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 .
2. Applicant’s amendment filed on 07/08/2026 is acknowledged.
3. Claims 1-13 and 17 are pending.
4. Applicant’s election without traverse of Group I and the species of the subject having increased expression of IL-36ℽ in skin affected by hidradenitis suppurativa and the inhibitor of SEQ ID NOs 22 and 44 in the reply filed on 07/08/2026 is acknowledged.
5. Claims 1-13 and 17 are under consideration as they read on the inhibitor of SEQ ID Nos 22 and 44.
6. Applicant’s IDS documents filed on 10/05/2023 and 03/28/2025 have been considered.
7. 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.
8. Claims 1-13 and 17 rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-22 of U.S. Patent No. 10,526,410 (IDS filed on 10/05/2023; Reference 13) in view of Hessam et al. (PTO-892; Reference U).
U.S. Patent No. 10,526,410 teaches an interleukin-36 receptor (IL-36R) binding agent comprising an immunoglobulin heavy chain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 22, and an immunoglobulin light chain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 44, wherein the IL-36R binding agent is an antibody or antigen-binding antibody fragmentof claim 1; wherein the IL-36R binding agent is part of an antibody conjugate of claim 2; wherein the IL-36R binding agent is a F(ab′).sub.2, Fab′, Fab, Fv, scFv, dsFv, or a single chain binding polypeptide of claim 3; wherein the IL-36R binding agent is an IgG1 antibody of claim 4; wherein the IL-36R-binding agent binds to IL-36R with a K.sub.D between about 1 picomolar (pM) and about 200 pM when measured by surface plasmon resonance analysis of claim 5; a pharmaceutical composition comprising (a) the IL-36R-binding agent of claim 1, and (b) a pharmaceutically acceptable carrier of claim 6; an anti-interleukin-36 receptor (IL-36R) binding agent comprising the immunoglobulin heavy chain variable region of SEQ ID NO: 22, and the immunoglobulin light chain variable region of SEQ ID NO: 44, wherein the IL-36R binding agent is an antibody or antigen-binding antibody fragment of claim 7; wherein the IL-36R binding agent is part of an antibody conjugate of claim 8; wherein the IL-36R binding agent is a F(ab′).sub.2, Fab′, Fab, Fv, scFv, dsFv, or a single chain binding polypeptide of claim 9; wherein the IL-36R binding agent is an IgG1 antibody of claim 10; wherein the IL-36R-binding agent binds to IL-36R with a K.sub.D between about 1 picomolar (pM) and about 200 pM when measured by surface plasmon resonance analysis of claim 11; a pharmaceutical composition comprising (a) the IL-36R-binding agent of claim 7, and (b) a pharmaceutically acceptable carrier of claim 12; a method of treating a disorder in a mammal that is responsive to IL-36R inhibition, which method comprises administering an effective amount of the IL-6R binding agent of claim 1 to a mammal with a disorder that is responsive to IL-36R inhibition, whereupon the disorder is treated of claim 13; wherein the IL-36R binding agent is part of an antibody conjugate of claim 14; wherein the IL-36R binding agent is a F(ab′).sub.2, Fab′, Fab, Fv, scFv, dsFv, dAb, or a single chain binding polypeptide of claim 15; wherein the half-life of the IL-36R-binding agent in the mammal is between 30 minutes and 45 days of claim 16; wherein the IL-36R-binding agent binds to IL-36R with a K.sub.D between about 1 picomolar (pM) and about 200 pM when measured by surface plasmon resonance analysis of claim 17; a method of treating a disorder in a mammal that is responsive to IL-36R inhibition, which method comprises administering an effective amount of the IL-36R binding agent of claim 7 to a mammal with a disorder that is responsive to IL-36R inhibition, whereupon the disorder is treated of claim 18; wherein the IL-36R binding agent is part of an antibody conjugate of claim 19; wherein the IL-36R binding agent is a F(ab′).sub.2, Fab′, Fab, Fv, scFv, dsFv, dAb, or a single chain binding polypeptide of claim 20; wherein the half-life of the IL-36R-binding agent in the mammal is between 30 minutes and 45 days of claim 21; wherein the IL-36R-binding agent binds to IL-36R with a K.sub.D between about 1 picomolar (pM) and about 200 pM when measured by surface plasmon resonance analysis of claim 22.
Reference SEQ ID NO:s 22 and 44 are identical over length and sequence with instant SEQ ID NOs 22 and 44.
The claimed invention differs from the prior art in the recitation of a method of treating hidradenitits suppurtiva of claim 1; wherein the subject has increased expression of at least one of an interleukin-36 (IL-36) cytokine, interleukin-36 receptor (IL-36R), or mRNA encoding same in skin affected by the hidradenitis suppurativa of claim 4; and wherein the subject has increased expression of IL-36y in skin affected by the hidradenitis suppurativa of claim 5.
Hessam et al. teaches that IL-36α, IL-36β and IL-36γ were significantly overexpressed in inflamed lesional skin of patients with hidradenitis suppurativa, and there was a dysbalance between the agonistic and antagonistic cytokines in hidradenitis suppurativa skin (Fig. 3). The reference teaches the beneficial effects of targeting the IL-36 pathway on skin inflammation by blocking IL-36R and that an antibody against IL-36R has been developed for clinical use in patients with psoriasis. The reference further teaches the potential for targeting IL-36–IL-36R signaling in the therapy of hidradenitis suppurativa.(In particular, first paragraph of discussion and last paragraph, whole document).
It would have been obvious to one of ordinary skill in the art at the time of invention to have applied the method of treating a disorder in a mammal that is responsive to IL-36R inhibition comprising administering an effective amount of the IL-36R binding agent of SEQ ID NOs 22 and 44 to a mammal with a disorder that is responsive to IL-36R inhibition, whereupon the disorder is treated of US Patent 10,526,410 to treating hidradenitis suppurativa as taught by Hessam et al. because Hessam et al. teaches that IL-36α, IL-36β and IL-36γ were significantly overexpressed in inflamed lesional skin of patients with hidradenitis suppurativa and teaches that targeting IL-36–IL-36R signaling using an antibody, like has been done in the treatment of psoriasis, can be performed in the therapy of hidradenitis suppurativa.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
9. Claims 1-13 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-27 of U.S. Patent No. 11,130,814 (PTO-892; Reference A) in view of Hessam et al. (PTO-892; Reference U).
