFERENCE: HLX25
CURRENT APPLICATION NUMBER: US/17/822,710
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 230
SEQ ID NO 128
LENGTH: 110
TYPE: PRT
FEATURE:
NAME/KEY: DOMAIN
LOCATION: 1..110
QUALIFIERS: note = Clone 2-9 VL
FEATURE:
NAME/KEY: source
LOCATION: 1..110
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 82.5%; Score 116.3; Length 110;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 KASQPINTYLS---------------RVNRKVD--------------------------- 18
||||||||||| |||||||
Db 24 KASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTDFTLTISSLQPEDF 83
Qy 19 -----LQYLDFPYT 27
|||||||||
Db 84 ATYYCLQYLDFPYT 97
US-17-822-737-128
Filing date in PALM: 2022-08-26
Sequence 128, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 128
LENGTH: 110
TYPE: PRT
FEATURE:
NAME/KEY: DOMAIN
LOCATION: 1..110
QUALIFIERS: note = Clone 2-9 VL
FEATURE:
NAME/KEY: source
LOCATION: 1..110
QUALIFIERS: mol_type = protein
organism = synthetic construct
ALIGNMENT:
Query Match 82.5%; Score 116.3; Length 110;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 KASQPINTYLS---------------RVNRKVD--------------------------- 18
||||||||||| |||||||
Db 24 KASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTDFTLTISSLQPEDF 83
Qy 19 -----LQYLDFPYT 27
|||||||||
Db 84 ATYYCLQYLDFPYT 97
US-17-822-737-268
Filing date in PALM: 2022-08-26
Sequence 268, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 268
LENGTH: 110
TYPE: PRT
FEATURE:
NAME/KEY: DOMAIN
LOCATION: 1..110
QUALIFIERS: note = Clone 2-9-1 VL
FEATURE:
NAME/KEY: source
LOCATION: 1..110
QUALIFIERS: mol_type = protein
organism = synthetic construct
ALIGNMENT:
Query Match 82.5%; Score 116.3; Length 110;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 KASQPINTYLS---------------RVNRKVD--------------------------- 18
||||||||||| |||||||
Db 24 KASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTDFTLTISSLQPEDF 83
Qy 19 -----LQYLDFPYT 27
|||||||||
Db 84 ATYYCLQYLDFPYT 97
US-17-822-737-278
Filing date in PALM: 2022-08-26
Sequence 278, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 278
LENGTH: 110
TYPE: PRT
FEATURE:
NAME/KEY: DOMAIN
LOCATION: 1..110
QUALIFIERS: note = Clone 2-9-2 VL
FEATURE:
NAME/KEY: source
LOCATION: 1..110
QUALIFIERS: mol_type = protein
organism = synthetic construct
ALIGNMENT:
Query Match 82.5%; Score 116.3; Length 110;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 KASQPINTYLS---------------RVNRKVD--------------------------- 18
||||||||||| |||||||
Db 24 KASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTDFTLTISSLQPEDF 83
Qy 19 -----LQYLDFPYT 27
|||||||||
Db 84 ATYYCLQYLDFPYT 97
US-17-822-737-183
Sequence 183, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 183
LENGTH: 706
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..706
QUALIFIERS: note = Anti-EGFR HC-anti-CD137 scFv-IgG1-Linker 7 (HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..706
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 82.5%; Score 116.3; Length 706;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 KASQPINTYLS---------------RVNRKVD--------------------------- 18
||||||||||| |||||||
Db 485 KASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTDFTLTISSLQPEDF 544
Qy 19 -----LQYLDFPYT 27
|||||||||
Db 545 ATYYCLQYLDFPYT 558
US-17-822-737-185
Sequence 185, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 185
LENGTH: 706
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..706
QUALIFIERS: note = Anti-EGFR -HC-anti-CD137 scFv-IgG1-LALA-Linker 7
(HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..706
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 82.5%; Score 116.3; Length 706;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 KASQPINTYLS---------------RVNRKVD--------------------------- 18
||||||||||| |||||||
Db 485 KASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTDFTLTISSLQPEDF 544
Qy 19 -----LQYLDFPYT 27
|||||||||
Db 545 ATYYCLQYLDFPYT 558
US-17-822-737-188
Sequence 188, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 188
LENGTH: 726
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..726
QUALIFIERS: note = Anti-EGFR HC-anti-CD137 scFv-IgG1-LALA- Positive
Charge Linker(HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..726
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 82.5%; Score 116.3; Length 726;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 KASQPINTYLS---------------RVNRKVD--------------------------- 18
||||||||||| |||||||
Db 493 KASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTDFTLTISSLQPEDF 552
Qy 19 -----LQYLDFPYT 27
|||||||||
Db 553 ATYYCLQYLDFPYT 566
US-17-822-737-230
Sequence 230, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 230
LENGTH: 699
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..699
QUALIFIERS: note = Anti-EGFR HC-anti-CD137 scFv-IgG1 LALA-Linker 10(HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..699
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 82.5%; Score 116.3; Length 699;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 KASQPINTYLS---------------RVNRKVD--------------------------- 18
||||||||||| |||||||
Db 478 KASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTDFTLTISSLQPEDF 537
Qy 19 -----LQYLDFPYT 27
|||||||||
Db 538 ATYYCLQYLDFPYT 551
US-17-822-737-231
Sequence 231, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 231
LENGTH: 726
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..726
QUALIFIERS: note = Anti-EGFR HC-anti-CD137 scFv-IgG1-LALA- Positive
Charge Linker(HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..726
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 82.5%; Score 116.3; Length 726;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 KASQPINTYLS---------------RVNRKVD--------------------------- 18
||||||||||| |||||||
Db 493 KASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTDFTLTISSLQPEDF 552
Qy 19 -----LQYLDFPYT 27
|||||||||
Db 553 ATYYCLQYLDFPYT 566
US-17-822-737-259
Sequence 259, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 259
LENGTH: 726
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..726
QUALIFIERS: note = Anti-EGFR HC-anti-CD137 scFv-IgG1-LALA-Negative
Charge Linker(HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..726
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 82.5%; Score 116.3; Length 726;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 KASQPINTYLS---------------RVNRKVD--------------------------- 18
||||||||||| |||||||
Db 493 KASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTDFTLTISSLQPEDF 552
Qy 19 -----LQYLDFPYT 27
|||||||||
Db 553 ATYYCLQYLDFPYT 566
US-17-822-737-260
Sequence 260, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 260
LENGTH: 726
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..726
QUALIFIERS: note = Anti-EGFR HC-anti-CD137-1 scFv-IgG1-LALA- Positive
Charge Linker(HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..726
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 82.5%; Score 116.3; Length 726;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 KASQPINTYLS---------------RVNRKVD--------------------------- 18
||||||||||| |||||||
Db 493 KASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTDFTLTISSLQPEDF 552
Qy 19 -----LQYLDFPYT 27
|||||||||
Db 553 ATYYCLQYLDFPYT 566
US-17-822-737-282
Sequence 282, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 282
LENGTH: 726
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..726
QUALIFIERS: note = Anti-EGFR HC-anti-CD137-2 scFv-IgG1-LALA- Positive
Charge Linker (HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..726
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 82.5%; Score 116.3; Length 726;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 KASQPINTYLS---------------RVNRKVD--------------------------- 18
||||||||||| |||||||
Db 493 KASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTDFTLTISSLQPEDF 552
Qy 19 -----LQYLDFPYT 27
|||||||||
Db 553 ATYYCLQYLDFPYT 566
Alignment of SEQ ID NO: 128 (anti-CD137 VL)
US-17-822-710-128
(NOTE: this sequence has 11 duplicates in the database searched.
