DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
1. Claims 1, 2, 7, 12-15, 17-21, 23, 25, and 28-33 as amended on November 06, 2024 are pending and under consideration.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
2. Claim(s) 1, 2, 7, 12, 13, 23, 25, and 28-33 are rejected under 35 U.S.C. 103 as being unpatentable over US 2016/0046717 A1 (Sheppard et al. Feb. 18, 2016), “Sheppard” in view of Shihan et al. (Investigative Ophthalmology & Visual Science June 2020, Vol.61, 3986), “Shihan” and in view of US 2011/0223177 A1 (Wormstone et al. Sep. 15, 2011), “Wormstone”.
Sheppard teaches antibodies that specifically bind to human integrin β8 and inhibit adhesion of latency associated peptide (LAP) to αvβ8 are provided. Sheppard teaches the antibody cross-reacts with mouse integrin β8. Sheppard teaches the antibody blocks TGF-b activation. In some embodiments, the antibody antagonizes binding of LAP to αVβ8 with an IC50 5 nM. See abstract and claims 1-4.
Sheppard teaches the integrin β8 antibodies ADAW-2 and ADAW-16 comprising SEQ ID NOs: 1 (VH) and 16 (VL). See Table 1, pp. 11-12.
SEQ ID NO: 1 of Sheppard comprises the claimed VH sequences of SEQ ID NOs: 6, 2, 3 and 18. See Appendix.
SEQ ID NO: 16 of Sheppard comprises the claimed VL sequences of SEQ ID NOs: 14, 9, 10 and 25. See Appendix.
Sheppard teaches that ADAW-2 and ADAW-16 antibodies can be monoclonal or humanized with a human framework region. See ¶¶ 0010, 0080, 0114, 0115, and 0118.
Sheppard teaches that ADAW-2 and ADAW-16 antibodies cross react with murine β8, block LAP binding to αVβ8, and block TGF-b activation. See ¶¶ 0017, 0021, 0023, 0025, and 0026, Example 1 and Figs. 4, 8, 10, 12 and 13.
Sheppard teaches the antibodies of the invention are used for treating or preventing diseases for which decrease of TGF-β activation has an ameliorative effect in humans. See ¶¶ 0012, 0076 and 0123-0149 and claim 13.
Sheppard teaches as set forth above, but does not teach treating or preventing posterior capsular opacification (PCO) in a human after ocular lens replacement.
Shihan teaches fibrotic posterior capsular opacification (PCO), the major post cataract surgery (PCS) complication, is driven by transforming growth factor-β (TGF-β) signaling.
Shihan teaches that aV-integrins are critical for the activation of TGFβ signaling in fibrotic PCO pathogenesis.
Shihan teaches mice lacking integrin β8 by knockout did not undergo a fibrotic response post cataract surgery (PCS), which was associated with loss of TGFβ signaling.
Shihan teaches that the αVβ8 blocking antibody ADAW-11 blocks TGFβ signaling and undergo a fibrotic response 3-5 days post cataract surgery (PCS).
Shihan teaches a blocking αVβ8 integrin function can prevent lens epithelial cells (LC) fibrosis post cataract (PCS). surgery as it ameliorates TGFβ activation and fibrotic response by LCs PCS. Shihan teaches these results suggest that ADWA-11 or related αVβ8 integrin function blocking reagents could be effective therapeutics preventing PCO development.
Wormstone teaches inhibitors of myosin activity are used to treat or prevent a fibrotic disorder of the eye, for example posterior capsule opacification (PCO). See abstract.
Wormstone teaches fibrotic disorders of the eye are common complications arising from surgical treatment of disorders including glaucoma, pterygia and cataract. Wormstone teaches PCO is the most common fibrotic complication following cataract or other ocular lens replacement surgery. See ¶ 0002.
Wormstone teaches TGFβ has been implicated in a number of fibrotic disorders of the lens including PCO. See ¶¶ 0003-0004.
Wormstone teaches for treatment or prevention of fibrotic complications of ocular lens replacement surgery, for example cataract surgery, the administration of the active agent and composition of the present invention is suitably by irrigation and/or by association with the lens and/or the capsular bag and/or its vicinity, or by administration by direct infusion or injection into the capsular bag and/or its vicinity. See ¶¶ 0027-0030.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Sheppard, Shihan and Wormstone and treat or prevent posterior capsular opacification (PCO) in a human after ocular lens replacement using the human integrin β8 antibodies, like ADAW-2 and ADAW-16, of Sheppard because Sheppard teaches the antibodies block LAP binding to αVβ8 and block TGF-b activation, Sheppard teaches the antibodies of the invention are used for treating or preventing diseases for which decrease of TGF-β activation has an ameliorative effect in humans, Shihan teaches a blocking αVβ8 integrin function can prevent lens epithelial cells (LC) fibrosis post cataract (PCS) surgery as it ameliorates TGFβ activation and fibrotic response by LCs PC, Shihan suggest that ADWA-11 αVβ8 integrin blocking antibody or related αVβ8 integrin function blocking reagents could be effective therapeutics preventing PCO development, and Wormstone teaches PCO is the most common fibrotic complication following cataract or other ocular lens replacement surgery and Wormstone teaches TGFβ has been implicated in a number of fibrotic disorders of the lens including PCO. Thus given the importance TGFβ in PCO, the ability of the integrin β8 antibodies of Sheppard to block TGFβ, the PCO inhibitory activity of the αVβ8 integrin blocking antibody of Shihan and given that PCO is common after lens replacement surgery, one would have been motivated to use the human integrin β8 antibodies, like ADAW-2 and ADAW-16, of Sheppard to treat or prevent posterior capsular opacification (PCO) in a human after ocular lens replacement by administering the integrin β8 antibodies to the surgically treated eye.