U.S. Patent No. 11,130,814 teaches a method of treating generalized pustular psoriasis (GPP) in a human patient comprising administering to the patient an interleukin-36 receptor (IL-36R) binding agent comprising an immunoglobulin heavy chain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 22, and an immunoglobulin light chain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 44 of claim 1; wherein the IL-36R binding agent comprises the immunoglobulin heavy chain variable region of SEQ ID NO: 22 of claim 2; wherein the IL-36R binding agent comprises the immunoglobulin light chain variable region of SEQ ID NO: 44 of claim 3; wherein the IL-36R binding agent comprises the immunoglobulin heavy chain variable region of SEQ ID NO: 22 and the immunoglobulin light chain variable region of SEQ ID NO: 44 of claim 4; wherein the IL-36R binding agent is a F(ab′).sub.2, Fab′, Fab, Fv, scFv, dsFv, or diabody of claim 5; wherein the IL-36R binding agent is an antibody of claim 6; wherein the IL-36R binding agent is an IgG1 antibody of claim 7; wherein the IL-36R binding agent is an IgG1 antibody of claim 8; wherein the IL-36R binding agent binds to IL-36R with a K.sub.D between about 1 picomolar (pM) and about 200 pM when measured by surface plasmon resonance analysis of claim 9; a method of treating palmoplantar pustulosis (PPP) in a human patient comprising administering to the patient an interleukin-36 receptor (IL-36R) binding agent comprising an immunoglobulin heavy chain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 22, and an immunoglobulin light chain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 44 of claim 10; wherein the IL-36R binding agent comprises the immunoglobulin heavy chain variable region of SEQ ID NO: 22 of claim 11; wherein the IL-36R binding agent comprises the immunoglobulin light chain variable region of SEQ ID NO: 44 of claim 12; wherein the IL-36R binding agent comprises the immunoglobulin heavy chain variable region of SEQ ID NO: 22 and the immunoglobulin light chain variable region of SEQ ID NO: 44 of claim 13; wherein the IL-36R binding agent is a F(ab′).sub.2, Fab′, Fab, Fv, scFv, dsFv, or diabody of claim 14; wherein the IL-36R binding agent is an antibody of claim 15; wherein the IL-36R binding agent is an IgG1 antibody of claim 16; wherein the IL-36R binding agent is an IgG1 antibody of claim 17; wherein the IL-36R binding agent binds to IL-36R with a K.sub.D between about 1 picomolar (pM) and about 200 pM when measured by surface plasmon resonance analysis of claim 18; a method of treating pustular psoriasis in a human patient comprising administering to the patient an effective amount of an interleukin-36 receptor (IL-36R) binding agent comprising an immunoglobulin heavy chain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 22, and an immunoglobulin light chain comprising CDR1, CDR2, and CDR3 of SEQ ID NO: 44 of claim 19; wherein the IL-36R binding agent comprises the immunoglobulin heavy chain variable region of SEQ ID NO: 22 of claim 20; wherein the IL-36R binding agent comprises the immunoglobulin light chain variable region of SEQ ID NO: 44 of claim 21; wherein the IL-36R binding agent comprises the immunoglobulin heavy chain variable region of SEQ ID NO: 22 and the immunoglobulin light chain variable region of SEQ ID NO: 44 of claim 22; wherein the IL-36R binding agent is a F(ab′).sub.2, Fab′, Fab, Fv, scFv, dsFv, or diabody of claim 23; wherein the IL-36R binding agent is an antibody of claim 24; wherein the IL-36R binding agent is an IgG1 antibody of claim 25; wherein the IL-36R binding agent is an IgG1 antibody of claim 26; and wherein the IL-36R binding agent binds to IL-36R with a K.sub.D between about 1 picomolar (pM) and about 200 pM when measured by surface plasmon resonance analysis of claim 27.
Reference SEQ ID NO:s 22 and 44 are identical over length and sequence with instant SEQ ID NOs 22 and 44.
The claimed invention differs from the prior art in the recitation of a method of treating hidradenitits suppurtiva of claim 1; wherein the subject has increased expression of at least one of an interleukin-36 (IL-36) cytokine, interleukin-36 receptor (IL-36R), or mRNA encoding same in skin affected by the hidradenitis suppurativa of claim 4; and wherein the subject has increased expression of IL-36y in skin affected by the hidradenitis suppurativa of claim 5.
Hessam et al. teaches that IL-36α, IL-36β and IL-36γ were significantly overexpressed in inflamed lesional skin of patients with hidradenitis suppurativa, and there was a dysbalance between the agonistic and antagonistic cytokines in hidradenitis suppurativa skin (Fig. 3). The reference teaches that in psoriasis, a disease characterized by chronic skin inflammation and several histological skin alterations similar to those in hidradenitis suppurativa, IL-36 expression (α, β and γ) has been reported to be enhanced in lesional human skin and in psoriasis mouse models. Furthermore, in IL-36R-deficient mice, psoriasiform dermatitis induced by imiquimod were completely inhibited, suggesting that IL-36 signalling is critical for the control of the IL-23–IL-17–IL-22 axis. Notably, overexpression of the IL-23–Th17 pathway is also seen in hidradenitis suppurativa. The reference teaches the beneficial effects of targeting the IL-36 pathway on skin inflammation by blocking IL-36R and that an antibody against IL-36R has been developed for clinical use in patients with psoriasis. The reference further teaches the potential for targeting IL-36–IL-36R signaling in the therapy of hidradenitis suppurativa.(In particular, first paragraph of discussion to the last paragraph, whole document).
It would have been obvious to one of ordinary skill in the art at the time of invention to have applied the method of treating generalized pustular psoriasis (GPP), palmoplantar pustulosis (PPP) and pustular psoriasis comprising administering an effective amount of the IL-36R binding agent of SEQ ID NOs 22 and 44 of US Patent 11,130,814 to treating hidradenitis suppurativa as taught by Hessam et al. because Hessam et al. teaches that IL-36α, IL-36β and IL-36γ were significantly overexpressed in inflamed lesional skin of patients with hidradenitis suppurativa and teaches that targeting IL-36–IL-36R signaling using an antibody, like has been effectively done in the treatment of psoriasis, can be performed in the therapy of hidradenitis suppurativa.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
10. Claims 1-13 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12,391,761 (PTO-892; Reference B) in view of Hessam et al. (PTO-892; Reference U).
U.S. Patent No. 12,391,761 teaches an isolated immunoglobulin light chain polypeptide which comprises the amino acid sequence of Gln Val Gln Xaa1 Xaa2 Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Thr Phe Thr Ser Tyr Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Xaa3 Leu Glu Trp Met Gly Trp Ile Tyr Pro Gly Asp Xaa4 Ser Thr Lys Tyr Asn Glu Lys Phe Lys Gly Arg Val Thr Ile Thr Xaa5 Asp Xaa6 Ser Ala Xaa7 Thr Ala Tyr Met Glu Leu Xaa8 Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Xaa9 Cys Thr Arg Ser Phe Tyr Thr Met Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser (SEQ ID NO: 56), wherein (a) Xaa1 is leucine (Leu) or phenylalanine (Phe), (b) Xaa2 is valine (Val), methionine (Met), or leucine (Leu), (c) Xaa3 is arginine (Arg) or glycine (Gly), (d) Xaa4 is glycine (Gly), serine (Ser), or alanine (Ala), (e) Xaa5 is arginine (Arg) or alanine (Ala), (f) Xaa6 is threonine (Thr) or lysine (Lys), (g) Xaa7 is serine (Ser) or asparagine (Asn), (h) Xaa8 is serine (Ser) or alanine (Ala), and (i) Xaa9 is tyrosine (Tyr) or phenylalanine (Phe); or an isolated immunoglobulin heavy chain polypeptide which comprises the amino acid sequence of Gln Val Gln Leu Val Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Xaa1 Met Xaa2 Trp Val Arg Gln Ala Pro Xaa3 Gln Gly Leu Glu Trp Met Gly Met Phe Xaa4 Pro Xaa5 Xaa6 Xaa7 Val Thr Arg Leu Asn Gln Lys Phe Lys Asp Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Thr Thr Ser Met Ile Ile Gly Gly Phe Ala Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser (SEQ ID NO: 15), wherein (a) Xaa1 is tryptophan (Trp) or tyrosine (Tyr), (b) Xaa2 is histidine (His), asparagine (Asn), or tyrosine (Tyr), (c) Xaa3 is glycine (Gly) or arginine (Arg), (d) Xaa4 is