NON-BLOCKING HUMAN CCR8 BINDERS

Notice of Pre-AIA or AIA Status The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA . DETAILED ACTION RESPONSE TO AMENDMENT Status of Application/Amendments/claims 2. Applicant’s amendment filed July 08, 2026 is acknowledged. Claims 1-3, 5 and 11 are canceled. Claims 4,7,13-14 and 16 are amended. Claims 17-18 are newly added. Claims 4, 6-10,12-16 and new claims 17-18 are pending in this application and under examination in this office action. 3. Applicant’s arguments filed on July 08, 2026 have been fully considered but they are not deemed to be persuasive for the reasons set forth below. Claim Rejections/Objections Withdrawn 4. The objection to claims 1-2 and 13-14 is withdrawn in response to Applicant’s amendment to the claims and cancelation of claims 1-2. The rejection of claims 2 and 13-16 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in response to Applicant’s amendment to the claims and cancelation of claim 2. The rejection of claims 1-2, 4-6, 9-10 and 12 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in response to Applicant’s amendment to the claims and cancelation of claims 1-2 and 5. Claim Rejections/Objections Maintained In view of the amendment filed on July 08, 2026, the following rejections are maintained. Claim Rejections - 35 USC § 112 5. The following is a quotation of the first paragraph of 35 U.S.C. 112(a): (a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention. The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112: The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention. Claims 13-16 and 18 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention. The rejection is maintained for the reasons of record and the reasons set forth below. Claims 13-15 as amended encompass treating a genus of tumor including all forms of cancers by the claimed single domain antibody (ScAb) moiety binding to hCCR8 of claim 4. Claim 16 as amended encompasses a genus of a human CCR8 (hCCR8) binder, wherein the binder is a single domain antibody (ScAb) comprising CDRs1-3, wherein the CDRs1-3 are selected from the respective CDR1s, CDR2s and CDR3s comprised in SEQ ID NOs: 8, 9 or 10, and wherein all of the CDRs1-3 are defined by the Kabat, Chothia, AHo or IMGT information system. Claim 18 as amended encompasses a genus of ScAb moiety of claim 4 binding to aa 2-19 of hCCR8. Briefly, Applicant has not disclosed sufficient species for using the claimed hCCR8 ScAb of claim 4 for treating the claimed genus of tumor including all forms of cancers and cancers recited in claim 14. Based on Applicant’s own admission, VHH-69 (SEQ ID NO:10) binding hCCR8 without blocking hCCR8 (Examples 15-23) or a mouse VHH (VHH-06) binding to mouse CCR8 (mCCR8) without blocking mCCR8 does not have ADCC toxicity and cannot block mCCR8 Treg cells to reduce a tumor size (see Examples 8-10). Based on Applicant’s own admission, only fusion proteins comprising VHH-69 fused to a human IgG1-Fc: VHH-Fc-218 (SEQ ID NO:27), VHH-Fc-219 (SEQ ID NO:21), VHH-Fc-220 (SEQ ID NO:22), VHH-Fc-262 (SEQ ID NO:29) and VHH-Fc-264 (SEQ ID NO:26) possess ADCC toxicity in HEK293 cells expressing hCCR8 (See Examples 20 and 23 and figures 9-16): VHH-Fc-218 (SEQ ID NO:27): VHH-69(SEQ ID NO:10)-a human IgG short hinge and IgG Fc domain (SEQ ID NO:30)); VHH-Fc-219 (SEQ ID NO:21): VHH-69(SEQ ID NO:10)-(GS)10 linker(SEQ ID NO:20)2-a human IgG short hinge and IgG1 Fc domain (SEQ ID NO:30); VHH-Fc-220 (SEQ ID NO:22): VHH-69 (SEQ ID NO:10)-GS(20) linker (SEQ ID NO:20)4-a human IgG short hinge and IgG1 Fc domain (SEQ ID NO:30); VHH-Fc-262 (SEQ ID NO:29): VHH-124-an IgG1 short hinge domain and IgG1 Fc domain (SEQ ID NO:30); VHH-Fc-264 (SEQ ID NO:26): VHH-124-(GS)20(SEQ ID NO:24)-an IgG1 short hinge domain and IgG1 Fc domain (SEQ ID NO:30). Thus, Applicant is not in possession of using the claimed genus of ScAb moiety binding to hCCR8 recited claim 4 without an IgG1 Fc domain for inducing cytotoxicity including for inducing ADCC, CDC, ADCP, activating T-cells or cytotoxic payload for treating all forms of tumor or cancer. Applicant also has not disclosed sufficient species for the broad genus of hCCR8 ScAb comprising CDR1-3 selected from the respective CDR1s, CDR2s and CDR3s comprised in SEQ ID NOs: 8, 9 or 10 as defined by the Kabat, Chothia, AHo or IMGT information system recited in claim 16. The specification only describes the following VHH and VHH-Fc fusion proteins that bind to hCCR8 and non-blocking hCCR8 and their activities (see Examples 14-23 and figures 9-16): Name SEQ ID NO: Fragments Non-blocking ADCC VHH-69 10 VHH-69 + - VHH-123 8 VHH-69(E1D,N55S,D65G) + - VHH-124 9 VHH-69(E1D,N55K,D65G) + - VHH-Fc-218 27 VHH-69-hIgG1-Fc + + VHH-Fc-219 21 VHH-69-(GS)10-hIgG1-Fc + + VHH-Fc-220 22 VHH-69-(GS)20-hIgG1-Fc + + VHH-Fc-262 29 VHH124-hIgG1-Fc + + VHH-Fc-264 26 VHH214-(GS)20-hIgG1-Fc + + Based