Additionally, regarding claims 30-32, one would have been motivated to optimize the timing of administration of integrin β8 antibodies to achieve the optimal response.
3. Claim(s) 14 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over US 2016/0046717 (Sheppard et al. Feb. 18, 2016), “Sheppard” in view of Shihan et al. (Investigative Ophthalmology & Visual Science June 2020, Vol.61, 3986), “Shihan” and in view of US 2011/0223177 (Wormstone et al. Sep. 15, 2011), “Wormstone” as applied to claims 1, 2, 7, 12, 13, 23, 25, and 28-33 above, and further in view of US 2012/0121585 A1 (Heusser et al. May 17, 2012), “Heusser”.
Sheppard, Shihan and Wormstone teach as set forth above, but do not teach an Fc polypeptide having at least 90% identity to a sequence of any one of SEQ ID NOs: 47-50 or wherein the Fc polypeptide comprises substitutions L234A and L235A and/or the amino acid substitution N297A.
Heusser teaches silent Fc variants of anti-CD40 antibodies. See abstract and ¶¶ 0002 and 0052-0054.
Heusser teaches that the silent Fc antibodies exhibit no or low antibody-dependent cellular cytotoxicity (ADCC) activity. See ¶¶ 0051-0053.
Heusser teaches examples of silent Fc IgG1 antibodies comprise the so-called LALA mutant comprising L234A and L235A mutation in the IgG1 Fc amino acid sequence or the N297A mutation.
Heusser teaches the Fc domain of SEQ ID NO: 19 comprising the L234A and L235A mutations. See ¶¶ 0065 and Table 2. The Fc domain of SEQ ID NO: 19 of Heuser comprises the claimed SEQ ID NO: 48. See Appendix.
Heusser teaches the Fc domain of SEQ ID NO: 17 comprising the N297A mutation. See ¶¶ 0065 and Table 2. The Fc domain of SEQ ID NO: 17 of Heuser comprises the claimed SEQ ID NO: 50. See Appendix.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Sheppard, Shihan, Wormstone and Heusser and use the silent Fc domains of Heusser in the integrin β8 antibodies of Sheppard to reduce or eliminate ADCC activity of the antibodies used for treating or preventing posterior capsular opacification (PCO). One would have been motivated to use the silent Fc domains of Heusser in the integrin β8 antibodies to reduce the immune response directed against the administered antibodies to reduce side effects, such as toxicity, of the treatment to improve the therapy.
4. Claim(s) 1, 2, 7, 12, 13, 23, 25, and 28-33 are rejected under 35 U.S.C. 103 as being unpatentable over US 2016/0046717 A1 (Sheppard et al. Feb. 18, 2016), “Sheppard” in view of Duncan et al. (Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6449), “Duncan” and in view of US 2011/0223177 A1 (Wormstone et al. Sep. 15, 2011), “Wormstone”.
Sheppard teaches as set forth above, but does not teach treating or preventing posterior capsular opacification (PCO) in a human after ocular lens replacement.
Duncan teaches fibrotic posterior capsular opacification (PCO), the major post cataract surgery (PCS) complication, is driven by transforming growth factor-β (TGF-β) signaling.
Duncan teaches that aV-integrins are critical for fibrotic PCO pathogenesis.
Duncan teaches mice lacking integrin β8 by knockout did not undergo a fibrotic response post cataract surgery (PCS), which was associated with loss of TGFβ signaling.
Duncan teaches our data suggest that aVβ8 integrin is the main aV- integrin heterodimer mediating fibrotic PCO. Further, we have identified a possible critical role for aVβ8 integrin in the regulation of post cataract surgical inflammation. As aVβ8 integrin is a "druggable" target, the outcome of this study suggests effective therapeutics to prevent fibrotic PCO.
Wormstone teaches as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Sheppard, Duncan and Wormstone and treat or prevent posterior capsular opacification (PCO) in a human after ocular lens replacement using the human integrin β8 antibodies, like ADAW-2 and ADAW-16, of Sheppard because Sheppard teaches the antibodies block LAP binding to αVβ8 and block TGF-b activation, Sheppard teaches the antibodies of the invention are used for treating or preventing diseases for which decrease of TGF-β activation has an ameliorative effect in humans, Duncan teaches that aVβ8 integrin is the main aV- integrin heterodimer mediating fibrotic PCO and aVβ8 integrin is a "druggable" target to prevent fibrotic PCO and Wormstone teaches PCO is the most common fibrotic complication following cataract or other ocular lens replacement surgery and Wormstone teaches TGFβ has been implicated in a number of fibrotic disorders of the lens including PCO. Thus given the importance TGFβ in PCO, the ability of the integrin β8 antibodies of Sheppard to block TGFβ, given that aVβ8 integrin has a critical role in the regulation of post cataract surgical inflammation and PCO and given that PCO is common after lens replacement surgery, one would have been motivated to use the human integrin β8 antibodies, like ADAW-2 and ADAW-16, of Sheppard to treat or prevent posterior capsular opacification (PCO) in a human after ocular lens replacement by administering the integrin β8 antibodies to the surgically treated eye.