aspartic acid (Asp), glutamic acid (Glu), or histidine (His), (e) Xaa5 is serine (Ser), threonine (Thr), or tyrosine (Tyr), (f) Xaa6 is asparagine (Asn) or glycine (Gly), and (g) Xaa7 is serine (Ser), alanine (Ala), or aspartic acid (Asp); or an isolated immunoglobulin light chain polypeptide which comprises the amino acid sequence of Xaa1 Xaa2 Gln Xaa3 Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Xaa4 Xaa5 Tyr Ser Ile Thr Xaa6 Asp Phe Ala Trp Asn Trp Ile Arg Gln Xaa7 Pro Gly Xaa8 Xaa9 Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Asp Thr Asn Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Xaa10 Xaa11 Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Xaa12 Tyr Xaa13 Cys Ala Ile Arg Gly Pro Tyr Ser Phe Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser Xaa14 (SEQ ID NO: 57), wherein (a) Xaa1 is glutamine (Gln) or aspartic acid (Asp), (b) Xaa2 is valine (Val) or leucine (Leu), (c) Xaa3 is leucine (Leu) or phenylalanine (Phe), (d) Xaa4 is threonine (Thr) or serine (Ser), (e) Xaa5 is glycine (Gly) or arginine (Arg), (f) Xaa6 serine (Ser) or alanine (Ala), (g) Xaa7 is proline (Pro) or phenylalanine (Phe), (h) Xaa8 is lysine (Lys) or asparagine (Asn), (i) Xaa9 is glycine (Gly) or lysine (Lys), (j) Xaa10 is serine (Ser) or threonine (Thr), (k) Xaa11 is valine (Val) or arginine (Arg), (l) Xaa12 is threonine (Thr) or valine (Val), (m) Xaa13 is tyrosine (Tyr) or phenylalanine (Phe), and (n) Xaa14 is alanine (Ala) or absent or an isolated immunoglobulin light chain polypeptide which comprises the amino acid sequence of Asp Ile Val Met Thr Gln Thr Pro Leu Ser Leu Ser Val Thr Pro Gly Gln Pro Ala Ser Ile Ser Cys Arg Ser Ser Lys Ser Leu Leu His Xaa1 Asn Xaa2 Ile Thr Tyr Phe Tyr Trp Tyr Leu Xaa3 Lys Pro Gly Gln Pro Pro Gln Leu Leu Ile Tyr Gln Met Ser Asn Leu Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys Ile Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ala Gln Asn Leu Glu Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys (SEQ ID NO: 40), (a) Xaa1 is serine (Ser) or arginine (Arg), (b) Xaa2 is glycine (Gly) or alanine (Ala), and (c) Xaa3 is glutamine (Gln) or histidine (His); or an isolated immunoglobulin light chain polypeptide which comprises the amino acid sequence of Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Xaa1 Ile Asn Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Xaa2 Leu His Ser Gly Val Pro Ser Arg Phe Ser Xaa3 Ser Gly Ser Gly Xaa4 Asp Xaa5 Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly His Thr Leu Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys Xaa6 Xaa7 (SEQ ID NO: 58), wherein (a) Xaa1 is aspartic acid (Asp) or tryptophan (Trp), (b) Xaa2 is arginine (Arg) or methionine (Met), (c) Xaa3 is glycine (Gly), serine (Ser) or proline (Pro), (d) Xaa4 is threonine (Thr) or asparagines (Asn), (e) Xaa5 is phenylalanine (Phe) or tyrosine (Tyr), (f) Xaa6 is arginine (Arg) or absent, and (g) Xaa7 is threonine (Thr) or absent; or an isolated immunoglobulin heavy chain polypeptide which comprises the amino acid sequence of SEQ ID NO: 33, SEQ ID NO: 34, or SEQ ID NO: 35; or an isolated immunoglobulin light chain polypeptide which comprises the amino acid sequence of SEQ ID NO: 37, SEQ ID NO: 38, SEQ ID NO: 39, SEQ ID NO: 48, SEQ ID NO: 49, or SEQ ID NO: 50 of claim 1; an isolated immunoglobulin heavy chain polypeptide of claim 1, wherein the polypeptide comprises the amino acid sequence of Gln Val Gln Xaa1 Xaa2 Gln Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Thr Phe Thr Ser Tyr Asp Ile Asn Trp Val Arg Gln Ala Pro Gly Gln Xaa3 Leu Glu Trp Met Gly Trp Ile Tyr Pro Gly Asp Xaa4 Ser Thr Lys Tyr Asn Glu Lys Phe Lys Gly Arg Val Thr Ile Thr Xaa5 Asp Xaa6 Ser Ala Ser Thr Ala Tyr Met Glu Leu Xaa7 Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Xaa8 Cys Thr Arg Ser Phe Tyr Thr Met Asp Tyr Trp Gly Gln Gly Thr Thr Val Thr Val Ser Ser (SEQ ID NO: 1), wherein (a) Xaa1 is leucine (Leu) or phenylalanine (Phe), (b) Xaa2 is valine (Val), methionine (Met), or leucine (Leu), (c) Xaa3 is arginine (Arg) or glycine (Gly), (d) Xaa4 is glycine (Gly), serine (Ser), or alanine (Ala), (e) Xaa5 is arginine (Arg) or alanine (Ala), (f) Xaa6 is threonine (Thr) or lysine (Lys), (g) Xaa7 is serine (Ser) or alanine (Ala), and (h) Xaa8 is tyrosine (Tyr) or phenylalanine (Phe); or an isolated immunoglobulin heavy chain polypeptide of claim 1, wherein the polypeptide comprises the amino acid sequence of Xaa1 Val Gln Xaa2 Gln Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gln Thr Leu Ser Leu Thr Cys Thr Val Xaa3 Gly Tyr Ser Ile Thr Ser Asp Phe Ala Trp Asn Trp Ile Arg Gln Xaa4 Pro Gly Xaa5 Xaa6 Leu Glu Trp Ile Gly Tyr Ile Ser Tyr Ser Gly Asp Thr Asn Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr Ile Xaa7 Xaa8 Asp Thr Ser Lys Asn Gln Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Xaa9 Cys Ala Ile Arg Gly Pro Tyr Ser Phe Thr Tyr Trp Gly Gln Gly Thr Leu Val Thr Val Ser Ser (SEQ ID NO: 25), wherein (a) Xaa1 is glutamine (Gln) or aspartic acid (Asp), (b) Xaa2 is leucine (Leu) or phenylalanine (Phe), Xaa3 is threonine (Thr) or serine (Ser), (c) Xaa4 is proline (Pro) or phenylalanine (Phe), (d) (e) Xaa5 is lysine (Lys) or asparagine (Asn), (f) Xaa6 is glycine (Gly) or lysine (Lys), (g) Xaa7 is serine (Ser) or threonine (Thr), (h) Xaa8 is valine (Val) or arginine (Arg), and (i) Xaa9 is tyrosine (Tyr) or phenylalanine (Phe) of claim 2; an isolated immunoglobulin heavy chain polypeptide of claim 1, which comprises the amino acid sequence of any one of SEQ ID NOs: 2-14, 16-24, 26-32, or 51-54 of claim 3; an isolated immunoglobulin light chain polypeptide of claim 1, wherein the polypeptide comprises the amino acid sequence of Asp Ile Gln Met Thr Gln Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr Ile Thr Cys Arg Ala Ser Gln Asp Ile Asn Asn Tyr Leu Asn Trp Tyr Gln Gln Lys Pro Gly Lys Ala Pro Lys Leu Leu Ile Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Xaa1 Ser Gly Ser Gly Thr Asp Xaa2 Thr Phe Thr Ile Ser Ser Leu Gln Pro Glu Asp Ile Ala Thr Tyr Tyr Cys Gln Gln Gly His Thr Leu Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu Ile Lys (SEQ ID NO: 45), wherein (a) Xaa1 is serine (Ser) or proline (Pro), and (b) Xaa2 is phenylalanine (Phe) or tyrosine (Tyr) of claim 4; an isolated immunoglobulin light chain polypeptide of claim 1, which comprises the amino acid sequence of any one of SEQ ID NOs: 37-39, 41-44, 46, 47, or 55 of claim 5; an interleukin 36 receptor (IL-36R)-binding agent comprising an immunoglobulin heavy chain polypeptide and an immunoglobulin light chain polypeptide of claim 1, or comprising an immunoglobulin heavy chain of claim 1 and an immunoglobulin light chain of SEQ ID NO: 36 of claim 6; which is an antibody, an antibody conjugate, or an antigen-binding fragment thereof of claim 7; which is a F (ab′) 2 fragment, a Fab′ fragment, a Fab fragment, a Fv fragment, a scFv fragment, a dsFv fragment, a dAb fragment, or a diabody of claim 8; a composition comprising (a) the IL-36R-binding agent of claim 6 and (b) a pharmaceutically acceptable carrier of claim 9; an interleukin 36 receptor (IL-36R)-binding agent comprising: an immunoglobulin heavy chain polypeptide which comprises the amino acid sequence of SEQ ID NO: 22 and an immunoglobulin light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 43, an immunoglobulin heavy chain polypeptide which comprises the amino acid sequence of SEQ ID NO: 22 and an immunoglobulin light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 44, or an immunoglobulin heavy chain polypeptide which comprises the amino acid sequence of SEQ ID NO: 24 and an immunoglobulin light chain polypeptide comprising the amino acid sequence of SEQ ID NO: 44 of claim 10; a composition comprising (a) the IL-36R-binding agent of claim 10 and (b) a pharmaceutically acceptable carrier of claim 11; a method of treating generalized pustular psoriasis (GPP), palmo-plantar pustulosis (PPP), or pustular psoriasis in a mammal in need thereof, said method comprising administering an effective amount of the composition of claim 11 to the mammal, whereupon the GPP, PPP or pustular psoriasis is treated of claim 12; wherein the half-life of the IL-36R-binding agent in the mammal is between 30 minutes and 45 days of claim 13; and wherein the IL-36R-binding agent binds to IL-36R with a KD between about 1 picomolar (pM) and about 100 micromolar (μM) of claim 14.