on para. [0090]-[0100] of the specification (based on the published Applciation), the claimed hCCR8 ScAb recited in instant claim 16 also encompasses humanized hCCR8 ScAb. It is known that the humanized ScAb relies specific CDRs1-3 defined by the specific number system in order to generate effective ScAb capable of binding to hCCR8. The specification fails to teach whether all of ScAb including humanized ScAb comprising CDR1-3 selected from the respective CDR1s, CDR2s and CDR3s comprised in SEQ ID NOs: 8, 9 or 10 as defined by the Kabat, Chothia, AHo or IMGT information system recited in claim 16 are capable of binding to hCCR8. The specification fails to provide sufficient information or evidence to demonstrate that Applicant is not in possession of other structurally and functionally undefined ScAb including humanized ScAb comprising CDRs1-3 comprised in SEQ ID NOs: 8, 9 or 10 as defined by the Kabat, Chothia, AHo or IMGT information system recited in claim 16 that are capable of binding hCCR8. The specification in Example 15 only discloses VHH-69 binding to “SEQ ID NO:32, delta 18-3xHA” (see p. 55 and Example 15). Taken together, the specification provides no well-established structural and functional relationship or correlation between the claimed hCCR8 ScAb recited in claim 4 and VHH-Fc-218, VHH-Fc-219, VHH-Fc-220, VHH-Fc-262 and VHH-Fc-264 shown in Examples 20 and 23 and figures 9-16 of the specification in reducing a tumor size or inducing ADCC toxicity for treating all forms of tumors and cancers. The specification also provides no well-established structural and functional relationship or correlation between the claimed genus of hCCR8 ScAb including humanized hCCR8 ScAb recited in claim 16 and VHH-69 or VHH-Fc-218, VHH-Fc-219, VHH-Fc-220, VHH-Fc-262 and VHH-Fc-264 shown in Examples of the specification. Since there is no structural and functional relationship or correlation between the claimed hCCR8 ScAb recited in claim4 and VHH-Fc-218, VHH-Fc-219, VHH-Fc-220, VHH-Fc-262 and VHH-Fc-264 shown in Examples 20 and 23 and figures 9-16 of the specification in reducing a tumor size or inducing ADCC toxicity for treating all forms of tumors and cancers, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention. Since there is no well-established structural and functional relationship or correlation between the claimed ScAb including humanized ScAb comprising CDRs1-3 comprised in SEQ ID NOs: 8, 9 or 10 as defined by the Kabat, Chothia, AHo or IMGT information system recited in claim 16 and VHH-Fc-218, VHH-Fc-219, VHH-Fc-220, VHH-Fc-262 and VHH-Fc-264 in binding hCCR8, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of using the genus of hCCR8 ScAb of claim 4 for treating a genus of tumor or cancer or and VHH-Fc-218, VHH-Fc-219, VHH-Fc-220, VHH-Fc-262 and VHH-Fc-264 or the claimed ScAb including humanized ScAb comprising CDRs1-3 comprised in SEQ ID NOs: 8, 9 or 10 as defined by the Kabat, Chothia, AHo or IMGT information system recited in claim 16. Response to Arguments On p. 8-9 of the response, Applicant argues that the rejection has been overcome in view of amendment to claim 4. Applicant's arguments have been fully considered but they are not found persuasive. Contrary to Applicant's arguments, the examiner asserts that based on MPEP §2163, MPEP §§2163.01-2163.03, the specification fails to provide sufficient description or information or evidence to demonstrate that Applicant is in possession of using the claimed hCCR8 ScAb of claim 4 for treating all forms of tumors and cancers or the claimed genus of ScAb including humanized ScAb comprising CDRs1-3 comprised in SEQ ID NOs: 8, 9 or 10 as defined by the Kabat, Chothia, AHo or IMGT information system recited in claim 16 or the claimed CCR8 ScAb of claim 4 binding to aa 2-19 of hCCR8 because: i. There is no well-established structural and functional relationship or correlation between the claimed hCCR8 ScAb of claim 4 and VHH-Fc-218 (SEQ ID NO:27), VHH-Fc-219 (SEQ ID NO:21), VHH-Fc-220 (SEQ ID NO:22), VHH-Fc-262 (SEQ ID NO:29) and VHH-Fc-264 (SEQ ID NO:26) in reducing a tumor size shown in Examples 8-10 or in inducing ADCC toxicity in HEK293 cells expressing hCCR8 shown in Examples 20 and 23 and figures 9-16): Based on Applicant’s own admission, VHH-69 (SEQ ID NO:10) binding hCCR8 without blocking hCCR8 (Examples 15-23) or a mouse VHH (VHH-06) binding to mouse CCR8 (mCCR8) without blocking mCCR8 does not have ADCC toxicity and cannot block mCCR8 Treg cells to reduce a tumor size (see Examples 8-10). Based on Applicant’s own admission, only fusion proteins comprising VHH-69 fused to a human IgG1-Fc: VHH-Fc-218 (SEQ ID NO:27), VHH-Fc-219 (SEQ ID NO:21), VHH-Fc-220 (SEQ ID NO:22), VHH-Fc-262 (SEQ ID NO:29) and VHH-Fc-264 (SEQ ID NO:26) possess ADCC toxicity in HEK293 cells expressing hCCR8 (See Examples 20 and 23 and figures 9-16): The specification