Additionally, regarding claims 30-32, one would have been motivated to optimize the timing of administration of integrin β8 antibodies to achieve the optimal treatment.
5. Claim(s) 14 and 15 are rejected under 35 U.S.C. 103 as being unpatentable over US 2016/0046717 (Sheppard et al. Feb. 18, 2016), “Sheppard” in view of Duncan et al. (Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6449), “Duncan” and in view of US 2011/0223177 (Wormstone et al. Sep. 15, 2011), “Wormstone” as applied to claims 1, 2, 7, 12, 13, 23, 25, and 28-33 above, and further in view of US 2012/0121585 A1 (Heusser et al. May 17, 2012), “Heusser”.
Sheppard, Duncan and Wormstone teach as set forth above, but do not teach an Fc polypeptide having at least 90% identity to a sequence of any one of SEQ ID NOs: 47-50 or wherein the Fc polypeptide comprises substitutions L234A and L235A and/or the amino acid substitution N297A.
Heusser teaches as set forth above
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of Sheppard, Duncan, Wormstone and Heusser and use the silent Fc domains of Heusser in the integrin β8 antibodies of Sheppard to reduce or eliminate ADCC activity of the antibodies used for treating or preventing posterior capsular opacification (PCO). One would have been motivated to use the silent Fc domains of Heusser in the integrin β8 antibodies to reduce the immune response directed against the administered antibodies to reduce side effects, such as toxicity, of the treatment to improve the therapy.
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.
6. Claims 1, 2, 7, 12, 13, 23, 25, and 28-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 9,969,804 B2 (Sheppard et al. May 15, 2018) in view of US 2016/0046717 (Sheppard et al. Feb. 18, 2016), “Sheppard”, Duncan et al. (Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6449), “Duncan” and of US 2011/0223177 A1 (Wormstone et al. Sep. 15, 2011), “Wormstone”.
The ’804 claims are drawn to, in part,
1. An isolated antibody that specifically binds to human integrin β8 and inhibits adhesion of latency associated peptide (LAP) to αvβ8, wherein the antibody comprises: a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:1 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16; or a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:2 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16; or a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:3 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16.
2. The antibody of claim 1, wherein the antibody comprises one or more human framework regions.
3. A pharmaceutical composition comprising the antibody of claim 1.
4. The isolated antibody of claim 1, wherein HCDR1 comprises SEQ ID NO:88, HCDR2 comprises SEQ ID NO:90, and HCDR3 comprises SEQ ID NO:25, and LCDR1 comprises SEQ ID NO:46, LCDR2 comprises SEQ ID NO:47, and LCDR3 comprises SEQ ID NO:48.
5. The isolated antibody of claim 1, wherein HCDR1 comprises SEQ ID NO:89, HCDR2 comprises SEQ ID NO:24, and HCDR3 comprises SEQ ID NO:25, and LCDR1 comprises SEQ ID NO:46, LCDR2 comprises SEQ ID NO:47, and LCDR3 comprises SEQ ID NO:48.
6. The isolated antibody of claim 1, wherein HCDR1 comprises SEQ ID NO:88, HCDR2 comprises SEQ ID NO:90, and HCDR3 comprises SEQ ID NO:25, and LCDR1 comprises SEQ ID NO:46, LCDR2 comprises SEQ ID NO:47, and LCDR3 comprises SEQ ID NO:48.
SEQ ID NO: 1 of the ’804 claims comprises the claims VH sequences of SEQ ID NOs: 6, 2, 3 and 18. See Table 1- ADWA-2 and ADA-16 of ‘804 and the Appendix.
SEQ ID NO: 16 of the ’804 claims comprises the claims VL sequences of SEQ ID NOs: 14, 9, 10 and 25. See Table 1- ADWA-2 and ADA-16 of ‘804 and the Appendix.
The HCDRs and LCDRs of claim 1 and 4-6 are the CDRs of the ADAM-2 and ADAM-16 antibodies which comprise the HCDR SEQ ID NOs: 6, 2, and 3 and LCDR SEQ ID NOs: 14, 9, and 10. See Table 1- ADWA-2 and ADA-16 of ‘804 and the Appendix.
The ’804 claims teach as set forth above, but does not teach treating or preventing posterior capsular opacification (PCO) in a human after ocular lens replacement.