Reference SEQ ID NO:s 22 and 44 are identical over length and sequence with instant SEQ ID NOs 22 and 44.
The claimed invention differs from the prior art in the recitation of a method of treating hidradenitits suppurtiva of claim 1; wherein the subject has increased expression of at least one of an interleukin-36 (IL-36) cytokine, interleukin-36 receptor (IL-36R), or mRNA encoding same in skin affected by the hidradenitis suppurativa of claim 4; and wherein the subject has increased expression of IL-36y in skin affected by the hidradenitis suppurativa of claim 5.
Hessam et al. teaches that IL-36α, IL-36β and IL-36γ were significantly overexpressed in inflamed lesional skin of patients with hidradenitis suppurativa, and there was a dysbalance between the agonistic and antagonistic cytokines in hidradenitis suppurativa skin (Fig. 3). The reference teaches that in psoriasis, a disease characterized by chronic skin inflammation and several histological skin alterations similar to those in hidradenitis suppurativa, IL-36 expression (α, β and γ) has been reported to be enhanced in lesional human skin and in psoriasis mouse models. Furthermore, in IL-36R-deficient mice, psoriasiform dermatitis induced by imiquimod were completely inhibited, suggesting that IL-36 signalling is critical for the control of the IL-23–IL-17–IL-22 axis. Notably, overexpression of the IL-23–Th17 pathway is also seen in hidradenitis suppurativa. The reference teaches the beneficial effects of targeting the IL-36 pathway on skin inflammation by blocking IL-36R and that an antibody against IL-36R has been developed for clinical use in patients with psoriasis. The reference further teaches the potential for targeting IL-36–IL-36R signaling in the therapy of hidradenitis suppurativa.(In particular, first paragraph of discussion to the last paragraph, whole document).
It would have been obvious to one of ordinary skill in the art at the time of invention to have applied the method of treating generalized pustular psoriasis (GPP), palmoplantar pustulosis (PPP) and pustular psoriasis comprising administering an effective amount of the IL-36R binding agent of SEQ ID NOs 22 and 44 of US Patent 12,391,761 to treating hidradenitis suppurativa as taught by Hessam et al. because Hessam et al. teaches that IL-36α, IL-36β and IL-36γ were significantly overexpressed in inflamed lesional skin of patients with hidradenitis suppurativa and teaches that targeting IL-36–IL-36R signaling using an antibody, like has been effectively done in the treatment of psoriasis, can be performed in the therapy of hidradenitis suppurativa.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
11. Claims 1-13 and 17 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 12,715,924 (PTO-892; Reference C) in view of Hessam (PTO-892; Reference U).
U.S. Patent No. 12,715,924 teaches a method of treating ichthyosis in a subject, the method comprising administering to the subject an IL 36R-binding agent that comprises a heavy chain comprising: a HCDR1 of SEQ ID NO: 65, a HCDR2 of SEQ ID NO: 71, and HCDR3 of SEQ ID No: 72; and a light chain polypeptide comprising: or at least a LCDR1 of SEQ ID NO: 83, LCDR2 of SEQ ID NO: 84, and LCDR3 of SEQ ID NO: 85 of claim 1; wherein the ichthyosis is congenital ichthyosiform erythroderma, lamellar ichthyosis, epidermolytic ichthyosis, Netherton syndrome, or ichthyosis with confetti of claim 2; wherein the subject is a mammal of claim 3; wherein the mammal is a human of claim 4; wherein the subject has increased skin expression of at least one of an interleukin 36 (IL-36) cytokine, interleukin-36 receptor (IL-36R), or mRNA encoding same of claim 5; wherein the IL-36 cytokine is IL-36α, IL-36β, or IL-36γ of claim 6; wherein the immunoglobulin heavy chain polypeptide of the IL-36R-binding agent comprises SEQ ID NO: 22 or at least the CDRs thereof of claim 7; wherein the immunoglobulin light chain polypeptide of the IL-36-binding agent comprises SEQ ID NO: 44 or at least the CDRs thereof of claim 8; wherein the IL-36R-binding agent exhibits one or more of the following biological activities: (a) inhibits the interaction between IL-36R and IL-36α, IL-36β, and/or IL-36γ, (b) inhibits intracellular signaling mediated by IL-36R, (c) cross-reacts with and inhibits the activity of human IL-36R, cynomolgus IL-36R, and non-human primate IL-36R of claim 9; wherein the IL-36R-binding agent is an antibody, an antibody conjugate, or an antigen-binding fragment thereof of claim 10; wherein the IL-36R-binding agent is a F(ab′).sub.2 fragment, a Fab′ fragment, a Fab fragment, a Fv fragment, a scFv fragment, a dsFv fragment, a dAb fragment, or a single-chain binding polypeptide of claim 11; wherein the method comprises administering the IL-36R-binding agent with a pharmaceutically acceptable carrier of claim 12; wherein the half-life of the IL-36R-binding agent in the mammal after administration is between 30 minutes and 45 days of claim 13; and wherein the IL-36R-binding agent binds to IL-36R with a KD between about 1 picomolar (pM) and about 100 micromolar (μM) of claim 14.
Reference SEQ ID NO:s 22 and 44 are identical over length and sequence with instant SEQ ID NOs 22 and 44.
The claimed invention differs from the prior art in the recitation of a method of treating hidradenitits suppurtiva of claim 1.
Hessam et al. teaches that IL-36α, IL-36β and IL-36γ were significantly overexpressed in inflamed lesional skin of patients with hidradenitis suppurativa, and there was a dysbalance between the agonistic and antagonistic cytokines in hidradenitis suppurativa skin (Fig. 3). The reference teaches that in psoriasis, a disease characterized by chronic skin inflammation and several histological skin alterations similar to those in hidradenitis suppurativa, IL-36 expression (α, β and γ) has been reported to be enhanced in lesional human skin and in psoriasis mouse models. Furthermore, in IL-36R-deficient mice, psoriasiform dermatitis induced by imiquimod were completely inhibited, suggesting that IL-36 signalling is critical for the control of the IL-23–IL-17–IL-22 axis. Notably, overexpression of the IL-23–Th17 pathway is also seen in hidradenitis suppurativa. The reference teaches the beneficial effects of targeting the IL-36 pathway on skin inflammation by blocking IL-36R and that an antibody against IL-36R has been developed for clinical use in patients with psoriasis. The reference further teaches the potential for targeting IL-36–IL-36R signaling in the therapy of hidradenitis suppurativa.(In particular, first paragraph of discussion to the last paragraph, whole document).
It would have been obvious to one of ordinary skill in the art at the time of invention to have applied the method of treating ichthyosis comprising administering an effective amount of the IL-36R binding agent of SEQ ID NOs 22 and 44 of US Patent 12,715,924 to treating hidradenitis suppurativa as taught by Hessam et al. because Hessam et al. teaches that IL-36α, IL-36β and IL-36γ were significantly overexpressed in inflamed lesional skin of patients with hidradenitis suppurativa and teaches that targeting IL-36–IL-36R signaling using an antibody, like has been effectively done in the treatment of psoriasis, can be performed in the therapy of hidradenitis suppurativa. Since ichthyosis is a disease characterized by an increased skin expression of at least one of an interleukin 36 (IL-36) cytokine, interleukin-36 receptor (IL-36R), or mRNA encoding wherein the IL-36 cytokine is IL-36α, IL-36β, or IL-36γ and can be treated with the antibody of reference SeqID NOs 24 and 44 it would be obvious to treat hidradenitis suppurativa since Hessam et al. teaches that IL-36α, IL-36β and IL-36γ were significantly overexpressed in inflamed lesional skin of patients with hidradenitis suppurativa, and there was a dysbalance between the agonistic and antagonistic cytokines in hidradenitis suppurativa skin. An antibody with the same target would be obvious to use for both ichthyosis and hidradenitis suppurativa.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
12. 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.