See complete list at the end of this report)
Sequence 128, US/17822710
Publication No. US20240076395A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: ANTI-CD137 CONSTRUCTS AND USES THEREOF (en)
FILE REFERENCE: HLX25
CURRENT APPLICATION NUMBER: US/17/822,710
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 230
SEQ ID NO 128
LENGTH: 110
TYPE: PRT
FEATURE:
NAME/KEY: DOMAIN
LOCATION: 1..110
QUALIFIERS: note = Clone 2-9 VL
FEATURE:
NAME/KEY: source
LOCATION: 1..110
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 100.0%; Score 576; Length 110;
Best Local Similarity 100.0%;
Matches 110; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSVSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSVSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRTV 110
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRTV 110
US-17-822-710-218
Filing date in PALM: 2022-08-26
Sequence 218, US/17822710
Publication No. US20240076395A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: ANTI-CD137 CONSTRUCTS AND USES THEREOF (en)
FILE REFERENCE: HLX25
CURRENT APPLICATION NUMBER: US/17/822,710
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 230
SEQ ID NO 218
LENGTH: 110
TYPE: PRT
FEATURE:
NAME/KEY: DOMAIN
LOCATION: 1..110
QUALIFIERS: note = Clone 2-9-1 VL
FEATURE:
NAME/KEY: source
LOCATION: 1..110
QUALIFIERS: mol_type = protein
organism = synthetic construct
ALIGNMENT:
Query Match 100.0%; Score 576; Length 110;
Best Local Similarity 100.0%;
Matches 110; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSVSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSVSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRTV 110
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRTV 110
US-17-822-710-228
Filing date in PALM: 2022-08-26
Sequence 228, US/17822710
Publication No. US20240076395A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: ANTI-CD137 CONSTRUCTS AND USES THEREOF (en)
FILE REFERENCE: HLX25
CURRENT APPLICATION NUMBER: US/17/822,710
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 230
SEQ ID NO 228
LENGTH: 110
TYPE: PRT
FEATURE:
NAME/KEY: DOMAIN
LOCATION: 1..110
QUALIFIERS: note = Clone 2-9-2 VL
FEATURE:
NAME/KEY: source
LOCATION: 1..110
QUALIFIERS: mol_type = protein
organism = synthetic construct
ALIGNMENT:
Query Match 100.0%; Score 576; Length 110;
Best Local Similarity 100.0%;
Matches 110; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSVSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSVSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRTV 110
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRTV 110
US-17-822-737-128
Filing date in PALM: 2022-08-26
Sequence 128, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 128
LENGTH: 110
TYPE: PRT
FEATURE:
NAME/KEY: DOMAIN
LOCATION: 1..110
QUALIFIERS: note = Clone 2-9 VL
FEATURE:
NAME/KEY: source
LOCATION: 1..110
QUALIFIERS: mol_type = protein
organism = synthetic construct
ALIGNMENT:
Query Match 100.0%; Score 576; Length 110;
Best Local Similarity 100.0%;
Matches 110; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSVSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSVSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRTV 110
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRTV 110
Alignment of SEQ ID NOs: 186, 190 and 194 (anti-HER2 HCDRs):
BGU01009
ID BGU01009 standard; protein; 120 AA.
XX
AC BGU01009;
XX
DT 14-NOV-2019 (first entry)
XX
DE Humanized anti-HER-2 trastuzumab heavy chain variable region, SEQ 96.
XX
KW Erbb2 tyrosine kinase receptor; HERCEPTIN; Her2 protein;
KW antibody therapy; bladder cancer; breast tumor; cancer; colon tumor;
KW cytostatic; endometrioid carcinoma; esophagus tumor; head and neck tumor;
KW heavy chain variable region; humanized antibody; lung tumor;
KW monoclonal antibody; neoplasm; ovary tumor; pancreas tumor;
KW prophylactic to disease; prostate tumor; stomach tumor; therapeutic;
KW trastuzumab.
XX
OS Homo sapiens.
OS Mus sp.
OS Chimeric.
XX
CC PN WO2019175125-A1.
XX
CC PD 19-SEP-2019.
XX
CC PF 12-MAR-2019; 2019WO-EP056067.
XX
PR 13-MAR-2018; 2018EP-00161340.
XX
CC PA (HOFF ) HOFFMANN LA ROCHE & CO AG F.
CC PA (HOFF ) HOFFMANN LA ROCHE INC.
XX
CC PI Claus C, Ferrara Koller C, Klein C, Sam J, Umana P;
XX
DR WPI; 2019-805897/76.