Sheppard, Duncan and Wormstone teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ’804 claims, Sheppard, Duncan and Wormstone and treat or prevent posterior capsular opacification (PCO) in a human after ocular lens replacement using the human integrin β8 antibodies, like ADAW-2 and ADAW-16, of the ‘804 claims and Sheppard because Sheppard teaches the antibodies block LAP binding to αVβ8 and block TGF-b activation, Sheppard teaches the antibodies of the invention are used for treating or preventing diseases for which decrease of TGF-β activation has an ameliorative effect in humans, Duncan teaches that aVβ8 integrin is the main aV- integrin heterodimer mediating fibrotic PCO aVβ8 integrin is a "druggable" target to prevent fibrotic PCO and Wormstone teaches PCO is the most common fibrotic complication following cataract or other ocular lens replacement surgery and Wormstone teaches TGFβ has been implicated in a number of fibrotic disorders of the lens including PCO. Thus given the importance TGFβ in PCO, the ability of the integrin β8 antibodies of the ‘804 claims and Sheppard to block TGFβ, aVβ8 integrin has a critical role in the regulation of post cataract surgical inflammation and PCO and given that PCO is common after lens replacement surgery, one would have been motivated to use the human integrin β8 antibodies, like ADAW-2 and ADAW-16, of the ‘804 claims and Sheppard to treat or prevent posterior capsular opacification (PCO) in a human after ocular lens replacement by administering the integrin β8 antibodies to the surgically treated eye.
Additionally, regarding claims 30-32, one would have been motivated to optimize the timing of administration of integrin β8 antibodies to achieved the optimal response.
7. Claims 14 and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 9,969,804 B2 (Sheppard et al. May 15, 2018) in view of US 2016/0046717 (Sheppard et al. Feb. 18, 2016), “Sheppard”¸ Duncan et al. (Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6449), “Duncan” and in view of US 2011/0223177 A1 (Wormstone et al. Sep. 15, 2011), “Wormstone” as applied to claims 1, 2, 7, 12, 13, 23, 25, and 28-33 above, and further in view of US 2012/0121585 A1 (Heusser et al. May 17, 2012), “Heusser”.
The ’804 claims, Sheppard, Duncan and Wormstone teach as set forth above, but do not teach an Fc polypeptide having at least 90% identity to a sequence of any one of SEQ ID NOs: 47-50 or wherein the Fc polypeptide comprises substitutions L234A and L235A and/or the amino acid substitution N297A.
Heusser teaches as set forth above
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ’804 claims, Sheppard, Duncan, Wormstone and Heusser and use the silent Fc domains of Heusser in the integrin β8 antibodies of Sheppard to reduce or eliminate ADCC activity of the antibodies used for treating or preventing posterior capsular opacification (PCO). One would have been motivated to use the silent Fc domains of Heusser in the integrin β8 antibodies to reduce the immune response directed against the administered antibodies to reduce side effects, such as toxicity, of the treatment to improve the therapy.
8. Claims 1, 2, 7, 12, 13, 23, 25, and 28-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 19-21 of U.S. Patent No. 10,597,455 B2 (Sheppard et al. March 24, 2020) in view of US 2016/0046717 (Sheppard et al. Feb. 18, 2016), “Sheppard”, Duncan et al. (Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6449), “Duncan” and of US 2011/0223177 A1 (Wormstone et al. Sep. 15, 2011), “Wormstone”.
The ’455 claims are drawn to, in part,
1. An isolated nucleic acid encoding an antibody that specifically binds to human integrin β8 and inhibits adhesion of latency associated peptide (LAP) to αvβ8, wherein the antibody comprises: a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:1 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16; or a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:2 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16; or a heavy chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (HCDR1, HCDR2, and HCDR3) of SEQ ID NO:3 and a light chain variable region comprising the Kabat-determined or Chothia-determined complementarity determining regions (LCDR1, LCDR2, and LCDR3) of SEQ ID NO:16.
2. The isolated nucleic acid of claim 1, wherein the antibody comprises one or more human framework regions.
3. The isolated nucleic acid of claim 1, wherein HCDR1 comprises SEQ ID NO:88, HCDR2 comprises SEQ ID NO:90, and HCDR3 comprises SEQ ID NO:25, and LCDR1 comprises SEQ ID NO:46, LCDR2 comprises SEQ ID NO:47, and LCDR3 comprises SEQ ID NO:48.
4. The isolated nucleic acid of claim 1, wherein HCDR1 comprises SEQ ID NO:89, HCDR2 comprises SEQ ID NO:24, and HCDR3 comprises SEQ ID NO:25, and LCDR1 comprises SEQ ID NO:46, LCDR2 comprises SEQ ID NO:47, and LCDR3 comprises SEQ ID NO:48.
5. The isolated nucleic acid of claim 1, wherein HCDR1 comprises SEQ ID NO:89, HCDR2 comprises SEQ ID NO:26, and HCDR3 comprises SEQ ID NO:25, and LCDR1 comprises SEQ ID NO:46, LCDR2 comprises SEQ ID NO:47, and LCDR3 comprises SEQ ID NO:48.
19. The isolated nucleic acid of claim 1, wherein the nucleic acid comprises any of SEQ ID NOS: 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84, 85, 86, or 87.
20. An expression vector comprising the nucleic acid of claim 1.
21. An isolated host cell comprising the vector of claim 19.
SEQ ID NO: 1 of the ’455 claims comprises the claims VH sequences of SEQ ID NOs: 6, 2, 3 and 18. See Table 1- ADWA-2 and ADA-16 of ’455 and the Appendix.
SEQ ID NO: 16 of the ’455 claims comprises the claims VL sequences of SEQ ID NOs: 14, 9, 10 and 25. See Table 1- ADWA-2 and ADA-16 of ’455 and the Appendix.