13. Claims 1-5 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being incomplete for omitting essential steps, such omission amounting to a gap between the steps. See MPEP § 2172.01. The omitted step is a contact step. Claims 1-5 do not recite the administration of any reagents to the subject which would result in treatment.
Correction is required.
14. Claims 7-11 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 applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claims 7-11 refer to the CDRs of the IL-36R antibody, but they don’t refer to any particular numbering scheme or residue numbers. This makes the claim unclear, because it is not clear how the CDRs are defined. In fact, at paragraph [0020] the specification discloses that there are differing numbering schemes for CDRs.
The CDRs of a given Ig sequence can be determined by any of several conventional numbering schemes, such as Kabat, Chothia, Martin (Enhanced Chothia), IGMT, or AHo (see, e.g., Kabat, et al., Sequences ofProteins oflmmunological Interest, U.S. Department of Health and Human Services, NIH (1991); Chothia, et al., Canonical Structures for the Hypervariable Regions of Immunoglobulins, J. Mol. Biol., 196:901-917 (1987); Al-Lazikani et al., Standard Conformations for the Canonical Structures oflmmunoglobulins, J. Mol. Biol., 273:927 - 948 (1997), Abhinandan et al., Analysis and Improvements to Kabat and Structurally Correct Numbering ofAntibody Variable Domains, Mol. Immunol., 45: 3832 - 3839 (2008); Lefranc et al., The IMGT unique numbering for immunoglobulins, T cell Receptors and Ig-like domains, The Immunologist, 7: 132-136 (1999); Lefranc et al., IMGT unique numbering for immunoglobulin and T cell receptor variable domains and I superfamily V-like domains, Dev. Comp. Immunol., 27: 55 - 77 (2003); and Honegger et al., Yet another numbering scheme for immunoglobulin variable domains: an automatic modeling and analysis tool, J. Mol. Biol. 309: 657 - 670 (2001).
If one considers the CDRs to be defined by Chothia, then residues 26-32 are the minimal required region for LCDR1, for example. However, if one uses the CDRs as defined by Kabat, then LCDR1 is residues 24-34. This makes it unclear whether an antibody which includes residues 26-32 but differs at positions 24-25 and 33-34 is within the scope of the claim or not.
Correction is required.
15. 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.
Written Description
16. Claims 1-13 and 17 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 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.
Applicant is in possession of: a method of treating hidradenitis suppurativa comprising administering anti-IL-36R antibodies comprising all 6 CDRs.
Applicant is not in possession of: a method of treating hidradenitis suppurativa comprising administering “an IL-36R binding agent” or “an IL-36R binding antibody” or anti-IL-36R antibodies comprising less than all 6 CDRs.
Consequently, conception cannot be achieved until a representative description of the structural and functional properties of the claimed invention has occurred, regardless of the complexity or simplicity of the method.
The specification must set forth the structural features that allow one of ordinary skill in the art to identify and produce the recited antibodies. In the instant case, definition by function does not suffice to define the genus because it is only an indication of what the antibodies do, rather than what they are.
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function.
It was well known to those skilled in the art at the time the invention was made that minor structural differences among structurally related antibodies or compositions thereof could result in substantially different binding activities. Given the lack of guidance in the specification, it is unpredictable which antibodies with which structures would exhibit the recited functions. The specification does not describe a correlation between the structure of the IL-36R binding agent or antibodies themselves and their function of binding IL-36R such that a skilled artisan would have known what agent and antibody structures possess the claimed functions of bindingIL-36R.
"Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features" Ex parte Kubin (83 U.S.P.Q.2d 1410 (BPAI 2007)), at page 16. In this instant case, Applicants have not provided the requisite identifying structural features of the agents and antibodies encompassed. "Without a correlation between structure and function, the claim does little more than define the claimed invention by function" supra, at page 17.
U.S. Court of Appeals for the Federal Circuit recently decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017) which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § l 12(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen" test, which had been based on an example in USPTO- issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. § l 12(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co. , the court also stressed that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional. Id.
The specification does not provide adequate written description of the claimed invention. The legal standard for sufficiency of a patent's (or a specification's) written description is whether that description "reasonably conveys to the artisan that the inventor had possession at that time of the ... claimed subject matter", Vas-Cath, Inc. V. Mahurkar, 19 U.S.P.Q.2d 1111 (Fed. Cir. 1991). In the instant case, the specification does not convey to the artisan that the applicant had possession at the time of invention of the claimed invention. regarding description of the claimed invention, the specification does not provide an adequate written description of the invention claimed herein. See The Regents of the University of California v. Eli Lilly and Company, 43 USPQ2d 1398, 1404-7 (Fed. Cir. 1997). In University of California v. Eli Lilly and Co., 39 U.S.P.Q.2d 1225 (Fed. Cir. 1995) the inventors claimed a genus of DNA species encoding insulin in different vertebrates or mammals, but had only described a single species of cDNA which encoded rat insulin. The court held that only the nucleic acids species described
in the specification (i.e. nucleic acids encoding rat insulin) met the description
requirement and that the inventors were not entitled to a claim encompassing a genus
of nucleic acids encoding insulin from other vertebrates, mammals or humans, id. at
1240. The Federal Circuit has held that if an inventor is "unable to envision the detailed
constitution of a gene so as to distinguish it from other materials . . . conception has not
been achieved until reduction to practice has occurred", Amgen, Inc. v. Chugai
Pharmaceutical Co, Ltd., 18 U.S.P.Q.2d 016 (Fed. Cir. 1991). Attention is also directed
to the decision of The Regents of the University of California v. Eli Lilly and Company
(CAFC, July 1997) wherein is stated: "The description requirement of the patent statute
requires a description of an invention, not an indication of a result that one might
achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 222 USPQ 369,
372-373 (Fed. Cir. 1984) (affirming rejection because the specification does "little more
than outlin[ e] goals appellants hope the claimed invention achieves and the problems
the invention will hopefully ameliorate."). Accordingly, naming a type of material
generally known to exist, in the absence of knowledge as to what that material consists
of, is not a description of that material. Thus, as we have previously held, a cDNA is not
defined or described by the mere name "cDNA," even if accompanied by the name of
the protein that it encodes, but requires a kind of specificity usually achieved by means of the recitation of the sequence of nucleotides that make up the cDNA." See Fiers, 984
F.2d at 1171, 25 USPQ2d at 1606.
The Guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112(a) or U.S.C 112, I 1 "Written Description" Requirement make clear that the written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice, reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical
and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus.
The claims are not supported by a description that satisfies 35 U.S.C. § 112(a) or 35 U.S.C. § 112, first paragraph. "[T]he test for sufficiency [of the written description] is whether the disclosure of the application relied upon reasonably conveys to those skilled in the art that the inventor had possession of the claimed subject matter as of the filing date." Ariad Phanns., Inc. V. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en bane).
A "sufficient description of a genus requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can 'visualize or recognize' the members of the genus." Id. at 1350. "[A]n adequate written description requires a precise definition, such as by structure, formula, chemical name, physical properties, or other properties, of species falling within the genus sufficient to distinguish the genus from other materials." Id.
"[F]unctional claim language can meet the written description requirement when the art has established a correlation between structure and function." Id. "But merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing that one has invented a genus and not just a species." Id.
"A sufficient description of a genus requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
With respect to representative number of species, see AbbVic Deutschland GmbH & Co.V. Janssen Biotech, Inc. (Fed. Cir. 2014). Also, see MPEP 2163 II(A)(3)(a))(ii):
"A representative number of species means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus. See Abb Vie Deutschland GmbH & Co., KG V. Janssen Biotech, Inc., 759 F.3d 1285, 1300, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (Claims directed to a functionally defined genus of antibodies were not supported by a disclosure that "only describe[d] one type of structurally similar antibodies" that "are not representative of the full variety or scope of the genus.")."