fails to provide sufficient evidence to demonstrate that Applicant is in possession of using the claimed genus of ScAb moiety binding to hCCR8 recited claim 4 without an IgG1 Fc domain for inducing cytotoxicity including for inducing ADCC, CDC, ADCP, activating T-cells or cytotoxic payload for treating all forms of tumor or cancer. ii. The specification provides no well-established structural and functional relationship or correlation between ScAb including humanized ScAb comprising CDR1-3 selected from the respective CDR1s, CDR2s and CDR3s comprised in SEQ ID NOs: 8, 9 or 10 as defined by the Kabat, Chothia, AHo or IMGT information system recited in claim 16 and VHH-69 (SEQ ID NO:10), VHH-Fc-218 (SEQ ID NO:27), VHH-Fc-219 (SEQ ID NO:21), VHH-Fc-220 (SEQ ID NO:22), VHH-Fc-262 (SEQ ID NO:29) and VHH-Fc-264 (SEQ ID NO:26) binding to hCCR8. Based on para. [0090]-[0100] of the specification (based on the published Applciation), the claimed hCCR8 ScAb recited in instant claim 16 also encompasses humanized hCCR8 ScAb. It is known that the humanized ScAb relies specific CDRs1-3 defined by the specific number system in order to generate effective ScAb capable of binding to hCCR8. However, the specification fails to teach whether all of ScAb including humanized ScAb comprising CDR1-3 selected from the respective CDR1s, CDR2s and CDR3s comprised in SEQ ID NOs: 8, 9 or 10 as defined by the Kabat, Chothia, AHo or IMGT information system recited in claim 16 are capable of binding to hCCR8. The specification fails to provide sufficient information or evidence to demonstrate that Applicant is not in possession of other structurally and functionally undefined ScAb including humanized ScAb comprising CDRs1-3 comprised in SEQ ID NOs: 8, 9 or 10 as defined by the Kabat, Chothia, AHo or IMGT information system recited in claim 16 that are capable of binding hCCR8. iii. The specification fails to teach that the claimed hCCR8 ScAb of claim 4 can bind to aa 2-19 of hCCR8. Example 15 of the specification only discloses that VHH-69 binds to “SEQ ID NO:32, delta 18-3xHA” (see p. 55 and Example 15). Since the structural and functional relationship or correlation between the claimed hCCR8 ScAb recited in claim 4 and VHH-Fc-218, VHH-Fc-219, VHH-Fc-220, VHH-Fc-262 and VHH-Fc-264 shown in Examples 20 and 23 and figures 9-16 of the specification in reducing a tumor size or inducing ADCC toxicity for treating all forms of tumors and cancers is unknown, a skilled artisan cannot contemplate the functional correlations of the genus with the claimed invention. Since the common characteristics/features of other ScAb including humanized ScAb comprising CDR1-3 selected from the respective CDR1s, CDR2s and CDR3s comprised in SEQ ID NOs: 8, 9 or 10 as defined by the Kabat, Chothia, AHo or IMGT information system recited in claim 16 are unknown, a skilled artisan cannot envision the functional correlations of the genus with the claimed invention in view of MacCallum et al. (see p. 73, J. Mol. Biol.,1996; 262: 732-745, cited previously), Pascalis et al. (see p. 3079-3080 ; The Journal of Immunology, 2002; 169: 3076-3084, cited previously), Casset et al. (page 202, left col.; BBRC, 2003; 307: 198-205, cited previously), Vajdos et al. (see p. 416, left col ; J. Mol. Biol. 2002; 320: 415-428), Holm et al.(Mol. Immunol., 2007; 44: 1075-1084, cited previously) , Chen et al. (see p. 866 ; J. Mol. Bio., 1999; 293: 865-881, cited previously), Wu et al. (see p. 152, left col. ; J. Mol. Biol., 1999; 294:151-162, cited previously), Burgess et al. (J of Cell Bio. 1990, 111:2129-2138, cited previously), Bowie et al. (see col 2, p. 1306, Bowie et al. Science, 1990, 247:1306-1310, cited previously), Pawson et al. (see p. 445 the second column, first paragraph, Pawson et al. 2003, Science 300:445-452, cited previously), Alaoui-lsmaili et al. (see p. 502, right col., 2th paragraph; Alaoui-lsmaili et al., Cytokine Growth Factor Rev. 2009; 20:501-507, cited previously), Guo et al. (see p. 9207, left col., 2th paragraph, Guo et al., PNAS 2004; 101:9205-9210, cited previously) and Rudikoff et al. (see p. 1979; Proc. Natl. Acad. Sci. USA 1982 Vol. 79: page 1979, cited previously). Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of using the claimed hCCR8 ScAb of claim 4 for treating a genus of tumor or cancer or the claimed hCCR8 ScAb of claim 4 binding to aa 2-19 of hCCR8 or the claimed genus of ScAb including humanized ScAb comprising CDR1-3 selected from the respective CDR1s, CDR2s and CDR3s comprised in SEQ ID NOs: 8, 9 or 10 as defined by the Kabat, Chothia, AHo or IMGT information system recited in claim 16 binding to hCCR8. Based on MPEP § 2161.01 and §2163, “to satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116”. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description' inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus of using the claimed hCCR8 ScAb of claim 4 for treating the genus of tumor or cancer or the claimed hCCR8 ScAb of claim 4 for binding to aa 2-19 of hCCR8 or the genus of ScAb including humanized ScAb comprising CDR1-3 selected from the respective CDR1s, CDR2s and CDR3s comprised in SEQ ID NOs: 8, 9 or 10 as defined by the Kabat, Chothia, AHo or IMGT information system recited in claim 16 binding to hCCR8, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolating it. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483 and Centocor v. Abbott, 636 F.3d1341 (Fed. Cir. 2011) and AbbVie v. Janssen, 759 F.3d 1285 (Fed. Cir.2014). One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. Therefore, the claimed method of treating a tumor using the claimed hCCR8 ScAb of claim 4, the claimed hCCR8 ScAb of claim 4 binding to aa 2-19 of hCCR8, or the claimed ScAb including humanized ScAb comprising CDR1-3 selected from the respective CDR1s, CDR2s and CDR3s comprised in SEQ ID NOs: 8, 9 or 10 as defined by the Kabat, Chothia, AHo or IMGT information system recited in claim 16 binding to hCCR8 have not met the written description provision of 35 U.S.C. §112, first paragraph. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115). Applicant is directed to the Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, ¶ 1 "Written Description" Requirement. See MPEP § 2161.01 and 2163. Accordingly, the rejection of claims 13-16 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is maintained. New Grounds of Rejection Necessitated by the Amendment The following rejections are new grounds of rejections necessitated by the amendment filed on July 08, 2026. Claim Rejections - 35 USC § 112 6. The following is a quotation of 35 U.S.C. 112(b): (b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention. The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph: The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention. Claims 8 and 17-18 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, or for pre-AIA the applicant regards as the invention. Claims 8 and 17-18 are indefinite because: i. The term “less than 50%” in claim 8 is a relative term which renders the claim indefinite. The term “less than 50%” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Applicant fails to set forth the metes and bounds of what is encompassed within the definition of “less than 50%”. It is unclear what “less than 50%” is relative to. Since the metes and bounds are unknown, a skilled artisan cannot envision what would be considered as “inhibits signaling of human CCR8 by less than 50%” recited in the claim. Thus, the claim is indefinite. ii. The term “non-blocking hCCR8 binder” in claim 17 is a relative term which renders the claim indefinite. The term “non-blocking hCCR8 binder” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Applicant fails to set forth the metes and bounds of what is encompassed within the definition of “non-blocking hCCR8 binder”. It is unclear what “non-blocking hCCR8 binder” is relative to. Since the metes and bounds are unknown, a skilled artisan cannot envision what would be considered as “non-blocking hCCR8 binder” recited in the claim. Thus, the claim is indefinite. iii. The limitation “amino acids 2 to 19 of hCCR8” recited in claim 18 is unclear because based on the NCBI website, there are multiple hCCR8 sequences with different lengths. It is not known whether amino acids 2-19 in different hCCR8 amino acid sequences are identical and refer to the same epitope within hCCR8, which renders the claim indefinite. Claim Rejections - 35 USC § 112 (a) 7. Claim 18 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection. Claim 18 is directed to a hCCR8 ScAb binding to aa 2-19 of hCCR8 and wherein the hCCR8 comprising CDRs 1-3 recited in claim 4. The instant claim now recites a new limitation “binding to aa 2-19 of hCCR8”, which was not clearly disclosed in the specification and claims as filed, and now changes the scope of the instant disclosure as filed. Such new limitation recited in the present claim, which did not appear in the specification or original claims, as filed, introduces new concepts and violate the description requirement of the first paragraph of 35 U.S.C. 112. The specification fails to disclose the new limitation “binding to aa 2-19 of hCCR8”. The specification in Example 15 only discloses VHH-69 binding to “SEQ ID NO:32, delta 18-3xHA” (see p. 55 and Example 15). Applicant provides no guidance as to what is encompassed in the new limitation “binding to aa 2-19 of hCCR8”. Accordingly, in the absence of sufficient recitation for the new limitation “binding to aa 2-19 of hCCR8”, the specification does not provide adequate written description to support the new limitation “binding to aa 2-19 of hCCR8” recited in claim 18. Support is not found for the new limitation as disclosed in the original specification and thus the recitation constitutes new matter absent evidence for their support. Applicant is required to cancel the new matter in the reply to this office action. Alternatively, Applicant is invited to clearly point out the written support for the instant limitations. Conclusion Allowable Subject Matter 8. Claims 4, 6-7, 9-10 and 12 are allowed. 