The HCDRs and LCDRs of claim 1 and 4-6 are the CDRs of the ADAM-2 and ADAM-16 antibodies which comprise the HCDR SEQ ID NOs: 6, 2, and 3 and LCDR SEQ ID NOs: 14, 9, and 10. See Table 1- ADWA-2 and ADA-16 of ’455 and the Appendix.
The ’455 claims teach as set forth above, but do not teach treating or preventing posterior capsular opacification (PCO) in a human after ocular lens replacement with an antibody that specifically binds to human integrin β8.
Sheppard, Duncan and Wormstone teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ’455 claims, Sheppard, Duncan and Wormstone and treat or prevent posterior capsular opacification (PCO) in a human after ocular lens replacement using the human integrin β8 antibodies, like ADAW-2 and ADAW-16, of the ’455 claims and Sheppard because Sheppard teaches the antibodies block LAP binding to αVβ8 and block TGF-b activation, Sheppard teaches the antibodies of the invention are used for treating or preventing diseases for which decrease of TGF-β activation has an ameliorative effect in humans, Duncan teaches that aVβ8 integrin is the main aV- integrin heterodimer mediating fibrotic PCO aVβ8 integrin is a "druggable" target to prevent fibrotic PCO and Wormstone teaches PCO is the most common fibrotic complication following cataract or other ocular lens replacement surgery and Wormstone teaches TGFβ has been implicated in a number of fibrotic disorders of the lens including PCO. Thus given the importance TGFβ in PCO, the ability of the integrin β8 antibodies of the ’455 claims and Sheppard to block TGFβ, aVβ8 integrin has a critical role in the regulation of post cataract surgical inflammation and PCO and given that PCO is common after lens replacement surgery, one would have been motivated to use the human integrin β8 antibodies, like ADAW-2 and ADAW-16, of the ’455 claims and Sheppard to treat or prevent posterior capsular opacification (PCO) in a human after ocular lens replacement by administering the integrin β8 antibodies to the surgically treated eye.
Additionally, regarding claims 30-32, one would have been motivated to optimize the timing of administration of integrin β8 antibodies to achieved the optimal response.
9. Claims 14 and 15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 and 19-21 of U.S. Patent No. 10,597,455 B2 (Sheppard et al. March 24, 2020) in view of US 2016/0046717 (Sheppard et al. Feb. 18, 2016), “Sheppard”¸ Duncan et al. (Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6449), “Duncan” and in view of US 2011/0223177 A1 (Wormstone et al. Sep. 15, 2011), “Wormstone” as applied to claims 1, 2, 7, 12, 13, 23, 25, and 28-33 above, and further in view of US 2012/0121585 A1 (Heusser et al. May 17, 2012), “Heusser”.
The ’455 claims, Sheppard, Duncan and Wormstone teach as set forth above, but do not teach an Fc polypeptide having at least 90% identity to a sequence of any one of SEQ ID NOs: 47-50 or wherein the Fc polypeptide comprises substitutions L234A and L235A and/or the amino acid substitution N297A.
Heusser teaches as set forth above
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ’455 claims, Sheppard, Duncan, Wormstone and Heusser and use the silent Fc domains of Heusser in the integrin β8 antibodies of Sheppard to reduce or eliminate ADCC activity of the antibodies used for treating or preventing posterior capsular opacification (PCO). One would have been motivated to use the silent Fc domains of Heusser in the integrin β8 antibodies to reduce the immune response directed against the administered antibodies to reduce side effects, such as toxicity, of the treatment to improve the therapy.
10. Claims 1, 2, 7, 12-15, 17-21, 23, 25, and 28-33 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 7, 12-15, 17-21, 23, 25, and 29-33 of co-pending Application No. 18/274, 069 (published as US 2024/0425601 A1 in view of US 2016/0046717 (Sheppard et al. Feb. 18, 2016), “Sheppard”, Duncan et al. (Investigative Ophthalmology & Visual Science July 2019, Vol.60, 6449), “Duncan” and of US 2011/0223177 A1 (Wormstone et al. Sep. 15, 2011), “Wormstone”.
The ’069 claims are drawn to
1. An isolated antibody that specifically binds to human integrin β8 and inhibits adhesion of latency associated peptide (LAP) to αvβ8, wherein the isolated antibody comprises: (1) a heavy chain complementary determining region 1 (HCDR1) having a sequence of any one of SEQ ID NOS:1, 5, and 6; (2) an HCDR2 having a sequence of any one of SEQ ID NOS:2, 4, and 7; (3) an HCDR3 having the sequence of SEQ ID NO:3; (4) a light chain complementary determining region 1 (LCDR1) having a sequence of any one of SEQ ID NOS:8, 11, 13, and 14; (5) a LCDR2 having a sequence of any one of SEQ ID NOS:9 and 12; and (6) a LCDR3 having the sequence of SEQ ID NO:10.