Satisfactory disclosure of a "representative number" depends on whether one of skill in the art would recognize that the applicant was in possession of the necessary common attributes or features possessed by the members of the genus in view of the species disclosed. For inventions in an unpredictable art, adequate written description of a genus which embraces widely variant species cannot be achieved by disclosing only one species within the genus. See, e.g., Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406. Instead, the disclosure must adequately reflect the structural diversity of the claimed genus, either through the disclosure of sufficient species that are "representative of the full variety or scope of the genus," or by the establishment of "a reasonable structure-function correlation." Such correlations may be established "by the inventor as described in the specification," or they may be "known in the art at the time of the filing date." See AbbVie, 759 F.3d at 1300-01, 111 USPQ2d 1780, 1790-91 (Fed. Cir. 2014) (Holding that claims to all human antibodies that bind IL-12 with a particular binding affinity rate constant (i.e., Koff) were not adequately supported by a specification describing only a single type of human antibody having the claimed features because the disclosed antibody was not representative of other types of antibodies in the claimed genus, as demonstrated by the fact that other disclosed antibodies had different types of heavy and light chains, and shared only a 50% sequence similarity in their variable regions with the disclosed antibodies.).
In the instant case, the antibodies disclosed in the specification do not sufficiently represent the broad genus of binding agents and antibodies which bind IL-36 and inhibit IL-36 signaling.
Given the broadly claimed class of structures with the function of bind IL-36 and inhibit IL-36 signaling and in the absence of sufficient disclosure of relevant identifying characteristics for the broadly claimed class of binding agents and antibodies encompassed by the claims, the patentee must establish "a reasonable structure-function correlation" either within the specification or by reference to the knowledge of one skilled in the art with functional claims. AbbVie Deutschland GmbH & Co. V. Janssen Biotech, Inc. (Fed. Cir. 2014), MPEP 2163.
As such, there is insufficient written description of the required kind of structure
identifying information about the corresponding makeup of the claimed binding agents and antibodies to demonstrate possession.
17. In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
18. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
19. Claims 1-6, 12-13 and 17 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by WO 2020/132220 (IDS filed on 10/05/2023; Reference 42).
WO 2020/132220 teaches in paragraph [0208] the compositions or formulations comprising an anti-IL-36 antibody of the present disclosure can be used in a method, therapy, medicament, diagnostic, or use for use in the treatment of hidradenitis suppurativa and in claims 65-66 a method of treating a disease mediated by IL-36α, IL-36β, and/or IL-36γ stimulated signaling in a subject, the method comprising administering to the subject a therapeutically effective amount of an anti-IL-36 antibody or a therapeutically effective amount of a pharmaceutical composition wherein the disease is hidradenitis suppurativa.
The reference teachings anticipate the claimed invention.
20. 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.
21. Claims 1-13 and 17 are rejected under 35 U.S.C. 103 as being unpatentable over WO 2016/168542 (IDS filed on 10/05/0223; Reference 41) in view of Hessam et al. (PTO-892; Reference U).
WO 2016/168542 teaches in the claims:
1. An isolated immunoglobulin light chain polypeptide which comprises the amino acid sequence of Gin Val Gin Xaal Xaa2 Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Thr Phe Thr Ser Tyr Asp He Asn Trp Val Arg Gin Ala Pro Gly Gin Xaa3 Leu Glu Trp Met Gly Trp He Tyr Pro Gly Asp Xaa4 Ser Thr Lys Tyr Asn Glu Lys Phe Lys Gly Arg Val Thr He Thr Xaa5 Asp Xaa6 Ser Ala Xaa7 Thr Ala Tyr Met Glu Leu Xaa8 Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Xaa9 Cys Thr Arg Ser Phe Tyr Thr Met Asp Tyr Trp Gly Gin Gly Thr Thr Val Thr Val Ser Ser (SEQ ID NO: 56), wherein
(a) Xaal is leucine (Leu) or phenylalanine (Phe),
(b) Xaa2 is valine (Val), methionine (Met), or leucine (Leu),
(c) Xaa3 is arginine (Arg) or glycine (Gly),
(d) Xaa4 is glycine (Gly), serine (Ser), or alanine (Ala),
(e) Xaa5 is arginine (Arg) or alanine (Ala),
(f) Xaa6 is threonine (Thr) or lysine (Lys),
(g) Xaa7 is serine (Ser) or asparagine (Asn),
(h) Xaa8 is serine (Ser) or alanine (Ala), and
(i) Xaa9 is tyrosine (Tyr) or phenylalanine (Phe).
2. The isolated immunoglobulin heavy chain polypeptide of claim 1, wherein the polypeptide comprises the amino acid sequence of Gin Val Gin Xaal Xaa2 Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Phe Thr Phe Thr Ser Tyr Asp He Asn Trp Val Arg Gin Ala Pro Gly Gin Xaa3 Leu Glu Trp Met Gly Trp He Tyr Pro Gly Asp Xaa4 Ser Thr Lys Tyr Asn Glu Lys Phe Lys Gly Arg Val Thr He Thr Xaa5 Asp Xaa6 Ser Ala Ser Thr Ala Tyr Met Glu Leu Xaa7 Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Xaa8 Cys Thr Arg Ser Phe Tyr Thr Met Asp Tyr Trp Gly Gin Gly Thr Thr Val Thr Val Ser Ser (SEQ ID NO: 1), wherein
(a) Xaal is leucine (Leu) or phenylalanine (Phe),
(b) Xaa2 is valine (Val), methionine (Met), or leucine (Leu),
(c) Xaa3 is arginine (Arg) or glycine (Gly),
(d) Xaa4 is glycine (Gly), serine (Ser), or alanine (Ala),
(e) Xaa5 is arginine (Arg) or alanine (Ala),
(f) Xaa6 is threonine (Thr) or lysine (Lys),
(g) Xaa7 is serine (Ser) or alanine (Ala), and
(h) Xaa8 is tyrosine (Tyr) or phenylalanine (Phe).
3. The isolated immunoglobulin heavy chain polypeptide of claim 1, which comprises the amino acid sequence of any one of SEQ ID NO: 2, SEQ ID NO: 3, SEQ ID NO: 4, SEQ ID NO: 5, SEQ ID NO: 6, SEQ ID NO: 7, SEQ ID NO: 8, SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 13, or SEQ ID NO: 14.
4. An isolated immunoglobulin heavy chain polypeptide which comprises the amino acid sequence of Gin Val Gin Leu Val Gin Ser Gly Ala Glu Val Lys Lys Pro Gly Ala Ser Val Lys Val Ser Cys Lys Ala Ser Gly Tyr Thr Phe Thr Asn Tyr Xaal Met Xaa2 Trp Val Arg Gin Ala Pro Xaa3 Gin Gly Leu Glu Trp Met Gly Met Phe Xaa4 Pro Xaa5 Xaa6 Xaa7 Val Thr Arg Leu Asn Gin Lys Phe Lys Asp Arg Val Thr Met Thr Arg Asp Thr Ser Thr Ser Thr Val Tyr Met Glu Leu Ser Ser Leu Arg Ser Glu Asp Thr Ala Val Tyr Tyr Cys Ala Arg Thr Thr Ser Met He He Gly Gly Phe Ala Tyr Trp Gly Gin Gly Thr Leu Val Thr Val Ser Ser (SEQ ID NO: 15), wherein
(a) Xaal is tryptophan (Trp) or tyrosine (Tyr),
(b) Xaa2 is histidine (His), asparagine (Asn), or tyrosine (Tyr),
(c) Xaa3 is glycine (Gly) or arginine (Arg),
(d) Xaa4 is aspartic acid (Asp), glutamic acid (Glu), or histidine (His),
(e) Xaa5 is serine (Ser), threonine (Thr), or tyrosine (Tyr),
(f) Xaa6 is asparagine (Asn) or glycine (Gly), and
(g) Xaa7 is serine (Ser), alanine (Ala), or aspartic acid (Asp).
5. The isolated immunoglobulin heavy chain polypeptide of claim 4, which comprises the amino acid sequence of any one of SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19, SEQ ID NO: 20, SEQ ID NO: 21, SEQ ID NO: 22, SEQ ID NO: 23, or SEQ ID NO: 24.
6. An isolated immunoglobulin light chain polypeptide which comprises the amino acid sequence of Xaal Xaa2 Gin Xaa3 Gin Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gin Thr Leu Ser Leu Thr Cys Thr Val Xaa4 Xaa5 Tyr Ser He Thr Xaa6 Asp Phe Ala Trp Asn Trp He Arg Gin Xaa7 Pro Gly Xaa8 Xaa9 Leu Glu Trp He Gly Tyr He Ser Tyr Ser Gly Asp Thr Asn Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr He XaalO Xaal 1 Asp Thr Ser Lys Asn Gin Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Xaal2 Tyr Xaal3 Cys Ala He Arg Gly Pro Tyr Ser Phe Thr Tyr Trp Gly Gin Gly Thr Leu Val Thr Val Ser Ser Xaal4 (SEQ ID NO: 57), wherein
(a) Xaal is glutamine (Gin) or aspartic acid (Asp),
(b) Xaa2 is valine (Val) or leucine (Leu),
(c) Xaa3 is leucine (Leu) or phenylalanine (Phe),
(d) Xaa4 is threonine (Thr) or serine (Ser),
(e) Xaa5 is glycine (Gly) or arginine (Arg),
(f) Xaa6 serine (Ser) or alanine (Ala),
(g) Xaa7 is proline (Pro) or phenylalanine (Phe),
(h) Xaa8 is lysine (Lys) or asparagine (Asn),
(i) Xaa9 is glycine (Gly) or lysine (Lys),
(j) XaalO is serine (Ser) or threonine (Thr),
(k) Xaal 1 is valine (Val) or arginine (Arg),
(1) Xaal 2 is threonine (Thr) or valine (Val),
(m) Xaal 3 is tyrosine (Tyr) or phenylalanine (Phe), and
(n) Xaal 4 is alanine (Ala) or absent.
7. The isolated immunoglobulin heavy chain polypeptide of claim 1, wherein the polypeptide comprises the amino acid sequence of Xaal Val Gin Xaa2 Gin Glu Ser Gly Pro Gly Leu Val Lys Pro Ser Gin Thr Leu Ser Leu Thr Cys Thr Val Xaa3 Gly Tyr Ser lie Thr Ser Asp Phe Ala Trp Asn Trp He Arg Gin Xaa4 Pro Gly Xaa5 Xaa6 Leu Glu Trp He Gly Tyr He Ser Tyr Ser Gly Asp Thr Asn Tyr Asn Pro Ser Leu Lys Ser Arg Val Thr He Xaa7 Xaa8 Asp Thr Ser Lys Asn Gin Phe Ser Leu Lys Leu Ser Ser Val Thr Ala Ala Asp Thr Ala Val Tyr Xaa9 Cys Ala He Arg Gly Pro Tyr Ser Phe Thr Tyr Trp Gly Gin Gly Thr Leu Val Thr Val Ser Ser (SEQ ID NO: 25), wherein
(a) Xaal is glutamine (Gin) or aspartic acid (Asp),
(b) Xaa2 is leucine (Leu) or phenylalanine (Phe),
(c) Xaa3 is threonine (Thr) or serine (Ser),
(d) Xaa4 is proline (Pro) or phenylalanine (Phe),
(e) Xaa5 is lysine (Lys) or asparagine (Asn),
(f) Xaa6 is glycine (Gly) or lysine (Lys),
(g) Xaa7 is serine (Ser) or threonine (Thr),
(h) Xaa8 is valine (Val) or arginine (Arg), and
(i) Xaa9 is tyrosine (Tyr) or phenylalanine (Phe).
8. The isolated immunoglobulin heavy chain polypeptide of claim 6, which comprises the amino acid sequence of any one of SEQ ID NO: 26, SEQ ID NO: 27, SEQ ID NO: 28, SEQ ID NO: 29, SEQ ID NO: 30, SEQ ID NO: 31, SEQ ID NO: 32, SEQ ID NO: 51, SEQ ID NO: 52, SEQ ID NO: 53, or SEQ ID NO: 54.
9. An isolated immunoglobulin heavy chain polypeptide which comprises the amino acid sequence of SEQ ID NO: 33, SEQ ID NO: 34, or SEQ ID NO: 35.
10. An isolated immunoglobulin light chain polypeptide which comprises the amino acid sequence of Asp He Val Met Thr Gin Ser Pro Leu Ser Leu Pro Val Thr Pro Gly Glu Pro Ala Ser He Ser Cys Arg Ser Ser Lys Ser Leu Leu His Ser Asn Xaal Asn Thr Tyr Leu Tyr Trp Xaa2 Leu Gin Lys Pro Gly Gin Ser Pro Gin Leu Leu He Xaa3 Arg Met Ser Asn Leu Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys He Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Met Gin His Leu Glu Tyr Pro Phe Thr Phe Gly Gin Gly Thr Lys Leu Glu He Lys (SEQ ID NO: 36), wherein
(a) Xaal is glycine (Gly) or alanine (Ala),
(b) Xaa2 is phenylalanine (Phe) or tyrosine (Tyr), and
(c) Xaa3 is tyrosine (Tyr) or serine (Ser).
11. The isolated immunoglobulin light chain polypeptide of claim 10, which comprises the amino acid sequence of SEQ ID NO: 37, SEQ ID NO: 38, or SEQ ID NO: 39.
12. An isolated immunoglobulin light chain polypeptide which comprises the amino acid sequence of Asp He Val Met Thr Gin Thr Pro Leu Ser Leu Ser Val Thr Pro Gly Gin Pro Ala Ser He Ser Cys Arg Ser Ser Lys Ser Leu Leu His Xaal Asn Xaa2 He Thr Tyr Phe Tyr Trp Tyr Leu Xaa3 Lys Pro Gly Gin Pro Pro Gin Leu Leu He Tyr Gin Met Ser Asn Leu Ala Ser Gly Val Pro Asp Arg Phe Ser Gly Ser Gly Ser Gly Thr Asp Phe Thr Leu Lys He Ser Arg Val Glu Ala Glu Asp Val Gly Val Tyr Tyr Cys Ala Gin Asn Leu Glu Leu Pro Leu Thr Phe Gly Gly Gly Thr Lys Val Glu He Lys (SEQ ID NO: 40),
(a) Xaal is serine (Ser) or arginine (Arg),
(b) Xaa2 is glycine (Gly) or alanine (Ala), and
(c) Xaa3 is glutamine (Gin) or histidine (His).
13. The isolated immunoglobulin light chain polypeptide of claim 12, which comprises the amino acid sequence of SEQ ID NO: 41, SEQ ID NO: 42, SEQ ID NO: 43, or SEQ ID NO: 44.
14. An isolated immunoglobulin light chain polypeptide which comprises the amino acid sequence of Asp He Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr He Thr Cys Arg Ala Ser Gin Xaal He Asn Asn Tyr Leu Asn Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu He Tyr Tyr Thr Ser Xaa2 Leu His Ser Gly Val Pro Ser Arg Phe Ser Xaa3 Ser Gly Ser Gly Xaa4 Asp Xaa5 Thr Phe Thr lie Ser Ser Leu Gin Pro Glu Asp He Ala Thr Tyr Tyr Cys Gin Gin Gly His Thr Leu Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu He Lys Xaa6 Xaa7 (SEQ ID NO: 58), wherein
(a) Xaal is aspartic acid (Asp) or tryptophan (Trp),
(b) Xaa2 is arginine (Arg) or methionine (Met),
(c) Xaa3 is glycine (Gly), serine (Ser) or proline (Pro),
(d) Xaa4 is threonine (Thr) or asparagines (Asn),
(e) Xaa5 is phenylalanine (Phe) or tyrosine (Tyr),
(f) Xaa6 is arginine (Arg) or absent, and
(g) Xaa7 is threonine (Thr) or absent.
15. The isolated immunoglobulin light chain polypeptide of claim 14, wherein the polypeptide comprises the amino acid sequence of Asp He Gin Met Thr Gin Ser Pro Ser Ser Leu Ser Ala Ser Val Gly Asp Arg Val Thr He Thr Cys Arg Ala Ser Gin Asp He Asn Asn Tyr Leu Asn Trp Tyr Gin Gin Lys Pro Gly Lys Ala Pro Lys Leu Leu He Tyr Tyr Thr Ser Arg Leu His Ser Gly Val Pro Ser Arg Phe Ser Xaal Ser Gly Ser Gly Thr Asp Xaa2 Thr Phe Thr lie Ser Ser Leu Gin Pro Glu Asp He Ala Thr Tyr Tyr Cys Gin Gin Gly His Thr Leu Pro Trp Thr Phe Gly Gly Gly Thr Lys Val Glu He Lys (SEQ ID NO: 45), wherein
(a) Xaal is serine (Ser) or proline (Pro), and
(b) Xaa2 is phenylalanine (Phe) or tyrosine (Tyr).