9. Claims 8 and 13-18 are rejected. Sequence alignment SEQ ID NO:26(VHH-264) 1 DVQLVESGGGLVQPGGSLRLSCTASGRTFTNYKSNYKMAWFRQAPGKARAFVGRTDWTGK 60 SEQ ID NO:29(VHH-262) 1 DVQLVESGGGLVQPGGSLRLSCTASGRTFTNYKSNYKMAWFRQAPGKARAFVGRTDWTGK 60 SEQ ID NO:22(VHH-Fc-220) 1 EVQLVESGGGLVQPGGSLRLSCTASGRTFTNYKSNYKMAWFRQAPGKARAFVGRTDWTGN 60 SEQ ID NO:8(VHH-123) 1 DVQLVESGGGLVQPGGSLRLSCTASGRTFTNYKSNYKMAWFRQAPGKARAFVGRTDWTGS 60 SEQ ID NO:9(VHH-124) 1 DVQLVESGGGLVQPGGSLRLSCTASGRTFTNYKSNYKMAWFRQAPGKARAFVGRTDWTGK 60 SEQ ID NO:10(VHH-69) 1 EVQLVESGGGLVQPGGSLRLSCTASGRTFTNYKSNYKMAWFRQAPGKARAFVGRTDWTGN 60 SEQ ID NO:1(CDR1) 1 -------------------------GRTFTNYKSNYK----------------------- 12 SEQ ID NO:2(CDR2) 1 ------------------------------------------------------TDWTGX 6 SEQ ID NO:3(CDR3) ------------------------------------------------------------ SEQ ID NO:4(FR1-25aa) 1 XVQLVESGGGLVQPGGSLRLSCTAS----------------------------------- 25 SEQ ID NO:5(FR2-17aa) 1--------------------------------------MAWFRQAPGKARAFVGR------ 17 SEQ ID NO:6(FR3-36aa) ------------------------------------------------------------- SEQ ID NO:7(FR4-11aa) ------------------------------------------------------------- SEQ ID NO:26(VHH-264) 61 SAIIANSVKGRFTISRDNAKNTVYLQMNSLRPEDTAVYYCAAGTTIGQYTYWGQGTLVTV 120 SEQ ID NO:29(VHH-262) 61 SAIIANSVKGRFTISRDNAKNTVYLQMNSLRPEDTAVYYCAAGTTIGQYTYWGQGTLVTV 120 SEQ ID NO:22(VHH-Fc-220) 61 SAIIANSVKDRFTISRDNAKNTVYLQMNSLRPEDTAVYYCAAGTTIGQYTYWGQGTLVTV 120 SEQ ID NO:8(VHH-123) 61 SAIIANSVKGRFTISRDNAKNTVYLQMNSLRPEDTAVYYCAAGTTIGQYTYWGQGTLVTV 120 SEQ ID NO:9(VHH-124) 61 SAIIANSVKGRFTISRDNAKNTVYLQMNSLRPEDTAVYYCAAGTTIGQYTYWGQGTLVTV 120 SEQ ID NO:10(VHH-69) 61 SAIIANSVKDRFTISRDNAKNTVYLQMNSLRPEDTAVYYCAAGTTIGQYTYWGQGTLVTV 120 SEQ ID NO:1(CDR1) ------------------------------------------------------------ SEQ ID NO:2(CDR2) 7 SA---------------------------------------------------------- 8 SEQ ID NO:3(CDR3) 1 ----------------------------------------AAGTTIGQYTY--------- 11 SEQ ID NO:34(CDR3) 1 ------------------------------------------GTTIGQYTY--------- 9 SEQ ID NO:4(FR1-25aa) ------------------------------------------------------------ SEQ ID NO:5(FR2-17aa) ------------------------------------------------------------ SEQ ID NO:6(FR3-36aa) 1 --IIANSVKXRFTISRDNAKNTVYLQMNSLRPEDTAVYYC-------------------- 36 SEQ UID NO:7(FR4-11aa) 1 ---------------------------------------------------WGQGTLVTV 9 SEQ ID NO:26(VHH-264) 121 SSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 180 SEQ ID NO:29(VHH-262) 121 SS--------------------DKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 160 SEQ ID NO:22(VHH-Fc-220) 121 SSGGGGSGGGGSGGGGSGGGGSDKTHTCPPCPAPELLGGPSVFLFPPKPKDTLMISRTPE 180 SEQ ID NO:8(VHH-123) 121 SS---------------------------------------------------------- 122 SEQ ID NO:9(VHH-124) 121 SS---------------------------------------------------------- 122 SEQ ID NO:10(VHH-69) 121 SS---------------------------------------------------------- 122 SEQ ID NO:4(FR1-25aa) ------------------------------------------------------------ SEQ ID NO:5(FR2-17aa) ------------------------------------------------------------ SEQ ID NO:6(FR3-36aa) ------------------------------------------------------------ SEQ ID NO:7(FR4-11aa) 10 SS---------------------------------------------------------- 11 SEQ ID NO:26(VHH-264) 181 VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE 240 SEQ ID NO:29(VHH-262) 161 VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE 220 SEQ ID NO:22(VHH-Fc-220) 181 VTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYNSTYRVVSVLTVLHQDWLNGKE 240 SEQ ID NO:26(VHH-264) 241 YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIA 300 SEQ ID NO:29(VHH-262) 221 YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIA 280 SEQ ID NO:22(VHH-Fc-220) 241 YKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSRDELTKNQVSLTCLVKGFYPSDIA 300 SEQ ID NO:26(VHH-264) 301 VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ 360 SEQ ID NO:29(VHH-262) 281 VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ 340 SEQ ID NO:22(VHH-Fc-220) 301 VEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQ 360 SEQ ID NO:26(VHH-264) 361 KSLSLSPG 368 SEQ ID NO:29(VHH-262) 341 KSLSLSPG 348 SEQ ID NO:22(VHH-Fc-220) 361 KSLSLSPG 368 10. The prior art made of record and not relied upon is considered pertinent to applicant's disclosure. WO2018220235 teaches an anti-MMP13 VHH comprising SEQ ID NO:10, which is 74.3% identical to instant SEQ ID NO:8, 73.9% identical to instant SEQ ID NO:9 or an anti-MMP13 construct (40E09-517A01 