XX
CC PT 4-1BB (CD137) agonist is used for treating or delaying progression of
CC PT cancer, where 4-1BB agonist is used in combination with HER-2 targeting
CC PT agent and 4-1BB agonist, which is antigen binding molecule comprising one
CC PT antigen binding domain.
XX
CC PS Disclosure; SEQ ID NO 96; 142pp; English.
XX
CC The present invention relates to a novel 4-1BB (CD137) agonist e.g.,
CC antigen binding molecule useful for treating or delaying progression of
CC cancer. The antigen binding molecule comprises heavy chain and light
CC chain variable region CDRs corresponds to SEQ ID NO: 9-14 (see BGU00922-
CC BGU00927). The invention further relates to: (1) a pharmaceutical product
CC comprises first composition comprising as active ingredient a 4-1BB
CC (CD137) agonist and a pharmaceutically acceptable carrier and second
CC composition comprising as active ingredient a HER-2 targeting agent and a
CC pharmaceutically acceptable carrier; (2) a pharmaceutical composition
CC comprises a 4-1BB agonist and a HER-2 targeting agent; (3) a method for
CC using the 4-1BB agonist and HER-2 targeting agent for preparing a
CC medicament for treating or delaying progression of a proliferative
CC disease; and (4) a method for treating or delaying progression of cancer
CC in a subject. The agonist of the invention is also used for preventing
CC cancer is chosen from breast cancer, ovarian cancer, stomach cancer,
CC gastric cancer, oesophageal cancer, lung cancer, uterine cancer, salivary
CC duct carcinoma, bladder cancer, endometrial cancer, pancreatic cancer,
CC colon cancer, prostate cancer, and/or head and neck cancer.
XX
SQ Sequence 120 AA;
ALIGNMENT:
Query Match 87.3%; Score 168.4; Length 120;
Best Local Similarity 41.8%;
Matches 33; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 DTYIH--------------RIYPTNGYTRYADSVKG------------------------ 22
||||| |||||||||||||||||
Db 31 DTYIHWVRQAPGKGLEWVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAED 90
Qy 23 --------WGGDGFYAMDY 33
|||||||||||
Db 91 TAVYYCSRWGGDGFYAMDY 109
BHL24546
ID BHL24546 standard; protein; 120 AA.
XX
AC BHL24546;
XX
DT 30-APR-2020 (first entry)
XX
DE Anti-HER2 trastuzumab heavy chain variable region, SEQ ID 64.
XX
KW CD340; ERBB2; HER2; antibody therapy; c-neu protein; cancer;
KW cluster of differentiation 340; cytostatic;
KW epidermal growth factor receptor 2; heavy chain variable region;
KW immune stimulation; metastasis; monoclonal antibody; neu; p185 protein;
KW proto-oncogene Neu; receptor tyrosine-protein kinase erbB-2; solid tumor;
KW therapeutic; trastuzumab.
XX
OS Unidentified.
XX
CC PN WO2020043683-A1.
XX
CC PD 05-MAR-2020.
XX
CC PF 27-AUG-2019; 2019WO-EP072754.
XX
PR 27-AUG-2018; 2018EP-00191041.
XX
CC PA (PIER-) PIERIS PHARM GMBH.
XX
CC PI Bruns I, Matis L, Olwill S, Jaquin T;
XX
DR WPI; 2020-19381C/023.
XX
CC PT Treating cancer in human, by administering cluster of differentiation
CC PT 137/human epidermal growth factor receptor 2 bispecific agent comprising
CC PT complementarity determining regions and programmed cell death protein 1
CC PT axis inhibitor.
XX
CC PS Claim 1; SEQ ID NO 64; 78pp; English.
XX
CC The present invention relates to a novel method for treating cancer in
CC human. The method comprises administering CD137 (4-1 BB)/epidermal growth
CC factor receptor 2, (HER2, HER2/neu, receptor tyrosine-protein kinase erbB
CC -2, cluster of differentiation 340 (CD340), proto-oncogene Neu, ERBB2, c-
CC neu, or p185) bispecific agent comprising CDRs and programmed cell death
CC protein 1 (PD-1, cluster of differentiation 279 or CD279) axis inhibitor
CC e.g., antibody. The invention further relates to: (1) a combination
CC comprising an CD137/HER2 bispecific agent antibody; and (2) a kit of part
CC comprises a pharmaceutical composition comprising the CD137/HER2
CC bispecific agent antibody and the PD-1 axis inhibitor. The method and
CC composition of the invention is also used for enhancing immune response
CC in an individual having HER2-positive advanced or metastatic solid
CC tumors.
XX
SQ Sequence 120 AA;
ALIGNMENT:
Query Match 87.3%; Score 168.4; Length 120;
Best Local Similarity 41.8%;
Matches 33; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 DTYIH--------------RIYPTNGYTRYADSVKG------------------------ 22
||||| |||||||||||||||||
Db 31 DTYIHWVRQSPGKGLEWVARIYPTNGYTRYADSVKGRFTISADTSKNTAYLQMNSLRAED 90
Qy 23 --------WGGDGFYAMDY 33
|||||||||||
Db 91 TAIYYCSRWGGDGFYAMDY 109
Alignment of SEQ ID NOs: 196, 198 and 200 (anti-HER2 LCDRs):
BGU01010
ID BGU01010 standard; protein; 107 AA.
XX
AC BGU01010;
XX
DT 14-NOV-2019 (first entry)
XX
DE Humanized anti-HER-2 trastuzumab light chain variable region, SEQ 97.
XX
KW Erbb2 tyrosine kinase receptor; HERCEPTIN; Her2 protein;
KW antibody therapy; bladder cancer; breast tumor; cancer; colon tumor;
KW cytostatic; endometrioid carcinoma; esophagus tumor; head and neck tumor;
KW humanized antibody; light chain variable region; lung tumor;
KW monoclonal antibody; neoplasm; ovary tumor; pancreas tumor;
KW prophylactic to disease; prostate tumor; stomach tumor; therapeutic;
KW trastuzumab.
XX
OS Homo sapiens.
OS Mus sp.
OS Chimeric.
XX
CC PN WO2019175125-A1.
XX
CC PD 19-SEP-2019.
XX
CC PF 12-MAR-2019; 2019WO-EP056067.