2. The isolated antibody of claim 1, wherein the antibody comprises: (a) an HCDR1 having the sequence of SEQ ID NO:1, an HCDR2 having the sequence of SEQ ID NO: 2, and an HCDR3 having the sequence of SEQ ID NO: 3; or (b) an HCDR1 having the sequence of SEQ ID NO:1, an HCDR2 having the sequence of SEQ ID NO: 4, and an HCDR3 having the sequence of SEQ ID NO: 3; or (c) an HCDR1 having the sequence of SEQ ID NO: 5, an HCDR2 having the sequence of SEQ ID NO: 2, and an HCDR3 having the sequence of SEQ ID NO: 3; or (d) an HCDR1 having the sequence of SEQ ID NO: 6, an HCDR2 having the sequence of SEQ ID NO: 2, and an HCDR3 having the sequence of SEQ ID NO: 3; or (e) an HCDR1 having the sequence of SEQ ID NO:1, an HCDR2 having the sequence of SEQ ID NO: 7, and an HCDR3 having the sequence of SEQ ID NO: 3.
7. The isolated antibody of claim 1, wherein the antibody comprises: (a) a LCDR1 having the sequence of SEQ ID NO: 8, a LCDR2 having the sequence of SEQ ID NO: 9, and a LCDR3 having the sequence of SEQ ID NO: 10; or (b) a LCDR1 having the sequence of SEQ ID NO: 11, a LCDR2 having the sequence of SEQ ID NO: 9, and a LCDR3 having the sequence of SEQ ID NO: 10; or (c) a LCDR1 having the sequence of SEQ ID NO: 8, a LCDR2 having the sequence of SEQ ID NO: 12, and a LCDR3 having the sequence of SEQ ID NO: 10; or (d) a LCDR1 having the sequence of SEQ ID NO: 13, a LCDR2 having the sequence of SEQ ID NO: 12, and a LCDR3 having the sequence of SEQ ID NO: 10; or (e) a LCDR1 having the sequence of SEQ ID NO: 14, a LCDR2 having the sequence of SEQ ID NO: 9, and a LCDR3 having the sequence of SEQ ID NO: 10.
12. The isolated antibody of claim 1, wherein the antibody comprises a heavy chain variable region having at least 90% identity to a sequence of any one of SEQ ID NOS:15-19 and/or a light chain variable region having at least 90% identity to a sequence of any one of SEQ ID NOS:20-25.
14. The isolated antibody of claim 1, wherein the antibody comprises an Fc polypeptide having at least 90% identity to a sequence of any one of SEQ ID NOS:47-50.
15. The isolated antibody of claim 14, wherein the Fc polypeptide comprises amino acid substitutions L234A and L235A and/or the amino acid substitution N297A.
17. The isolated antibody of claim 1, wherein the antibody comprises: (1) an HCDR1 having the sequence of SEQ ID NO: 1; (2) an HCDR2 having the sequence of SEQ ID NO: 4; (3) an HCDR3 having the sequence of SEQ ID NO: 3; (4) a LCDR1 having the sequence of SEQ ID NO: 8; (5) a LCDR2 having the sequence of SEQ ID NO: 12; and (6) a LCDR3 having the sequence of SEQ ID NO: 10.
18. The isolated antibody of claim 17, wherein the antibody comprises a heavy chain variable region having at least 90% identity to the sequence of SEQ ID NO: 16.
19. The isolated antibody of claim 17wherein the antibody comprises a light chain variable region having at least 90% identity to the sequence of SEQ ID NO: 22.
20. The isolated antibody of any one of claims 17 to 19, wherein the antibody comprises an Fc polypeptide having at least 90% identity to a sequence of any one of SEQ ID NOS:47-50.
21. The isolated antibody of claim 20, wherein the Fc polypeptide comprises amino acid substitutions L234A and L235A and/or the amino acid substitution N297A.
23. The isolated antibody of claim 1 , wherein the antibody is a monoclonal antibody and/or a humanized antibody.
25. The isolated antibody of claim 1, wherein the antibody cross-reacts with mouse integrin β8, and/or (b) blocks TGFß activation; and/or (c) antagonizes binding of LAP to avß8 with an IC50 below 5 nM.
32. A pharmaceutical composition comprising the isolated antibody of claim 1 and a pharmaceutically acceptable carrier.
33. A method of reducing TGFβ activation in a human in need thereof, the method comprising administering a therapeutically effective amount of the isolated antibody of claim 1 to the human, thereby reducing TGFβ activation in the human.
The antibody sequences of the’069 claims are the same as currently claimed. See Table 1 of the ‘069 specification and ¶¶ 0115-0118 of the ‘069 specification.
The ’069 claims teach as set forth above, but does not teach treating or preventing posterior capsular opacification (PCO) in a human after ocular lens replacement.
Sheppard, Duncan and Wormstone teach as set forth above.