clone 71) comprising SEQ ID 163, which is 73.0% identical to instant SEQ ID NO:10 (see the sequence alignment below). SEQ ID NO:8 WO2018220235 BFW74884 ID BFW74884 standard; protein; 129 AA. XX AC BFW74884; XX DT 24-JAN-2019 (first entry) XX DE Anti-MMP13 immunoglobulin single variable domain VHH region, SEQ 10. XX KW MMP13; Metalloprotease-13; achondroplasia; antiarthritic; KW antibody production; antibody therapy; antiinflammatory; arthritis; KW chondrodystrophy; collagenase; cytostatic; degeneration; diagnostic test; KW dysplasia; gout; growth-disorder-gen.; heavy chain variable region; KW hernia; immuno-diagnosis; joint disease; matrix metalloproteinase 13; KW musculoskeletal-gen.; nanobody; osteoarthritis; osteochondritis; KW osteopathic; polychondritis; prophylactic to disease; KW psoriatic arthritis; rheumatoid arthritis; single domain antibody; KW therapeutic; vulnerary. XX OS Camelidae. XX CC PN WO2018220235-A1. XX CC PD 06-DEC-2018. XX CC PF 04-JUN-2018; 2018WO-EP064667. XX PR 02-JUN-2017; 2017EP-00174402. XX CC PA (MERE ) MERCK PATENT GMBH. CC PA (ABLY ) ABLYNX NV. XX CC PI Descamps F, Beste G, Hermans G, Guehring H, Toleikis L, Ladel C; XX DR WPI; 2018-96946V/01. XX CC PT Polypeptide comprises one immunoglobulin single variable domain binding CC PT matrix metalloproteinase, where matrix metalloproteinase is chosen from CC PT the group consisting of collagenase, matrix metalloproteinase-8, matrix CC PT metalloproteinase-l. XX CC PS Claim 43; SEQ ID NO 10; 122pp; English. XX CC The present invention relates to a novel polypeptide useful for treating CC or preventing matrix metalloproteinase (MMP) 13 associated diseases or CC disorders. The polypeptide comprises one immunoglobulin single variable CC domain (ISVD) binding to matrix metalloproteinase, where matrix CC metalloproteinase is selected from MMP13 (collagenase), MMP8 CC (collagenase), MMP1 (collagenase), MMP19 and MMP20 (enamelysin). The CC invention further provides: a method for treating, preventing or CC diagnosing diseases or disorders and its symptoms such as arthropathies CC and chondrodystrophies, arthritic diseases includes osteoarthritis, CC rheumatoid arthritis, gouty arthritis, psoriatic arthritis, traumatic CC rupture or detachment, achondroplasia, costochondritis, CC Spondyloepimetaphyseal dysplasia, spinal disc herniation, lumbar disk CC degeneration disease, degenerative joint disease, and relapsing CC polychondritis, osteochondritis dissecans and aggrecanopathies by CC administering the novel polypeptide; and a method for preparing the novel CC polypeptide. The present sequence represents an anti-MMP13 ISVD heavy CC chain variable region (VHH), which is used in the invention for treating CC or preventing diseases or disorders associated with MMP13. Note: SEQ ID CC 125 is mentioned in claim 40 but no corresponding sequence is provided in CC the patent. XX SQ Sequence 129 AA; Query Match 74.3%; Score 476.5; Length 129; Best Local Similarity 70.7%; Matches 94; Conservative 6; Mismatches 18; Indels 15; Gaps 2; Qy 1 DVQLVESGGGLVQPGGSLRLSCTASGRTFTNYKSNYKMAWFRQAPGKARAFVGRTDWTGS 60 |||||||||||||||||||||| |||||| |:| | |||||||| | || |:| Db 1 DVQLVESGGGLVQPGGSLRLSCAASGRTF----SSYAMGWFRQAPGKEREFVAAISWSGG 56 Qy 61 SAIIANSVKGRFTISRDNAKNTVYLQMNSLRPEDTAVYYCAAGTT-----------IGQY 109 | |:||||||||||||:||||||||||||||||||||| | :|:| Db 57 STYYADSVKGRFTISRDNSKNTVYLQMNSLRPEDTAVYYCTAALAVYGPNRYRYGPVGEY 116 Qy 110 TYWGQGTLVTVSS 122 |||||||||||| Db 117 NYWGQGTLVTVSS 129 SEQ ID NO:9 BFW74884 ID BFW74884 standard; protein; 129 AA. XX AC BFW74884; XX DT 24-JAN-2019 (first entry) XX DE Anti-MMP13 immunoglobulin single variable domain VHH region, SEQ 10. XX KW MMP13; Metalloprotease-13; achondroplasia; antiarthritic; KW antibody production; antibody therapy; antiinflammatory; arthritis; KW chondrodystrophy; collagenase; cytostatic; degeneration; diagnostic test; KW dysplasia; gout; growth-disorder-gen.; heavy chain variable region; KW hernia; immuno-diagnosis; joint disease; matrix metalloproteinase 13; KW musculoskeletal-gen.; nanobody; osteoarthritis; osteochondritis; KW osteopathic; polychondritis; prophylactic to disease; KW psoriatic arthritis; rheumatoid arthritis; single domain antibody; KW therapeutic; vulnerary. XX OS Camelidae. XX CC PN WO2018220235-A1. XX CC PD 06-DEC-2018. XX CC PF 04-JUN-2018; 2018WO-EP064667. XX PR 02-JUN-2017; 2017EP-00174402. XX CC PA (MERE ) MERCK PATENT GMBH. CC PA (ABLY ) ABLYNX NV. XX CC PI Descamps F, Beste G, Hermans G, Guehring H, Toleikis L, Ladel C; XX DR WPI; 2018-96946V/01. XX CC PT Polypeptide comprises one immunoglobulin single variable domain binding CC PT matrix metalloproteinase, where matrix metalloproteinase is chosen from CC PT the group consisting of collagenase, matrix metalloproteinase-8, matrix CC PT metalloproteinase-l. XX CC PS Claim 43; SEQ ID NO 10; 122pp; English. XX CC The present invention