XX
PR 13-MAR-2018; 2018EP-00161340.
XX
CC PA (HOFF ) HOFFMANN LA ROCHE & CO AG F.
CC PA (HOFF ) HOFFMANN LA ROCHE INC.
XX
CC PI Claus C, Ferrara Koller C, Klein C, Sam J, Umana P;
XX
DR WPI; 2019-805897/76.
XX
CC PT 4-1BB (CD137) agonist is used for treating or delaying progression of
CC PT cancer, where 4-1BB agonist is used in combination with HER-2 targeting
CC PT agent and 4-1BB agonist, which is antigen binding molecule comprising one
CC PT antigen binding domain.
XX
CC PS Disclosure; SEQ ID NO 97; 142pp; English.
XX
CC The present invention relates to a novel 4-1BB (CD137) agonist e.g.,
CC antigen binding molecule useful for treating or delaying progression of
CC cancer. The antigen binding molecule comprises heavy chain and light
CC chain variable region CDRs corresponds to SEQ ID NO: 9-14 (see BGU00922-
CC BGU00927). The invention further relates to: (1) a pharmaceutical product
CC comprises first composition comprising as active ingredient a 4-1BB
CC (CD137) agonist and a pharmaceutically acceptable carrier annd second
CC composition comprising as active ingredient a HER-2 targeting agent and a
CC pharmaceutically acceptable carrier; (2) a pharmaceutical composition
CC comprises a 4-1BB agonist and a HER-2 targeting agent; (3) a method for
CC using the 4-1BB agonist and HER-2 targeting agent for preparing a
CC medicament for treating or delaying progression of a proliferative
CC disease; and (4) a method for treating or delaying progression of cancer
CC in a subject. The agonist of the invention is also used for preventing
CC cancer is chosen from breast cancer, ovarian cancer, stomach cancer,
CC gastric cancer, oesophageal cancer, lung cancer, uterine cancer, salivary
CC duct carcinoma, bladder cancer, endometrial cancer, pancreatic cancer,
CC colon cancer, prostate cancer, and/or head and neck cancer.
XX
SQ Sequence 107 AA;
ALIGNMENT:
Query Match 82.1%; Score 113.3; Length 107;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 RASQDVNTAVA---------------SASFLYS--------------------------- 18
||||||||||| |||||||
Db 24 RASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDF 83
Qy 19 -----QQHYTTPPT 27
|||||||||
Db 84 ATYYCQQHYTTPPT 97
BHL24547
ID BHL24547 standard; protein; 107 AA.
XX
AC BHL24547;
XX
DT 30-APR-2020 (first entry)
XX
DE Anti-HER2 trastuzumab light chain variable region, SEQ ID 65.
XX
KW CD340; ERBB2; HER2; antibody therapy; c-neu protein; cancer;
KW cluster of differentiation 340; cytostatic;
KW epidermal growth factor receptor 2; immune stimulation;
KW light chain variable region; metastasis; monoclonal antibody; neu;
KW p185 protein; proto-oncogene Neu;
KW receptor tyrosine-protein kinase erbB-2; solid tumor; therapeutic;
KW trastuzumab.
XX
OS Unidentified.
XX
CC PN WO2020043683-A1.
XX
CC PD 05-MAR-2020.
XX
CC PF 27-AUG-2019; 2019WO-EP072754.
XX
PR 27-AUG-2018; 2018EP-00191041.
XX
CC PA (PIER-) PIERIS PHARM GMBH.
XX
CC PI Bruns I, Matis L, Olwill S, Jaquin T;
XX
DR WPI; 2020-19381C/023.
XX
CC PT Treating cancer in human, by administering cluster of differentiation
CC PT 137/human epidermal growth factor receptor 2 bispecific agent comprising
CC PT complementarity determining regions and programmed cell death protein 1
CC PT axis inhibitor.
XX
CC PS Claim 1; SEQ ID NO 65; 78pp; English.
XX
CC The present invention relates to a novel method for treating cancer in
CC human. The method comprises administering CD137 (4-1 BB)/epidermal growth
CC factor receptor 2, (HER2, HER2/neu, receptor tyrosine-protein kinase erbB
CC -2, cluster of differentiation 340 (CD340), proto-oncogene Neu, ERBB2, c-
CC neu, or p185) bispecific agent comprising CDRs and programmed cell death
CC protein 1 (PD-1, cluster of differentiation 279 or CD279) axis inhibitor
CC e.g., antibody. The invention further relates to: (1) a combination
CC comprising an CD137/HER2 bispecific agent antibody; and (2) a kit of part
CC comprises a pharmaceutical composition comprising the CD137/HER2
CC bispecific agent antibody and the PD-1 axis inhibitor. The method and
CC composition of the invention is also used for enhancing immune response
CC in an individual having HER2-positive advanced or metastatic solid
CC tumors.
XX
SQ Sequence 107 AA;
ALIGNMENT:
Query Match 82.1%; Score 113.3; Length 107;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 RASQDVNTAVA---------------SASFLYS--------------------------- 18
||||||||||| |||||||
Db 24 RASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPSRFSGSRSGTDFTLTISSLQPEDF 83
Qy 19 -----QQHYTTPPT 27
|||||||||
Db 84 ATYYCQQHYTTPPT 97
Alignment of SEQ ID NO: 202 (anti-HER2 VH):
BGU01009
ID BGU01009 standard; protein; 120 AA.
XX
AC BGU01009;
XX
DT 14-NOV-2019 (first entry)
XX
DE Humanized anti-HER-2 trastuzumab heavy chain variable region, SEQ 96.
XX
KW Erbb2 tyrosine kinase receptor; HERCEPTIN; Her2 protein;
KW antibody therapy; bladder cancer; breast tumor; cancer; colon tumor;
KW cytostatic; endometrioid carcinoma; esophagus tumor; head and neck tumor;
KW heavy chain variable region; humanized antibody; lung tumor;
KW monoclonal antibody; neoplasm; ovary tumor; pancreas tumor;
KW prophylactic to disease; prostate tumor; stomach tumor; therapeutic;
KW trastuzumab.
XX
OS Homo sapiens.
OS Mus sp.
OS Chimeric.
XX
CC PN WO2019175125-A1.