It would have been prima facie obvious at the time the invention was filed given that the level of skill in the art was high to combine the teachings of the ’069 claims, Sheppard, Duncan and Wormstone and treat or prevent posterior capsular opacification (PCO) in a human after ocular lens replacement using the human integrin β8 antibodies, like ADAW-2 and ADAW-16, of the ’069 claims and Sheppard because Sheppard teaches the antibodies block LAP binding to αVβ8 and block TGF-b activation, Sheppard teaches the antibodies of the invention are used for treating or preventing diseases for which decrease of TGF-β activation has an ameliorative effect in humans, Duncan teaches that aVβ8 integrin is the main aV- integrin heterodimer mediating fibrotic PCO aVβ8 integrin is a "druggable" target to prevent fibrotic PCO and Wormstone teaches PCO is the most common fibrotic complication following cataract or other ocular lens replacement surgery and Wormstone teaches TGFβ has been implicated in a number of fibrotic disorders of the lens including PCO. Thus given the importance TGFβ in PCO, the ability of the integrin β8 antibodies of the ’069 claims and Sheppard to block TGFβ, aVβ8 integrin has a critical role in the regulation of post cataract surgical inflammation and PCO and given that PCO is common after lens replacement surgery, one would have been motivated to use the human integrin β8 antibodies, like ADAW-2 and ADAW-16, of the ’069 claims and Sheppard to treat or prevent posterior capsular opacification (PCO) in a human after ocular lens replacement by administering the integrin β8 antibodies to the surgically treated eye.
Additionally, regarding claims 30-32, one would have been motivated to optimize the timing of administration of integrin β8 antibodies to achieved the optimal response.
This is a provisional nonstatutory double patenting rejection.
Conclusion
11. No claims allowed.
12. Any inquiry concerning this communication or earlier communications from the examiner should be directed to PETER J REDDIG whose telephone number is (571)272-9031. The examiner can normally be reached M-F 8:30-5:30 Eastern Time.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Greg 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.
/PETER J REDDIG/Primary Examiner, Art Unit 1646
APPENDIX
Alignment of SEQ ID NOs: 6, 2, and 3 with SEQ ID NO: 1 of Sheppard
Sequence 1, US/14778997
Publication No. US20160046717A1
GENERAL INFORMATION
APPLICANT: The Regents of the University of California, a California
APPLICANT: corporation
APPLICANT: Sheppard, Dean
APPLICANT: Atakilit, Amha
APPLICANT: Henderson, Neil C.
TITLE OF INVENTION: Methods and Compositions for Treating and Preventing Disease
TITLE OF INVENTION: Associated With alpha-v beta-8 Integrin
FILE REFERENCE: 081906-0958641
CURRENT APPLICATION NUMBER: US/14/778,997
CURRENT FILING DATE: 2015-09-21
PRIOR APPLICATION NUMBER: PCT/US2014/032550
PRIOR FILING DATE: 2014-04-01
PRIOR APPLICATION NUMBER: US 61/807,195
PRIOR FILING DATE: 2013-04-01
NUMBER OF SEQ ID NOS: 87
SEQ ID NO 1
LENGTH: 117
TYPE: PRT
ORGANISM: Mus Musculus
Query Match 86.6%; Score 161.9; Length 117;
Best Local Similarity 38.1%;
Matches 32; Conservative 1; Mismatches 0; Indels 51; Gaps 2;
Qy 1 KASGYTFSSYWIY--------------YIXPTTGYTE----------------------- 23
||||||||||||| ||:|||||||
Db 23 KASGYTFSSYWIYWVKQRPGQGLEWIGYINPTTGYTEYNQKFRDKATLTADKSSNTAYMQ 82
Qy 24 --------------ATEGGNWEDY 33
||||||||||
Db 83 LSSLTSEDSAVYYCATEGGNWEDY 106
Alignment of SEQ ID NO: 18 with SEQ ID NO: 1 of Sheppard
Sequence 1, US/14778997
Publication No. US20160046717A1
GENERAL INFORMATION
APPLICANT: The Regents of the University of California, a California
APPLICANT: corporation
APPLICANT: Sheppard, Dean
APPLICANT: Atakilit, Amha
APPLICANT: Henderson, Neil C.
TITLE OF INVENTION: Methods and Compositions for Treating and Preventing Disease
TITLE OF INVENTION: Associated With alpha-v beta-8 Integrin
FILE REFERENCE: 081906-0958641
CURRENT APPLICATION NUMBER: US/14/778,997
CURRENT FILING DATE: 2015-09-21
PRIOR APPLICATION NUMBER: PCT/US2014/032550
PRIOR FILING DATE: 2014-04-01
PRIOR APPLICATION NUMBER: US 61/807,195
PRIOR FILING DATE: 2013-04-01
NUMBER OF SEQ ID NOS: 87
SEQ ID NO 1
LENGTH: 117
TYPE: PRT
ORGANISM: Mus Musculus
Query Match 100.0%; Score 633; Length 117;
Best Local Similarity 100.0%;
Matches 117; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLQQSGAELAKPGASMKMSCKASGYTFSSYWIYWVKQRPGQGLEWIGYINPTTGYTEY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLQQSGAELAKPGASMKMSCKASGYTFSSYWIYWVKQRPGQGLEWIGYINPTTGYTEY 60
Qy 61 NQKFRDKATLTADKSSNTAYMQLSSLTSEDSAVYYCATEGGNWEDYWGQGTTLTVSS 117
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NQKFRDKATLTADKSSNTAYMQLSSLTSEDSAVYYCATEGGNWEDYWGQGTTLTVSS 117
Alignment of SEQ ID NOs: 14, 9, and 10 with SEQ ID NO: 16 of Sheppard
Sequence 16, US/14778997
Publication No. US20160046717A1
GENERAL INFORMATION
APPLICANT: The Regents of the University of California, a California
APPLICANT: corporation
APPLICANT: Sheppard, Dean
APPLICANT: Atakilit, Amha
APPLICANT: Henderson, Neil C.