relates to a novel polypeptide useful for treating CC or preventing matrix metalloproteinase (MMP) 13 associated diseases or CC disorders. The polypeptide comprises one immunoglobulin single variable CC domain (ISVD) binding to matrix metalloproteinase, where matrix CC metalloproteinase is selected from MMP13 (collagenase), MMP8 CC (collagenase), MMP1 (collagenase), MMP19 and MMP20 (enamelysin). The CC invention further provides: a method for treating, preventing or CC diagnosing diseases or disorders and its symptoms such as arthropathies CC and chondrodystrophies, arthritic diseases includes osteoarthritis, CC rheumatoid arthritis, gouty arthritis, psoriatic arthritis, traumatic CC rupture or detachment, achondroplasia, costochondritis, CC Spondyloepimetaphyseal dysplasia, spinal disc herniation, lumbar disk CC degeneration disease, degenerative joint disease, and relapsing CC polychondritis, osteochondritis dissecans and aggrecanopathies by CC administering the novel polypeptide; and a method for preparing the novel CC polypeptide. The present sequence represents an anti-MMP13 ISVD heavy CC chain variable region (VHH), which is used in the invention for treating CC or preventing diseases or disorders associated with MMP13. Note: SEQ ID CC 125 is mentioned in claim 40 but no corresponding sequence is provided in CC the patent. XX SQ Sequence 129 AA; Query Match 73.9%; Score 474.5; Length 129; Best Local Similarity 70.7%; Matches 94; Conservative 6; Mismatches 18; Indels 15; Gaps 2; Qy 1 DVQLVESGGGLVQPGGSLRLSCTASGRTFTNYKSNYKMAWFRQAPGKARAFVGRTDWTGK 60 |||||||||||||||||||||| |||||| |:| | |||||||| | || |:| Db 1 DVQLVESGGGLVQPGGSLRLSCAASGRTF----SSYAMGWFRQAPGKEREFVAAISWSGG 56 Qy 61 SAIIANSVKGRFTISRDNAKNTVYLQMNSLRPEDTAVYYCAAGTT-----------IGQY 109 | |:||||||||||||:||||||||||||||||||||| | :|:| Db 57 STYYADSVKGRFTISRDNSKNTVYLQMNSLRPEDTAVYYCTAALAVYGPNRYRYGPVGEY 116 Qy 110 TYWGQGTLVTVSS 122 |||||||||||| Db 117 NYWGQGTLVTVSS 129 SEQ ID NO:10 BFW75036 ID BFW75036 standard; protein; 278 AA. XX AC BFW75036; XX DT 24-JAN-2019 (first entry) XX DE Anti-MMP13 construct (40E09-517A01 clone 71), SEQ ID 163. XX KW MMP13; Metalloprotease-13; achondroplasia; antiarthritic; KW antibody production; antibody therapy; antiinflammatory; arthritis; KW chondrodystrophy; collagenase; cytostatic; degeneration; diagnostic test; KW dysplasia; gout; growth-disorder-gen.; heavy chain variable region; KW hernia; immuno-diagnosis; joint disease; matrix metalloproteinase 13; KW musculoskeletal-gen.; nanobody; osteoarthritis; osteochondritis; KW osteopathic; polychondritis; prophylactic to disease; KW psoriatic arthritis; rheumatoid arthritis; single domain antibody; KW therapeutic; vulnerary. XX OS Camelidae. OS Synthetic. XX CC PN WO2018220235-A1. XX CC PD 06-DEC-2018. XX CC PF 04-JUN-2018; 2018WO-EP064667. XX PR 02-JUN-2017; 2017EP-00174402. XX CC PA (MERE ) MERCK PATENT GMBH. CC PA (ABLY ) ABLYNX NV. XX CC PI Descamps F, Beste G, Hermans G, Guehring H, Toleikis L, Ladel C; XX DR WPI; 2018-96946V/01. XX CC PT Polypeptide comprises one immunoglobulin single variable domain binding CC PT matrix metalloproteinase, where matrix metalloproteinase is chosen from CC PT the group consisting of collagenase, matrix metalloproteinase-8, matrix CC PT metalloproteinase-l. XX CC PS Claim 43; SEQ ID NO 163; 122pp; English. XX CC The present invention relates to a novel polypeptide useful for treating CC or preventing matrix metalloproteinase (MMP) 13 associated diseases or CC disorders. The polypeptide comprises one immunoglobulin single variable CC domain (ISVD) binding to matrix metalloproteinase, where matrix CC metalloproteinase is selected from MMP13 (collagenase), MMP8 CC (collagenase), MMP1 (collagenase), MMP19 and MMP20 (enamelysin). The CC invention further provides: a method for treating, preventing or CC diagnosing diseases or disorders and its symptoms such as arthropathies CC and chondrodystrophies, arthritic diseases includes osteoarthritis, CC rheumatoid arthritis, gouty arthritis, psoriatic arthritis, traumatic CC rupture or detachment, achondroplasia, costochondritis, CC Spondyloepimetaphyseal dysplasia, spinal disc herniation, lumbar disk CC degeneration disease, degenerative joint disease, and relapsing CC polychondritis, osteochondritis dissecans and aggrecanopathies by CC administering the novel polypeptide; and a method for preparing the novel CC polypeptide. The present sequence represents an anti-MMP13 construct CC comprising two anti-MMP13 ISVD heavy chain variable regions (VHHs) linked CC via a linker, which is used in the invention for treating or preventing CC diseases or disorders associated with MMP13. Note: SEQ ID 125 is CC mentioned in claim 40 but no corresponding sequence is provided in the CC patent. XX SQ Sequence 278 AA; Query Match 73.0%; Score 468.5; Length 278; Best Local Similarity 69.9%; Matches 93; Conservative 6; Mismatches 19; Indels 15; Gaps 2; Qy 1 EVQLVESGGGLVQPGGSLRLSCTASGRTFTNYKSNYKMAWFRQAPGKARAFVGRTDWTGN 60 |||||||||||||||||||||| |||||| |:| | |||||||| | || |:| Db 150 EVQLVESGGGLVQPGGSLRLSCAASGRTF----SSYAMGWFRQAPGKEREFVAAISWSGG 205 Qy 61 SAIIANSVKDRFTISRDNAKNTVYLQMNSLRPEDTAVYYCAAGTT-----------IGQY 109 | |:||| ||||||||:||||||||||||||||||||| | :|:| Db 206 STYYADSVKGRFTISRDNSKNTVYLQMNSLRPEDTAVYYCTAALAVYGPNRYRYGPVGEY 265 Qy 110 TYWGQGTLVTVSS 122 |||||||||||| Db 266 NYWGQGTLVTVSS 278 WO2021156490 teaches a humanized anti-S protein VH comprising SEQ ID NO:11, which is 73.4% identical to instant SEQ ID NO:10 (see the sequence alignment below). SEQ ID NO:10 BJT36748 ID BJT36748 standard; protein; 125 AA. XX AC BJT36748; XX DT 16-SEP-2021 (first entry) XX DE Humanized anti-S protein antibody heavy chain variable region, SEQ ID 11. XX KW S protein; antibody therapy; coronavirus infection; diagnostic test; KW heavy chain variable region; humanized antibody; imaging; KW immuno-diagnosis; immunoassay; mutein; prophylactic to disease; KW protein detection; respiratory-gen.; sars coronavirus infection; KW spike protein; therapeutic; virucide; virus-like particle. XX OS Lama glama. OS Synthetic. XX CC PN WO2021156490-A2. XX CC PD 12-AUG-2021. XX CC PF 05-FEB-2021; 2021WO-EP052885. XX PR 06-FEB-2020; 2020US-0971013P. PR 12-MAR-2020; 2020US-0988610P. PR 18-MAR-2020; 2020US-0991408P. PR 19-JUN-2020; 2020US-0041240P. PR 25-SEP-2020; 2020WO-EP077004. PR 23-DEC-2020; 2020GB-00020508. PR 13-JAN-2021; 2021EP-00151356. XX CC PA (VIBV ) VIB VZW. CC PA (UGNT ) UNIV GENT. CC PA (USSH ) US DEPT HEALTH & HUMAN SERVICES. CC PA (TEXA ) UNIV TEXAS SYSTEM. CC PA (EXEV-) EXEVIR BIO BV. CC PA (DARC ) DARTMOUTH COLLEGE. CC PA (UYLN ) UNIV KATHOLIEKE LEUVEN KU LEUVEN R & D. CC PA (ULBR ) UNIV VRIJE BRUSSEL. XX CC PI Schepens B, Saelens X, Callewaert N, De Vlieger D, Van Schie L; CC PI Nerinckx W, Roose K, Van Breedam W, Eeckhaut H, Fijalkowska D; CC PI Lonigro C, De Cae S, Dombrecht B, Stortelers C, Neyts J, Delang L; CC PI Kaptein S, Duarte Da Rocha Pereira J, Graham B, Mclellan J, Wrapp D; CC PI Remaut H; XX DR WPI; 2021-93399V/071. XX CC PT Binding agent specifically binding corona virus spike protein as CC PT medicament and diagnostic, in in-vivo imaging, prophylactic or CC PT therapeutic treatment with coronavirus infection, comprises amino acid CC PT residues Leu355, Tyr356 and Ser358. XX CC PS Claim 8; SEQ ID NO 11; 220pp; English. XX CC The present invention relates to a novel binding agent specifically CC binding to the coronavirus spike protein, useful in preparing a CC medicament for treating and preventing coronavirus infection. The binding CC agent specifically binds to the coronavirus spike protein comprising CC amino acid residues L355, Y356, S358, S362, T363, F364, K365, C366 and CC Y494 of BJT36761. The invention also provides: a nucleic acid molecule CC encoding the binding agent; a recombinant vector comprising the nucleic CC acid molecule; a complex comprising a receptor binding domain of SARS- CC Corona virus encoding nucleotides of BJT36762 and BJT36763 and the CC binding agent; a host cell comprising the binding agent, nucleic acid CC molecule, recombinant vector or complex; a pharmaceutical composition CC comprising the binding agent, nucleic acid molecule or recombinant vector CC ; and the use of the binding agent for (a) detecting a viral particle or CC a viral spike protein from a virus selected from the group of viruses CC belonging to clade 1a, 1b, 2 and/or 3 of bat SARS-related sarbecoviruses, CC and SARS-Cov-2, GD-Pangolin, RaTG13, WIV1, LYRall, RsSHCOM, Rs7327, SARS- CC CoV-1, Rs4231, Rs4084, Rp3, HKU3-1 or BM48-31 viruses, and (b) diagnosing CC sarbecoviruses such as SARS-CoV-2 viruses, and in-vivo imaging purposes. XX SQ Sequence 125 AA; Query Match 73.4%; Score 471.5; Length 125; Best Local Similarity 74.4%; Matches 96; Conservative 4; Mismatches 18; Indels 11; Gaps 3; Qy 1 EVQLVESGGGLVQPGGSLRLSCTASGRTFTNYKSNYKMAWFRQAPGKARAFVGRTDWTGN 60 |||||||||||||||||||||| |||||| | | | |||||||| | || |:| Db 1 EVQLVESGGGLVQPGGSLRLSCAASGRTF----SEYAMGWFRQAPGKEREFVATISWSGG 56 Qy 61 SAIIANSVKDRFTISRDNAKNTVYLQMNSLRPEDTAVYYCAA---GTTIGQ----YTYWG 113 | |:||| |||||||||||||||||||||||||||||||| || : : | ||| Db 57 STYYADSVKGRFTISRDNAKNTVYLQMNSLRPEDTAVYYCAAAGLGTVVSEWDYDYDYWG 116 Qy 114 QGTLVTVSS 122 ||||||||| Db 117 QGTLVTVSS 125 11. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a). A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action. 12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHANG-YU WANG whose telephone number is (571)272-4521. The examiner can normally be reached Monday-Thursday, 7:00am-5:00pm EST. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached at 571-272-0911. 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. Chang-Yu Wang October 6, 2026 /CHANG-YU WANG/Primary Examiner, Art Unit 1675