XX
CC PD 19-SEP-2019.
XX
CC PF 12-MAR-2019; 2019WO-EP056067.
XX
PR 13-MAR-2018; 2018EP-00161340.
XX
CC PA (HOFF ) HOFFMANN LA ROCHE & CO AG F.
CC PA (HOFF ) HOFFMANN LA ROCHE INC.
XX
CC PI Claus C, Ferrara Koller C, Klein C, Sam J, Umana P;
XX
DR WPI; 2019-805897/76.
XX
CC PT 4-1BB (CD137) agonist is used for treating or delaying progression of
CC PT cancer, where 4-1BB agonist is used in combination with HER-2 targeting
CC PT agent and 4-1BB agonist, which is antigen binding molecule comprising one
CC PT antigen binding domain.
XX
CC PS Disclosure; SEQ ID NO 96; 142pp; English.
XX
CC The present invention relates to a novel 4-1BB (CD137) agonist e.g.,
CC antigen binding molecule useful for treating or delaying progression of
CC cancer. The antigen binding molecule comprises heavy chain and light
CC chain variable region CDRs corresponds to SEQ ID NO: 9-14 (see BGU00922-
CC BGU00927). The invention further relates to: (1) a pharmaceutical product
CC comprises first composition comprising as active ingredient a 4-1BB
CC (CD137) agonist and a pharmaceutically acceptable carrier and second
CC composition comprising as active ingredient a HER-2 targeting agent and a
CC pharmaceutically acceptable carrier; (2) a pharmaceutical composition
CC comprises a 4-1BB agonist and a HER-2 targeting agent; (3) a method for
CC using the 4-1BB agonist and HER-2 targeting agent for preparing a
CC medicament for treating or delaying progression of a proliferative
CC disease; and (4) a method for treating or delaying progression of cancer
CC in a subject. The agonist of the invention is also used for preventing
CC cancer is chosen from breast cancer, ovarian cancer, stomach cancer,
CC gastric cancer, oesophageal cancer, lung cancer, uterine cancer, salivary
CC duct carcinoma, bladder cancer, endometrial cancer, pancreatic cancer,
CC colon cancer, prostate cancer, and/or head and neck cancer.
XX
SQ Sequence 120 AA;
ALIGNMENT:
Query Match 100.0%; Score 645; Length 120;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
BHL24546
ID BHL24546 standard; protein; 120 AA.
XX
AC BHL24546;
XX
DT 30-APR-2020 (first entry)
XX
DE Anti-HER2 trastuzumab heavy chain variable region, SEQ ID 64.
XX
KW CD340; ERBB2; HER2; antibody therapy; c-neu protein; cancer;
KW cluster of differentiation 340; cytostatic;
KW epidermal growth factor receptor 2; heavy chain variable region;
KW immune stimulation; metastasis; monoclonal antibody; neu; p185 protein;
KW proto-oncogene Neu; receptor tyrosine-protein kinase erbB-2; solid tumor;
KW therapeutic; trastuzumab.
XX
OS Unidentified.
XX
CC PN WO2020043683-A1.
XX
CC PD 05-MAR-2020.
XX
CC PF 27-AUG-2019; 2019WO-EP072754.
XX
PR 27-AUG-2018; 2018EP-00191041.
XX
CC PA (PIER-) PIERIS PHARM GMBH.
XX
CC PI Bruns I, Matis L, Olwill S, Jaquin T;
XX
DR WPI; 2020-19381C/023.
XX
CC PT Treating cancer in human, by administering cluster of differentiation
CC PT 137/human epidermal growth factor receptor 2 bispecific agent comprising
CC PT complementarity determining regions and programmed cell death protein 1
CC PT axis inhibitor.
XX
CC PS Claim 1; SEQ ID NO 64; 78pp; English.
XX
CC The present invention relates to a novel method for treating cancer in
CC human. The method comprises administering CD137 (4-1 BB)/epidermal growth
CC factor receptor 2, (HER2, HER2/neu, receptor tyrosine-protein kinase erbB
CC -2, cluster of differentiation 340 (CD340), proto-oncogene Neu, ERBB2, c-
CC neu, or p185) bispecific agent comprising CDRs and programmed cell death
CC protein 1 (PD-1, cluster of differentiation 279 or CD279) axis inhibitor
CC e.g., antibody. The invention further relates to: (1) a combination
CC comprising an CD137/HER2 bispecific agent antibody; and (2) a kit of part
CC comprises a pharmaceutical composition comprising the CD137/HER2
CC bispecific agent antibody and the PD-1 axis inhibitor. The method and
CC composition of the invention is also used for enhancing immune response
CC in an individual having HER2-positive advanced or metastatic solid
CC tumors.
XX
SQ Sequence 120 AA;
ALIGNMENT:
Query Match 100.0%; Score 645; Length 120;
Best Local Similarity 100.0%;
Matches 120; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
Alignment of SEQ ID NO: 203 (anti-HER2 VL) with CLAUS’ SEQ ID NO: 97
Query Match 99.1%; Score 557; DB 1; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
Qy 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK 107
Alignment of SEQ ID NO: 203 (anti-HER2 VL) with BRUNS’ SEQ ID NO: 65
US-17-822-750A-203
Query Match 100.0%; Score 557; DB 1; Length 108;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
Qy 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIK 107
Alignment of SEQ ID NO: 205
US-17-822-737-188
Sequence 188, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 188
LENGTH: 726
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..726
QUALIFIERS: note = Anti-EGFR HC-anti-CD137 scFv-IgG1-LALA- Positive
Charge Linker(HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..726
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 90.6%; Score 3501; Length 726;
Best Local Similarity 91.5%;
Matches 665; Conservative 20; Mismatches 38; Indels 4; Gaps 2;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
|||||||||||||||||||||||||||:: : :|||||||||||||: |: : | | |
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFSLTNYGVHWVRQAPGKGLEWLGVIW-SGGNTDY 59
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
| ||||| | :||: |||||||||||||||||:| | ||||||:|||||
Db 60 ATEFTSRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARALDYYDYEFAYWGQGTMVTVSS 119
Qy 121 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||| |:||| |||||||||||||||||||||||||||||||||||||||
Db 120 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 179
Qy 181 GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESK---YGPPCPPCPAPEAAGG 237
||||||||||||||||||:|| |||:||||||||||||| | ||||||||||||
Db 180 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGG 239
Qy 238 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN 297
|||||||||||||||||||||||||||||| |||||:|||||||||||||||||||||:|
Db 240 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 299
Qy 298 STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE 357
||||||||||||||||||||||||||||| ||: |||||||||||||||||||||||:||
Db 300 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 359
Qy 358 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW 417
|||||||||||||||||||||||||||||||||||||||||||||||||||:||||||||
Db 360 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 419
Qy 418 QEGNVFSCSVMHEALHNHYTQKSLSLSLGKGRPGSGRPGSGRPGSGRPGSDIQMTQSPSS 477
|:||||||||||||||||||||||||| ||||||||||||||||||||||||||||||||
Db 420 QQGNVFSCSVMHEALHNHYTQKSLSLSPGKGRPGSGRPGSGRPGSGRPGSDIQMTQSPSS 479
Qy 478 VSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTD 537
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 480 VSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTD 539
Qy 538 FTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSGG 597
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 540 FTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSGG 599
Qy 598 GGSGGGGSQVQLVQSGAEVKKPGASVKASCKASGFNIQDTYIHWVRQAPGQGLEWMGRID 657
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 600 GGSGGGGSQVQLVQSGAEVKKPGASVKASCKASGFNIQDTYIHWVRQAPGQGLEWMGRID 659
Qy 658 PANGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTGNLHYALMDYWGQG 717
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 660 PANGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTGNLHYALMDYWGQG 719
Qy 718 TSVTVSS 724
|||||||
Db 720 TSVTVSS 726
RESULT 10
US-17-822-737-231
Sequence 231, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 231
LENGTH: 726
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..726
QUALIFIERS: note = Anti-EGFR HC-anti-CD137 scFv-IgG1-LALA- Positive
Charge Linker(HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..726
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 90.6%; Score 3499; Length 726;
Best Local Similarity 91.3%;
Matches 664; Conservative 21; Mismatches 38; Indels 4; Gaps 2;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
|||||||||||||||||||||||||||:: : :|||||||||||||: |: : | | |
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFSLTNYGVHWVRQAPGKGLEWLGVIW-SGGNTDY 59
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
: ||||| | :||: |||||||||||||||||:| | ||||||:|||||
Db 60 GNEFTSRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARALDYYDYEFAYWGQGTMVTVSS 119
Qy 121 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||| |:||| |||||||||||||||||||||||||||||||||||||||
Db 120 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 179
Qy 181 GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESK---YGPPCPPCPAPEAAGG 237
||||||||||||||||||:|| |||:||||||||||||| | ||||||||||||
Db 180 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGG 239
Qy 238 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN 297
|||||||||||||||||||||||||||||| |||||:|||||||||||||||||||||:|
Db 240 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 299
Qy 298 STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE 357
||||||||||||||||||||||||||||| ||: |||||||||||||||||||||||:||
Db 300 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 359
Qy 358 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW 417
|||||||||||||||||||||||||||||||||||||||||||||||||||:||||||||
Db 360 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 419
Qy 418 QEGNVFSCSVMHEALHNHYTQKSLSLSLGKGRPGSGRPGSGRPGSGRPGSDIQMTQSPSS 477
|:||||||||||||||||||||||||| ||||||||||||||||||||||||||||||||
Db 420 QQGNVFSCSVMHEALHNHYTQKSLSLSPGKGRPGSGRPGSGRPGSGRPGSDIQMTQSPSS 479
Qy 478 VSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTD 537
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 480 VSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTD 539
Qy 538 FTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSGG 597
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 540 FTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSGG 599
Qy 598 GGSGGGGSQVQLVQSGAEVKKPGASVKASCKASGFNIQDTYIHWVRQAPGQGLEWMGRID 657
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 600 GGSGGGGSQVQLVQSGAEVKKPGASVKASCKASGFNIQDTYIHWVRQAPGQGLEWMGRID 659
Qy 658 PANGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTGNLHYALMDYWGQG 717
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 660 PANGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTGNLHYALMDYWGQG 719
Qy 718 TSVTVSS 724
|||||||
Db 720 TSVTVSS 726
RESULT 11
US-17-822-737-260
Sequence 260, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 260
LENGTH: 726
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..726
QUALIFIERS: note = Anti-EGFR HC-anti-CD137-1 scFv-IgG1-LALA- Positive
Charge Linker(HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..726
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 90.4%; Score 3494; Length 726;
Best Local Similarity 91.2%;
Matches 663; Conservative 22; Mismatches 38; Indels 4; Gaps 2;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
|||||||||||||||||||||||||||:: : :|||||||||||||: |: : | | |
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFSLTNYGVHWVRQAPGKGLEWLGVIW-SGGNTDY 59
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
: ||||| | :||: |||||||||||||||||:| | ||||||:|||||
Db 60 GNEFTSRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARALDYYDYEFAYWGQGTMVTVSS 119
Qy 121 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||| |:||| |||||||||||||||||||||||||||||||||||||||
Db 120 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 179
Qy 181 GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESK---YGPPCPPCPAPEAAGG 237
||||||||||||||||||:|| |||:||||||||||||| | ||||||||||||
Db 180 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGG 239
Qy 238 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN 297
|||||||||||||||||||||||||||||| |||||:|||||||||||||||||||||:|
Db 240 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 299
Qy 298 STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE 357
||||||||||||||||||||||||||||| ||: |||||||||||||||||||||||:||
Db 300 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 359
Qy 358 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW 417
|||||||||||||||||||||||||||||||||||||||||||||||||||:||||||||
Db 360 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 419
Qy 418 QEGNVFSCSVMHEALHNHYTQKSLSLSLGKGRPGSGRPGSGRPGSGRPGSDIQMTQSPSS 477
|:||||||||||||||||||||||||| ||||||||||||||||||||||||||||||||
Db 420 QQGNVFSCSVMHEALHNHYTQKSLSLSPGKGRPGSGRPGSGRPGSGRPGSDIQMTQSPSS 479
Qy 478 VSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTD 537
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 480 VSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTD 539
Qy 538 FTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSGG 597
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 540 FTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSGG 599
Qy 598 GGSGGGGSQVQLVQSGAEVKKPGASVKASCKASGFNIQDTYIHWVRQAPGQGLEWMGRID 657
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 600 GGSGGGGSQVQLVQSGAEVKKPGASVKASCKASGFNIQDTYIHWVRQAPGQGLEWMGRID 659
Qy 658 PANGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTGNLHYALMDYWGQG 717
||:|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 660 PASGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTGNLHYALMDYWGQG 719
Qy 718 TSVTVSS 724
|||||||
Db 720 TSVTVSS 726
RESULT 12
US-17-822-737-282
Sequence 282, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 282
LENGTH: 726
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..726
QUALIFIERS: note = Anti-EGFR HC-anti-CD137-2 scFv-IgG1-LALA- Positive
Charge Linker (HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..726
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 90.3%; Score 3490; Length 726;
Best Local Similarity 91.1%;
Matches 662; Conservative 22; Mismatches 39; Indels 4; Gaps 2;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
|||||||||||||||||||||||||||:: : :|||||||||||||: |: : | | |
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFSLTNYGVHWVRQAPGKGLEWLGVIW-SGGNTDY 59
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
: ||||| | :||: |||||||||||||||||:| | ||||||:|||||
Db 60 GNEFTSRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARALDYYDYEFAYWGQGTMVTVSS 119
Qy 121 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||| |:||| |||||||||||||||||||||||||||||||||||||||
Db 120 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 179
Qy 181 GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESK---YGPPCPPCPAPEAAGG 237
||||||||||||||||||:|| |||:||||||||||||| | ||||||||||||
Db 180 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGG 239
Qy 238 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN 297
|||||||||||||||||||||||||||||| |||||:|||||||||||||||||||||:|
Db 240 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 299
Qy 298 STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE 357
||||||||||||||||||||||||||||| ||: |||||||||||||||||||||||:||
Db 300 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 359
Qy 358 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW 417
|||||||||||||||||||||||||||||||||||||||||||||||||||:||||||||
Db 360 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 419
Qy 418 QEGNVFSCSVMHEALHNHYTQKSLSLSLGKGRPGSGRPGSGRPGSGRPGSDIQMTQSPSS 477
|:||||||||||||||||||||||||| ||||||||||||||||||||||||||||||||
Db 420 QQGNVFSCSVMHEALHNHYTQKSLSLSPGKGRPGSGRPGSGRPGSGRPGSDIQMTQSPSS 479
Qy 478 VSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTD 537
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 480 VSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTD 539
Qy 538 FTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSGG 597
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 540 FTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSGG 599
Qy 598 GGSGGGGSQVQLVQSGAEVKKPGASVKASCKASGFNIQDTYIHWVRQAPGQGLEWMGRID 657
||||||||||||||||||||||||||| ||||||||||||||||||||||||||||||||
Db 600 GGSGGGGSQVQLVQSGAEVKKPGASVKVSCKASGFNIQDTYIHWVRQAPGQGLEWMGRID 659
Qy 658 PANGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTGNLHYALMDYWGQG 717
||:|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 660 PASGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTGNLHYALMDYWGQG 719
Qy 718 TSVTVSS 724
|||||||
Db 720 TSVTVSS 726
RESULT 13
US-17-822-737-189
Sequence 189, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 189
LENGTH: 726
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..726
QUALIFIERS: note = Anti-EGFR HC-anti-CD137 scFv-IgG1-LALA-Negative
Charge Linker(HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..726
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 90.0%; Score 3477; Length 726;
Best Local Similarity 90.8%;
Matches 660; Conservative 20; Mismatches 43; Indels 4; Gaps 2;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
|||||||||||||||||||||||||||:: :|||||||||||||: |: : | | |
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFSLTTYGVHWVRQAPGKGLEWLGVIW-SGGNTDY 59
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
: ||||| | :||: |||||||||||||||||:| | ||||||:|||||
Db 60 GNEFTSRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARALDYYDYEFAYWGQGTMVTVSS 119
Qy 121 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||| |:||| |||||||||||||||||||||||||||||||||||||||
Db 120 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 179
Qy 181 GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESK---YGPPCPPCPAPEAAGG 237
||||||||||||||||||:|| |||:||||||||||||| | ||||||||||||
Db 180 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGG 239
Qy 238 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN 297
|||||||||||||||||||||||||||||| |||||:|||||||||||||||||||||:|
Db 240 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 299
Qy 298 STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE 357
||||||||||||||||||||||||||||| ||: |||||||||||||||||||||||:||
Db 300 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 359
Qy 358 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW 417
|||||||||||||||||||||||||||||||||||||||||||||||||||:||||||||
Db 360 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 419
Qy 418 QEGNVFSCSVMHEALHNHYTQKSLSLSLGKGRPGSGRPGSGRPGSGRPGSDIQMTQSPSS 477
|:||||||||||||||||||||||||| ||| |||| |||| |||| |||||||||||||
Db 420 QQGNVFSCSVMHEALHNHYTQKSLSLSPGKGEPGSGEPGSGEPGSGEPGSDIQMTQSPSS 479
Qy 478 VSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTD 537
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 480 VSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTD 539
Qy 538 FTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSGG 597
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 540 FTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSGG 599
Qy 598 GGSGGGGSQVQLVQSGAEVKKPGASVKASCKASGFNIQDTYIHWVRQAPGQGLEWMGRID 657
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 600 GGSGGGGSQVQLVQSGAEVKKPGASVKASCKASGFNIQDTYIHWVRQAPGQGLEWMGRID 659
Qy 658 PANGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTGNLHYALMDYWGQG 717
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 660 PANGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTGNLHYALMDYWGQG 719
Qy 718 TSVTVSS 724
|||||||
Db 720 TSVTVSS 726
RESULT 14
US-17-822-737-259
Sequence 259, US/17822737
Publication No. US20230067770A1
GENERAL INFORMATION
APPLICANT: SHANGHAI HENLIUS BIOTECH, INC (en)
TITLE OF INVENTION: Anti-CD137 constructs, etc. (en)
FILE REFERENCE: FPCH22160242
CURRENT APPLICATION NUMBER: US/17/822,737
CURRENT FILING DATE: 2022-08-26
NUMBER OF SEQ ID NOS: 282
SEQ ID NO 259
LENGTH: 726
TYPE: PRT
FEATURE:
NAME/KEY: CHAIN
LOCATION: 1..726
QUALIFIERS: note = Anti-EGFR HC-anti-CD137 scFv-IgG1-LALA-Negative
Charge Linker(HCC)
FEATURE:
NAME/KEY: source
LOCATION: 1..726
QUALIFIERS: mol_type = protein
organism = synthetic construct
Query Match 89.9%; Score 3472; Length 726;
Best Local Similarity 90.6%;
Matches 659; Conservative 21; Mismatches 43; Indels 4; Gaps 2;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
|||||||||||||||||||||||||||:: :|||||||||||||: |: : | | |
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFSLTTYGVHWVRQAPGKGLEWLGVIW-SGGNTDY 59
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
: ||||| | :||: |||||||||||||||||:| | ||||||:|||||
Db 60 GNEFTSRFTISRDNAKNSLYLQMNSLRAEDTAVYYCARALDYYDYEFAYWGQGTMVTVSS 119
Qy 121 ASTKGPSVFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||| |:||| |||||||||||||||||||||||||||||||||||||||
Db 120 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 179
Qy 181 GLYSLSSVVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESK---YGPPCPPCPAPEAAGG 237
||||||||||||||||||:|| |||:||||||||||||| | ||||||||||||
Db 180 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPEAAGG 239
Qy 238 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFN 297
|||||||||||||||||||||||||||||| |||||:|||||||||||||||||||||:|
Db 240 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 299
Qy 298 STYRVVSVLTVLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEE 357
||||||||||||||||||||||||||||| ||: |||||||||||||||||||||||:||
Db 300 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 359
Qy 358 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRW 417
|||||||||||||||||||||||||||||||||||||||||||||||||||:||||||||
Db 360 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 419
Qy 418 QEGNVFSCSVMHEALHNHYTQKSLSLSLGKGRPGSGRPGSGRPGSGRPGSDIQMTQSPSS 477
|:||||||||||||||||||||||||| ||| |||| |||| |||| |||||||||||||
Db 420 QQGNVFSCSVMHEALHNHYTQKSLSLSPGKGEPGSGEPGSGEPGSGEPGSDIQMTQSPSS 479
Qy 478 VSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTD 537
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 480 VSASVGDRVTITCKASQPINTYLSWYQQKPGKAPKLLIYRVNRKVDGVPSRFSGSGSGTD 539
Qy 538 FTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSGG 597
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 540 FTLTISSLQPEDFATYYCLQYLDFPYTFGGGTKLEIKRGGGGSGGGGSGGGGSGGGGSGG 599
Qy 598 GGSGGGGSQVQLVQSGAEVKKPGASVKASCKASGFNIQDTYIHWVRQAPGQGLEWMGRID 657
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 600 GGSGGGGSQVQLVQSGAEVKKPGASVKASCKASGFNIQDTYIHWVRQAPGQGLEWMGRID 659
Qy 658 PANGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTGNLHYALMDYWGQG 717
||:|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 660 PASGNSEYAQKFQGRVTMTRDTSTSTVYMELSSLRSEDTAVYYCTTGNLHYALMDYWGQG 719
Qy 718 TSVTVSS 724
|||||||
Db 720 TSVTVSS 726
Alignment of SEQ ID NO: 185
BHL24562
ID BHL24562 standard; protein; 214 AA.
XX
AC BHL24562;
XX
DT 30-APR-2020 (first entry)
XX
DE Anti-HER2 trastuzumab light chain, SEQ ID 80.
XX
KW CD340; ERBB2; HER2; antibody therapy; c-neu protein; cancer;
KW cluster of differentiation 340; cytostatic;
KW epidermal growth factor receptor 2; immune stimulation; light chain;
KW metastasis; monoclonal antibody; neu; p185 protein; proto-oncogene Neu;
KW receptor tyrosine-protein kinase erbB-2; solid tumor; therapeutic;
KW trastuzumab.
XX
OS Unidentified.
XX
CC PN WO2020043683-A1.
XX
CC PD 05-MAR-2020.
XX
CC PF 27-AUG-2019; 2019WO-EP072754.
XX
PR 27-AUG-2018; 2018EP-00191041.
XX
CC PA (PIER-) PIERIS PHARM GMBH.
XX
CC PI Bruns I, Matis L, Olwill S, Jaquin T;
XX
DR WPI; 2020-19381C/023.
DR N-PSDB; BHL24590.
XX
CC PT Treating cancer in human, by administering cluster of differentiation
CC PT 137/human epidermal growth factor receptor 2 bispecific agent comprising
CC PT complementarity determining regions and programmed cell death protein 1
CC PT axis inhibitor.
XX
CC PS Claim 23; SEQ ID NO 80; 78pp; English.
XX
CC The present invention relates to a novel method for treating cancer in
CC human. The method comprises administering CD137 (4-1 BB)/epidermal growth
CC factor receptor 2, (HER2, HER2/neu, receptor tyrosine-protein kinase erbB
CC -2, cluster of differentiation 340 (CD340), proto-oncogene Neu, ERBB2, c-
CC neu, or p185) bispecific agent comprising CDRs and programmed cell death
CC protein 1 (PD-1, cluster of differentiation 279 or CD279) axis inhibitor
CC e.g., antibody. The invention further relates to: (1) a combination
CC comprising an CD137/HER2 bispecific agent antibody; and (2) a kit of part
CC comprises a pharmaceutical composition comprising the CD137/HER2
CC bispecific agent antibody and the PD-1 axis inhibitor. The method and
CC composition of the invention is also used for enhancing immune response
CC in an individual having HER2-positive advanced or metastatic solid
CC tumors.
XX
SQ Sequence 214 AA;
ID BHL95015 standard; protein;
ALIGNMENT:
Query Match 100.0%; Score 1110; Length 214;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
Qy 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPP 120
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
Prosecution Insights