16. The isolated immunoglobulin light chain polypeptide of claim 15, which comprises the amino acid sequence of SEQ ID NO: 46, SEQ ID NO: 47, or SEQ ID NO: 55.
17. An isolated immunoglobulin light chain polypeptide which comprises the amino acid sequence of SEQ ID NO: 48, SEQ ID NO: 49, or SEQ ID NO: 50.
18. An isolated nucleic acid sequence encoding the immunoglobulin heavy chain polypeptide of any one of claims 1-9.
19. An isolated nucleic acid sequence encoding the immunoglobulin light chain polypeptide of any one of claims 10-17.
20. A vector comprising the isolated nucleic acid sequence of claim 18 or claim 19.
21. An interleukin 36 receptor (IL- 36R) -binding agent that exhibits one or more of the following biological activities:
(a) inhibits the interaction between IL-36R and IL-36a, IL-36P, and/or IL- 36γ,
(b) inhibits intracellular signaling mediated by IL-36R,
(c) cross-reacts with and inhibits the activity of human IL-36R, cynomolgus IL-36R, and non-human primate IL-36R.
22. An interleukin 36 receptor (IL-36R)-binding agent comprising the
immunoglobulin heavy chain polypeptide of any one of claims 1-9 and/or the immunoglobulin light chain polypeptide of any one of claims 10-17.
23. The IL-36R-binding agent of claim 21 or claim 22, which comprises the immunoglobulin heavy chain polypeptide of any one of claims 1-9 and the immunoglobulin light chain polypeptide of any one of claims 10-17.
24. The IL-36R-binding agent of claim 21 or claim 22, which comprises the immunoglobulin heavy chain polypeptide of any one of claims 1-9 or the immunoglobulin light chain polypeptide of any one of claims 10-17.
25. The IL-36R-binding agent of any one of claims 21-24, which is an antibody, an antibody conjugate, or an antigen-binding fragment thereof.
26. The IL-36R-binding agent of claim 22, which is a F(ab')2 fragment, a Fab' fragment, a Fab fragment, a Fv fragment, a scFv fragment, a dsFv fragment, a dAb fragment, or a single chain binding polypeptide.
27. An IL-36R-binding agent which competes with the IL-36R binding-agent of any one of claims 18-26 for binding to IL-36R.
28. An isolated nucleic acid sequence encoding the IL-36R-binding agent of any one of claims 21-27.
29. A vector comprising the isolated nucleic acid sequence of claim 28.
30. An isolated cell comprising the vector of claim 29.
31. A composition comprising (a) the IL-36R-binding agent of any one of claims 21-27 or the vector of claim 29 and (b) a pharmaceutically acceptable carrier.
32. A method of treating a disorder in a mammal that is responsive to IL-36R inhibition, which method comprises administering an effective amount of the composition of claim 31 to a mammal having a disorder that is responsive to IL-36R inhibition, whereupon the disorder is treated in the mammal.
33. The method of claim 32, wherein the disorder is an inflammatory disease, an autoimmune disease, a respiratory disease, a metabolic disorder, an epithelial mediated inflammatory disorder, fibrosis, or cancer.
34. The method of claim 33, wherein the disorder is psoriasis vulgaris, pustular psoriasis, generalized pustular psoriasis (GPP), palmo-plantar pustulosis (PPP), inflammatory bowel disease, psoriatic arthritis, multiple sclerosis, rheumatoid arthritis, COPD, scleroderma, asthma, and ankylosing spondylitis.
35. The method of any one of claims 32-34, wherein the half-life of the IL-36R-binding agent in the mammal is between 30 minutes and 45 days.
36. The method of any one of claims 32-35, wherein the IL-36R-binding agent binds to IL-36R with a KD between about 1 picomolar (pM) and about 100 micromolar (μΜ).
37. Use of a composition of claim 31 to prepare a medicament for the treatment of a disorder in a mammal that is responsive to IL-36R inhibition.
38. The use of claim 37, wherein the disorder is an inflammatory disease, an autoimmune disease, a respiratory disease, a metabolic disorder, an epithelial mediated inflammatory disorder, fibrosis, or cancer.
39. The use of claim 37, wherein the disorder is psoriasis vulgaris, pustular psoriasis, generalized pustular psoriasis (GPP), palmo-plantar pustulosis (PPP), inflammatory bowel disease, psoriatic arthritis, multiple sclerosis, rheumatoid arthritis, COPD, scleroderma, asthma, and ankylosing spondylitis.
The reference sequence identification numbers are 100% sequence identical over length and sequence to instant sequence identification numbers.
The claimed invention differs from the prior art in the recitation of a method of treating hidradenitits suppurtiva of claim 1; wherein the subject has increased expression of at least one of an interleukin-36 (IL-36) cytokine, interleukin-36 receptor (IL-36R), or mRNA encoding same in skin affected by the hidradenitis suppurativa of claim 4; and wherein the subject has increased expression of IL-36y in skin affected by the hidradenitis suppurativa of claim 5.
Hessam et al. teaches that IL-36α, IL-36β and IL-36γ were significantly overexpressed in inflamed lesional skin of patients with hidradenitis suppurativa, and there was a dysbalance between the agonistic and antagonistic cytokines in hidradenitis suppurativa skin (Fig. 3). The reference teaches that in psoriasis, a disease characterized by chronic skin inflammation and several histological skin alterations similar to those in hidradenitis suppurativa, IL-36 expression (α, β and γ) has been reported to be enhanced in lesional human skin and in psoriasis mouse models. Furthermore, in IL-36R-deficient mice, psoriasiform dermatitis induced by imiquimod were completely inhibited, suggesting that IL-36 signalling is critical for the control of the IL-23–IL-17–IL-22 axis. Notably, overexpression of the IL-23–Th17 pathway is also seen in hidradenitis suppurativa. The reference teaches the beneficial effects of targeting the IL-36 pathway on skin inflammation by blocking IL-36R and that an antibody against IL-36R has been developed for clinical use in patients with psoriasis. The reference further teaches the potential for targeting IL-36–IL-36R signaling in the therapy of hidradenitis suppurativa.(In particular, first paragraph of discussion to the last paragraph, whole document).
It would have been obvious to one of ordinary skill in the art at the time of invention to have applied the method of treating a disorder that is responsive to IL-36R inhibition including psoriatic arthritis, an epithelial mediated inflammatory disorder, generalized pustular psoriasis (GPP), palmoplantar pustulosis (PPP) and pustular psoriasis comprising administering an effective amount of the IL-36R binding agent of SEQ ID NOs 22 and 44 of Wo 2016/168542 to treating hidradenitis suppurativa as taught by Hessam et al. because Hessam et al. teaches that IL-36α, IL-36β and IL-36γ were significantly overexpressed in inflamed lesional skin of patients with hidradenitis suppurativa and teaches that targeting IL-36–IL-36R signaling using an antibody, like has been effectively done in the treatment of psoriasis, can be performed in the therapy of hidradenitis suppurativa.
From the combined teachings of the references, it is apparent that one of ordinary skill in the art would have had a reasonable expectation of success in producing the claimed invention. Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
22. No claim is allowed.
23. Any inquiry concerning this communication or earlier communications from the examiner should be directed to NORA MAUREEN ROONEY whose telephone number is (571)272-9937. The examiner can normally be reached on M-F from 8:00am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner' s supervisor, Misook Yu, can be reached at telephone number (571) 272-0839. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of an application may be obtained from Patent Center. Status information for published applications may be obtained from Patent Center. Status information for unpublished applications is available through Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free).
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) Form at https://www.uspto.gov/patents/uspto-automated- interview-request-air-form.
September 18, 2026
/Nora M Rooney/
Primary Examiner, Art Unit 1641
Prosecution Insights