TITLE OF INVENTION: Methods and Compositions for Treating and Preventing Disease
TITLE OF INVENTION: Associated With alpha-v beta-8 Integrin
FILE REFERENCE: 081906-0958641
CURRENT APPLICATION NUMBER: US/14/778,997
CURRENT FILING DATE: 2015-09-21
PRIOR APPLICATION NUMBER: PCT/US2014/032550
PRIOR FILING DATE: 2014-04-01
PRIOR APPLICATION NUMBER: US 61/807,195
PRIOR FILING DATE: 2013-04-01
NUMBER OF SEQ ID NOS: 87
SEQ ID NO 16
LENGTH: 107
TYPE: PRT
ORGANISM: Mus musculus
Query Match 82.9%; Score 119.4; Length 107;
Best Local Similarity 37.8%;
Matches 28; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 RASQDISNYLN--------------YYTSRLYS--------------------------- 19
||||||||||| ||||||||
Db 24 RASQDISNYLNWYQQKPDGTVKLLIYYTSRLYSGVPSRFSGSGSGTDYSLTISNLEPKDI 83
Qy 20 -----QQFSELPRT 28
|||||||||
Db 84 ATYYCQQFSELPRT 97
Alignment of SEQ ID NO: 25 with SEQ ID NO: 16 of Sheppard
Sequence 16, US/14778997
Publication No. US20160046717A1
GENERAL INFORMATION
APPLICANT: The Regents of the University of California, a California
APPLICANT: corporation
APPLICANT: Sheppard, Dean
APPLICANT: Atakilit, Amha
APPLICANT: Henderson, Neil C.
TITLE OF INVENTION: Methods and Compositions for Treating and Preventing Disease
TITLE OF INVENTION: Associated With alpha-v beta-8 Integrin
FILE REFERENCE: 081906-0958641
CURRENT APPLICATION NUMBER: US/14/778,997
CURRENT FILING DATE: 2015-09-21
PRIOR APPLICATION NUMBER: PCT/US2014/032550
PRIOR FILING DATE: 2014-04-01
PRIOR APPLICATION NUMBER: US 61/807,195
PRIOR FILING DATE: 2013-04-01
NUMBER OF SEQ ID NOS: 87
SEQ ID NO 16
LENGTH: 107
TYPE: PRT
ORGANISM: Mus musculus
Query Match 100.0%; Score 555; Length 107;
Best Local Similarity 100.0%;
Matches 107; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQTTSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYYTSRLYSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQTTSSLSASLGDRVTISCRASQDISNYLNWYQQKPDGTVKLLIYYTSRLYSGVPS 60
Qy 61 RFSGSGSGTDYSLTISNLEPKDIATYYCQQFSELPRTFGGGTKLEIK 107
|||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDYSLTISNLEPKDIATYYCQQFSELPRTFGGGTKLEIK 107
Alignment of SEQ ID NO: 48 with SEQ ID NO: 19 of Heusser
Sequence 19, US/13295141
Publication No. US20120121585A1
GENERAL INFORMATION
APPLICANT: Novartis AG
TITLE OF INVENTION: Silent Fc variants of anti-CD40 antibodies
FILE REFERENCE: PAT54423
CURRENT APPLICATION NUMBER: US/13/295,141
CURRENT FILING DATE: 2012-01-31
PRIOR APPLICATION NUMBER: US 61/413567
PRIOR FILING DATE: 2010-11-15
NUMBER OF SEQ ID NOS: 28
SEQ ID NO 19
LENGTH: 217
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 100.0%; Score 1165; Length 217;
Best Local Similarity 100.0%;
Matches 217; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 APEAAGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK 60
Qy 61 PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PREEQYNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT 120
Qy 121 LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL 180
Qy 181 TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 217
|||||||||||||||||||||||||||||||||||||
Db 181 TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 217
Alignment of SEQ ID NO: 50 with SEQ ID NO: 17 of Heusser
RESULT 1
US-13-295-141-17
(NOTE: this sequence has 19 duplicates in the database searched.
See complete list at the end of this report)
Sequence 17, US/13295141
Publication No. US20120121585A1
GENERAL INFORMATION
APPLICANT: Novartis AG
TITLE OF INVENTION: Silent Fc variants of anti-CD40 antibodies
FILE REFERENCE: PAT54423
CURRENT APPLICATION NUMBER: US/13/295,141
CURRENT FILING DATE: 2012-01-31
PRIOR APPLICATION NUMBER: US 61/413567
PRIOR FILING DATE: 2010-11-15
NUMBER OF SEQ ID NOS: 28
SEQ ID NO 17
LENGTH: 217
TYPE: PRT
ORGANISM: Homo sapiens
Query Match 100.0%; Score 1163; Length 217;
Best Local Similarity 100.0%;
Matches 217; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 APELLGGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTK 60
Qy 61 PREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 PREEQYASTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYT 120
Qy 121 LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 LPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKL 180
Qy 181 TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 217
|||||||||||||||||||||||||||||||||||||
Db 181 TVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK