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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 9, 2025 has been entered.
Priority
All claims under examination now require administration of HYBRID1. For the reasons set forth in the office action mailed September 11, 2023, the effective filing date of the claimed invention is March 15, 2019 based upon Application No. GB1903608.6.
Claim Interpretation
Claim 1 is drawn to the method of treatment and/or prophylaxis of psoriasis comprising administering to a subject in need thereof an interferon alpha subtype, wherein the interferon alpha subtype is IFNα14 comprising or consisting of an amino acid sequence SEQ ID NO: 1 or a functionally active fragment or variant thereof, or the IFNα10-IFNα14 hybrid (HYBRID 1) comprising or consisting of an amino acid sequence SEQ ID NO: 2 or a functionally active fragment or variant thereof.
The instant specification defines “functionally active” and “fragment” or “variant” on page 7 lines 27-31 and page 21, respectively. Page 5 states that IFNα10 is believed to have greater affinity to IFNR2 and IFNα14 is believed to have greater affinity to IFNR1. Additionally, page 2 lines 3-4 teach that IFNα14 has one of the highest affinities for both of the two interferon receptors. It is understood that the high affinity of IFNα14 and the IFNα10-IFNα14 hybrid to both interferon receptors relative to other IFNα subtypes is responsible for the functional activity of promoting Th1 immune response and suppressing Th2/Th17 immune response. Pages 5-7 provide guidance on substitutions and/or modifications to the IFNα10 or IFNα14 backbones to generate the IFNα10-IFNα14 hybrid. Moreover, the art provides guidance regarding critical residues in the interferon alpha subtypes which confer affinity to IFNR1/IFNR2; see Lavoie et al. (Cytokine. 56: 282-289; Published Online: August 18, 2011).
Regarding the use of IFNα14 and the IFNα10-IFNα14 hybrid for the “prophylaxis” of psoriasis, page 22 of the specification defines prophylaxis as follows:
The treatment may be in respect of psoriasis and the treatment may be prophylactic (preventative treatment). Reference herein to "therapeutic" and "prophylactic" treatment is to be considered in its broadest context. "Prophylactic" does not necessarily mean that the subject will not eventually contract a disease condition. Accordingly, therapeutic and/or prophylactic treatment includes amelioration of the symptoms of a particular allergic condition or preventing or otherwise reducing the risk of developing a particular allergic condition. The term "prophylactic" may be considered as reducing the severity or the onset of a particular condition.
Experiment 1 demonstrates the effect of IFNα14 treatment on normal human skin to reduce the TNF-α-induced secretion of chemokines CXCL1, CXCL5, CXCL8, and CCL20 – which are chemoattractants for neutrophils and dendritic cells. Further, IFNα14 treatment of normal human was demonstrated to promote a Th1 immune response by the production of CCL2, an M2 macrophage chemoattractant, and CCL5, a T-lymphocyte chemoattractant. Experiment 2 demonstrates that in psoriasis-stimulated skin biopsies, IFNα14 reduced the secretion of IL-17, which is known in the art to be involved in the pathogenesis of psoriasis and to stimulate the secretion of CXCL1, CXCL5, CXCL8, and CCL20 by keratinocytes; see Nograles et al. (British Journal of Dermatology. 159: 1092-1102; Published Online: Aug 5, 2008).
Given that prophylaxis is not limited to preventing the development of psoriasis and may be understood as reducing the severity or delaying the onset, and that the disclosure demonstrates a pathologically meaningful inhibition of the production of the chemoattractants CXCL1, CXCL5, CXCL8, and CCL20 by keratinocytes, the disclosure is found to be enabled for the treatment and/or prophylaxis of psoriasis.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 18 and 19 are rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claims 18 and 19, ultimately depend from claim 1, which recites topical administration. Claims 18 and 19 recite other routes of administration and, thus, fail to further limit claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 103
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.
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.
Claims 1, 6, 15, 16, 18, 19, 21, 24, and 25 stand rejected under 35 U.S.C. 103 as being obvious over Stimson (WO 2015/136287; Published: Sep 17, 2015) in view of Elloso et al. (Journal of Leukocyte Biology. 92: 1187-1197; Published: Dec 2012) and Nograles et al. (British Journal of Dermatology. 159: 1092-1102; Published Online: Aug 5, 2008).
Regarding instant claim 1, Stimson claims 1-2 recite a method for the treatment and/or prophylaxis of a of a condition, consisting of an autoimmune disease, an inflammatory disease, allergy or an associated allergic condition and cancer, where an enhancement of a Th1-mediated immune response and suppression of a Th2/Th17-mediated immune response are desired by administering at least one: IFNα10, IFNα14, and a hybrid thereof. Regarding instant claim 25, Figure 7 demonstrates that both IFNα10 and IFNα14 reduced IL-17 secretion by peripheral blood mononuclear cells (PBMCs).
Regarding instant SEQ ID NO: 2 in instant claims 1 and 15, the hybrid taught by Stimson comprises SEQ ID NO: 1 which is 100% homologous to instant SEQ ID NO: 2; see WO 2015/136287 claim 13.
Regarding instant claims 1, 18, and 19, Stimson teaches several suitable routes of administration for the interferon subtypes, including “topical (including buccal and sublingual)”; see page 27. And preferable routes of administration for the interferon subtypes include, but are not limited to, oral, buccal and sublingual – the latter two Stimson et al. groups within topical; see page 27
Regarding instant claims 1 and 16, at pages 38 and 43, Stimson teaches 10 ng/ml of IFNα10 and IFNα14, as well as 1000 IU/ml of IFNα10 and IFNα14. Further, Figure 14 of Stimson demonstrates that 100 IU/ml of IFNα14 significantly reduces IL-17.
Regarding instant claim 21, Stimson teaches daily administration; see page 29 lines 19-25.
Stimson does not teach the use of IFNα14 nor the IFNα10-IFNα14 hybrid in the treatment and/or prophylaxis of psoriasis. Nor does Stimson teach that IFNα14 or the IFNα10-IFNα14 hybrid can suppress or inhibit CXCL1, CXCL8, CXCL5, or CCL20.
Elloso et al. teaches (page 1188) that psoriasis is an inflammatory and autoimmune disease with a pathology characterized by aberrant IL-17 signaling. The significance of Th17 signaling in psoriasis is evidenced by the increased expression of IL-17 and IL-17-related cytokines and increased number of IL-17 producing cells found within psoriatic lesions. Moreover, the overexpression of IL-17 and IL-17-related cytokines within lesions further drives the recruitment of proinflammatory cytokine producing cells further promoting chronic inflammation (Elloso et al., page 1188).
Neither Stimson nor Elloso et al. teach suppressing or inhibiting CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 from keratinocytes.
Regarding instant claims 1 and 24, Nograles et al. teaches that CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 expression by keratinocytes is induced in response to IL-17 treatment; see Figure 4.
Given that Stimson teaches treating Th17-mediated diseases including autoimmune diseases, that the instant disclosure teaches psoriasis is an autoimmune disease characterized by “an exaggerated Th17 response” (see instant page 1), and that Elloso further supports that psoriasis is a Th17-mediated autoimmune disease, a person of skill in the art would have been motivated to apply the method taught by Stimson to psoriasis patients with a reasonable expectation of success. Moreover, it would be obvious to one of ordinary skill in the art to combine elements of the method taught by Stimson using IFNα14 or HYBRID1 for same purpose - the treatment and/or prophylaxis of an autoimmune disease characterized by “an exaggerated Th17 response,” such as psoriasis. Section 2144.06 of the MPEP provides guidance as to obviousness of art recognized equivalents for the same purpose. The court has held that it is obvious to combine two elements each of which is taught by the prior art to be useful for the same purpose. No specific teaching or suggestion is needed for combination – the idea of combining them flows logically from their having been individually taught in the prior art as useful for the same purpose. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Moreover, instant claim 6 recites the limitation that the psoriasis presents as mild, mild-to- moderate, moderate, moderate-to-severe or severe by Psoriasis Area and Severity Index (PASI) score. Given this range encompasses all severity rankings by PASI, use in psoriasis generally would be encompassed in instant claim 6; therefore, it is rejected as described above.
Regarding claim 25, Stimson does not teach a reduction in IL-17 in the dermal layer; however, PBMCs are known to be recruited into the dermis during wound healing and one would reasonably expect that, especially when applied topically to the skin, IFNα14 or the IFNα10-IFNα14 hybrid would reduce IL-17 expression in the dermal layers. Given the effects of IFNα14 treatment on IL-17 secretion demonstrated in Stimson Figure 7, it would have been obvious to one of ordinary skill in the art and one would have a reasonable expectation of success that IFNα14 or the IFNα10-IFNα14 hybrid would reduce IL-17 in the dermal layers.
Regarding suppressing CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 from keratinocytes, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success that inhibiting or reducing the expression of IL-17 by administering IFNα14 or the IFNα10-IFNα14 hybrid taught by Stimson to reduce the expression of IL-17 would result in a reduction of CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 given that Nograles teaches those chemokines are induced by keratinocytes in response to IL-17. Regarding the magnitude of reduction in claim 24, Figure 3 of Nograles et al. demonstrates that IL-17 induced a 7.69-fold increase in CXCL1 secretion, for example, from keratinocytes and Figure 7 Stimson demonstrates a dose-dependent decrease in IL-17 secretion by PBMCs following IFNα14 treatment. One of ordinary skill in the art would recognize the decrease in secretion of CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 from keratinocytes would flow naturally from treatment with an agent demonstrated to reduce IL-17 production and the magnitude of that decrease in CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 secretion would be dependent on the dose IL-17-reducing agent (IFNα14 or the IFNα10-IFNα14 hybrid) administered.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1, 6, 15, 16, 18, 19, 21, 24, and 25 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 11-12, and 15-16 of U.S. Patent No. 9522173 B2 in view of Stimson (WO 2015/136287; Published: Sep 17, 2015), Elloso et al. (Journal of Leukocyte Biology. 92: 1187-1197; Published: Dec 2012), and Nograles et al. (British Journal of Dermatology. 159: 1092-1102; Published Online: Aug 5, 2008). Although the claims at issue are not identical, they are not patentably distinct from each other.
U.S. Patent No. 9522173 B2 is drawn to the methods of treating a condition where an enhancement of a Th1-mediated immune response and suppression of a Th2/Th17-mediated immune response are desired or an autoimmune disease, an inflammatory disease and allergy or an associated allergic condition with at least one interferon alpha subtype selected from IFNα10 and IFNα14 (US 9522173 claims 1, 11, 12, and 16; instant claims 1 and 6. Given the definition of functional variant in the instant specification (page 7 line 27 - page 8 line 20) as having at least 70% homology and comprising the binding sites of IFNα10 and IFNα14, IFNα14 recited in the ‘173 claims reasonably comprises a functional variant. Instant HYBRID1 is 90.7% homologous to IFNα14. See the alignment below where IFNα14 is the Qy line and HYBRID1 is the Db line.
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The claims of US 9522173 B2 does not teach administering the IFNα14 or the IFNα10-IFNα14 hybrid for the treatment of psoriasis. Nor do the claims teach a dose regimen nor the effect on CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 expression by keratinocytes.
Regarding instant claim 1, Stimson claims 1-2 recite a method for the treatment and/or prophylaxis of a of a condition, consisting of an autoimmune disease, an inflammatory disease, allergy or an associated allergic condition and cancer, where an enhancement of a Th1-mediated immune response and suppression of a Th2/Th17-mediated immune response are desired by administering at least one: IFNα10, IFNα14, and a hybrid thereof. Regarding instant claim 25, Figure 7 demonstrates that both IFNα10 and IFNα14 reduced IL-17 secretion by peripheral blood mononuclear cells (PBMCs).
Regarding instant SEQ ID NO: 2 in instant claims 1 and 15, the hybrid taught by Stimson comprises SEQ ID NO: 1 which is 100% homologous to instant SEQ ID NO: 2; see WO 2015/136287 claim 13.
Regarding instant claims 1, 18, and 19, Stimson teaches several suitable routes of administration for the interferon subtypes, including “topical (including buccal and sublingual)”; see page 27. And preferable routes of administration for the interferon subtypes include oral, buccal and sublingual – the latter two Stimson et al. groups within topical; see page 27
Regarding instant claims 1 and 16, at pages 38 and 43, Stimson teaches 10 ng/ml of IFNα10 and IFNα14, as well as 1000 IU/ml of IFNα10 and IFNα14, which are within the range recited in claim 5 and included in claim 16. Further, Figure 14 of Stimson demonstrates that 100 IU/ml of IFNα14 significantly reduces IL-17.
Regarding instant claim 21, Stimson teaches daily administration; see page 29 lines 19-25.
Stimson does not teach the use of IFNα14 nor the IFNα10-IFNα14 hybrid in the treatment and/or prophylaxis of psoriasis. Nor does Stimson teach that IFNα14 or the IFNα10-IFNα14 hybrid can suppress or inhibit CXCL1, CXCL8, CXCL5, or CCL20.
Elloso et al. teaches (page 1188) that psoriasis is an inflammatory and autoimmune disease with a pathology characterized by aberrant IL-17 signaling. The significance of Th17 signaling in psoriasis is evidenced by the increased expression of IL-17 and IL-17-related cytokines and increased number of IL-17 producing cells found within psoriatic lesions. Moreover, the overexpression of IL-17 and IL-17-related cytokines within lesions further drives the recruitment of proinflammatory cytokine producing cells further promoting chronic inflammation (Elloso et al., page 1188).
Neither Stimson nor Elloso et al. teach suppressing or inhibiting CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 from keratinocytes.
Regarding instant claims 1 and 24, Nograles et al. teaches that CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 expression by keratinocytes is induced in response to IL-17 treatment; see Figure 4.
Given that the claims of US 9522173 B2 teach treating Th17-mediated diseases including autoimmune diseases, that the instant disclosure teaches psoriasis is an autoimmune disease characterized by “an exaggerated Th17 response” (see instant page 1), and that Elloso further supports that psoriasis is Th17-mediated autoimmune disease, a person of skill in the art would have been motivated to apply the method taught by the claims of US 9522173 B2 to psoriasis patients with a reasonable expectation of success. Moreover, it would be obvious to one of ordinary skill in the art to combine elements of the method taught by the claims of US 9522173 B2 and supported by Stimson using IFNα14 or HYBRID1 for same purpose - the treatment and/or prophylaxis of an autoimmune disease characterized by “an exaggerated Th17 response,” such as psoriasis. Section 2144.06 of the MPEP provides guidance as to obviousness of art recognized equivalents for the same purpose. The court has held that it is obvious to combine two elements each of which is taught by the prior art to be useful for the same purpose. No specific teaching or suggestion is needed for combination – the idea of combining them flows logically from their having been individually taught in the prior art as useful for the same purpose. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Moreover, instant claim 6 recites the limitation that the psoriasis presents as mild, mild-to- moderate, moderate, moderate-to-severe or severe by Psoriasis Area and Severity Index (PASI) score. Given this range encompasses all severity rankings by PASI, use in psoriasis generally would be encompassed in instant claim 6; therefore, it is rejected as described above.
Regarding instant claim 25, the claims of US 9522173 B2 does not teach a reduction in IL-17 in the dermal layer; however, PBMCs are known to be recruited into the dermis during wound healing and one would reasonably expect that, especially when applied topically to the skin, IFNα14 or the IFNα10-IFNα14 hybrid would reduce IL-17 expression in the dermal layers. Given the effects of IFNα14 treatment on IL-17 secretion demonstrated in Stimson Figure 7, it would have been obvious to one of ordinary skill in the art and one would have a reasonable expectation of success that IFNα14 or the IFNα10-IFNα14 hybrid would reduce IL-17 in the dermal layers.
Regarding suppressing CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 from keratinocytes, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success that inhibiting or reducing the expression of IL-17 by administering IFNα14 as taught by the claims of US 9522173 B2 or the IFNα10-IFNα14 hybrid to reduce the expression of IL-17 would result in a reduction of CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 given that Nograles teaches those chemokines are induced by keratinocytes in response to IL-17. Regarding the magnitude of reduction in claim 24, Figure 3 of Nograles et al. demonstrates that IL-17 induced a 7.69-fold increase in CXCL1 secretion, for example, from keratinocytes and Figure 7 Stimson demonstrates a dose-dependent decrease in IL-17 secretion by PBMCs following IFNα14 treatment. One of ordinary skill in the art would recognize the decrease in secretion of CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 from keratinocytes would flow naturally from treatment with an agent demonstrated to reduce IL-17 production and the magnitude of that decrease in CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 secretion would be dependent on the dose IL-17-reducing agent (IFNα14 or the IFNα10-IFNα14 hybrid) administered.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Claims 1, 6, 15, 16, 18, 19, 21, 24, and 25 stand rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-2 and 8 of U.S. Patent No. 11267860 B2 in view of Stimson (WO 2015/136287; Published: Sep 17, 2015), Elloso et al. (Journal of Leukocyte Biology. 92: 1187-1197; Published: Dec 2012), and Nograles et al. (British Journal of Dermatology. 159: 1092-1102; Published Online: Aug 5, 2008). Although the claims at issue are not identical, they are not patentably distinct from each other.
U.S. Patent No. 11267860 B2 (claims 1-2) recites the method for enhancing Th1-mediated immune response and suppressing a Th2/17-mediated immune response in a subject suffering from an autoimmune disease, an inflammatory disease, an allergy, an allergic disease, or a cancer by administering an IFNα10-IFNα14 hybrid comprising SEQ ID NO: 1. U.S. Patent No. 11267860 B2 SEQ ID NO: 1 and the instant applications SEQ ID NO: 2 (instant claims 1 and 15), of which HYBRID1 is comprised, match with 100% identity. In claim 8, U.S. Patent No. 11267860 B2 further claims administering an IFNα10-IFNα14 hybrid comprising SEQ ID NO: 1 for suppressing IL-17 expression in a subject having a condition mediated by enhanced expression of IL-17. In the instant disclosure (page 1), Applicant states that “an exaggerated Th17 response may lead to severe inflammatory responses and autoimmune diseases, such as psoriasis” and that “Th17 cells produce interleukin-17 (IL17).” Together, psoriasis (instant claims 1 and 6) is both an autoimmune disease (US 11267860 B2 claim 2) and a condition mediated by enhanced expression of IL-17 (US 11267860 B2 claim 8).
The claims of US 11267860 B2 does not teach administering the IFNα14 or the IFNα10-IFNα14 hybrid for the treatment of psoriasis. Nor do the claims teach a dose regimen nor the effect on CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 expression by keratinocytes.
Regarding instant claim 1, Stimson claims 1-2 recite a method for the treatment and/or prophylaxis of a of a condition, consisting of an autoimmune disease, an inflammatory disease, allergy or an associated allergic condition and cancer, where an enhancement of a Th1-mediated immune response and suppression of a Th2/Th17-mediated immune response are desired by administering at least one: IFNα10, IFNα14, and a hybrid thereof. Regarding instant claim 25, Figure 7 demonstrates that both IFNα10 and IFNα14 reduced IL-17 secretion by peripheral blood mononuclear cells (PBMCs).
Regarding instant SEQ ID NO: 2 in instant claims 1 and 15, the hybrid taught by Stimson comprises SEQ ID NO: 1 which is 100% homologous to instant SEQ ID NO: 2; see WO 2015/136287 claim 13.
Regarding instant claims 1, 18, and 19, Stimson teaches several suitable routes of administration for the interferon subtypes, including “topical (including buccal and sublingual)”; see page 27. And preferable routes of administration for the interferon subtypes include oral, buccal and sublingual – the latter two Stimson et al. groups within topical; see page 27
Regarding instant claims 1 and 16, at pages 38 and 43, Stimson teaches 10 ng/ml of IFNα10 and IFNα14, as well as 1000 IU/ml of IFNα10 and IFNα14, which are within the range recited in claim 5 and included in claim 16. Further, Figure 14 of Stimson demonstrates that 100 IU/ml of IFNα14 significantly reduces IL-17.
Regarding instant claim 21, Stimson teaches daily administration; see page 29 lines 19-25.
Stimson does not teach the use of IFNα14 nor the IFNα10-IFNα14 hybrid in the treatment and/or prophylaxis of psoriasis. Nor does Stimson teach that IFNα14 or the IFNα10-IFNα14 hybrid can suppress or inhibit CXCL1, CXCL8, CXCL5, or CCL20.
Elloso et al. teaches (page 1188) that psoriasis is an inflammatory and autoimmune disease with a pathology characterized by aberrant IL-17 signaling. The significance of Th17 signaling in psoriasis is evidenced by the increased expression of IL-17 and IL-17-related cytokines and increased number of IL-17 producing cells found within psoriatic lesions. Moreover, the overexpression of IL-17 and IL-17-related cytokines within lesions further drives the recruitment of proinflammatory cytokine producing cells further promoting chronic inflammation (Elloso et al., page 1188).
Neither Stimson nor Elloso et al. teach suppressing or inhibiting CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 from keratinocytes.
Regarding instant claims 1 and 24, Nograles et al. teaches that CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 expression by keratinocytes is induced in response to IL-17 treatment; see Figure 4.
Given that the claims of US 11267860 B2 teach treating Th17-mediated diseases including autoimmune diseases, that the instant disclosure teaches psoriasis is an autoimmune disease characterized by “an exaggerated Th17 response” (see instant page 1), and that Elloso teaches that psoriasis is such a disease, a person of skill in the art would have been motivated to apply the method taught by the claims of US 11267860 B2 to psoriasis patients with a reasonable expectation of success. Moreover, it would be obvious to one of ordinary skill in the art to combine elements of the method taught by the claims of US 11267860 B2 and supported by Stimson using IFNα14 or HYBRID1 for same purpose - the treatment and/or prophylaxis of an autoimmune disease characterized by “an exaggerated Th17 response,” such as psoriasis. Section 2144.06 of the MPEP provides guidance as to obviousness of art recognized equivalents for the same purpose. The court has held that it is obvious to combine two elements each of which is taught by the prior art to be useful for the same purpose. No specific teaching or suggestion is needed for combination – the idea of combining them flows logically from their having been individually taught in the prior art as useful for the same purpose. See In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980).
Moreover, instant claim 6 recites the limitation that the psoriasis presents as mild, mild-to- moderate, moderate, moderate-to-severe or severe by Psoriasis Area and Severity Index (PASI) score. Given this range encompasses all severity rankings by PASI, use in psoriasis generally would be encompassed in instant claim 6; therefore, it is rejected as described above.
Regarding instant claim 25, the claims of US 11267860 B2 does not teach a reduction in IL-17 in the dermal layer; however, PBMCs are known to be recruited into the dermis during wound healing and one would reasonably expect that, especially when applied topically to the skin, IFNα14 or the IFNα10-IFNα14 hybrid would reduce IL-17 expression in the dermal layers. Given the effects of IFNα14 treatment on IL-17 secretion demonstrated in Stimson Figure 7, it would have been obvious to one of ordinary skill in the art and one would have a reasonable expectation of success that IFNα14 or the IFNα10-IFNα14 hybrid would reduce IL-17 in the dermal layers.
Regarding suppressing CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 from keratinocytes, it would have been obvious to one of ordinary skill in the art and one would have had a reasonable expectation of success that inhibiting or reducing the expression of IL-17 by administering IFNα14 or the IFNα10-IFNα14 hybrid as taught by the claims of US 11267860 B2 and Stimson to reduce the expression of IL-17 would result in a reduction of CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 given that Nograles teaches those chemokines are induced by keratinocytes in response to IL-17. Regarding the magnitude of reduction in claim 24, Figure 3 of Nograles et al. demonstrates that IL-17 induced a 7.69-fold increase in CXCL1 secretion, for example, from keratinocytes and Figure 7 Stimson demonstrates a dose-dependent decrease in IL-17 secretion by PBMCs following IFNα14 treatment. One of ordinary skill in the art would recognize the decrease in secretion of CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 from keratinocytes would flow naturally from treatment with an agent demonstrated to reduce IL-17 production and the magnitude of that decrease in CXCL1, CXCL8 (IL-8), CXCL5, and CCL20 secretion would be dependent on the dose IL-17-reducing agent (IFNα14 or the IFNα10-IFNα14 hybrid) administered.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art
before the effective filing date of the application, as evidenced by the references.
Response to Arguments
Applicant’s amendments filed December 9, 2025 are acknowledged. Any rejection not repeated above is resolved by amendment.
Applicant’s arguments filed December 9, 2025, with respect to the rejection(s) of claim(s) 1, 6, 15, 16, 18, 19, 21, 24, and 25 under 35 U.S.C. 103 and nonstatutory double patenting have been fully considered and are not persuasive.
Applicant asserts on page 8 that the instant invention satisfies an unmet need. Applicant states that “topical medications have limited efficacy and are not suitable for long-term use; there have been no new topical medications to treat psoriasis in over twenty-five years; and systemic biological drugs are effective [but] may cause a range of harmful side-effects associated with reduced ability to fight [infection]. Thus, there is a significant unmet need for an effective, safe, topical treatment that can be used to treat the majority of psoriasis patients” Applicant references page 3 lines 15-22 of the Specification for support, but does not provide any objective evidence that 1. an art recognized problem existed in the art for a long period of time without solution, 2. the long-felt need had not been satisfied by another before the instant invention, and 3. the invention satisfies the long-felt need; see MPEP 716.04. Moreover, the data presented in the instant disclosure does not support that the instant invention is an effective, safe, topical treatment that can be used to treat the majority of psoriasis patients or is suitable for long-term use.
Applicant asserts that it is unexpected that IFN-α14 would pass through skin and that IFN-α14 would effect chemokine expression by keratinocytes when administered topically and IFN-α14 or HYBRID 1 results in a greater reduction or inhibition of CXCL1, CXCL8, CXCL5, and CCL20 in keratinocytes compared to previous topical medications.
Examiner disagrees. It is not unexpected that IFN-α14 would pass through the skin. In fact, Stimson et al. teaches that IFN-α10, IFN-α14, or a hybrid thereof may be administered topically; see page 27. Moreover, Stimson et al. teaches the use microspheres, liposomes, other microparticulate delivery systems; see page 28. King et al. (European Journal of Pharmaceutics and Biopharmaceutics. 84: 532-539; Published: March 14, 2013) evidences that, similarly sized, human IFN-α2b (~19kDa) can be administered topically via lipid-based delivery system. Further, instant claim 1 does not exclude the use of lipid-based delivery systems nor is it limited to the administration of IFN-α14. Thus, the alleged unexpected result is also not commensurate with the scope of the claims; see MPEP 716.02(d).
Stimson et al. Example 6 teaches that IFN-α14 suppressed CXCL1, CXCL8, CXCL5, and CCL20 expression in mononuclear cells. No evidence or rationale as why a similar response in keratinocytes would be unexpected has been provided.
Finally, Applicant asserts that the IFN-α14 or HYBRID1 outperformed existing topical treatments, but no data supporting this conclusion was found in the instant disclosure nor arguments.
Further, MPEP 716.01(c), “[t]o be of probative value, any objection evidence should be supported by actual proof. Objective evidence which must be factually supported by an appropriate affidavit or declaration to be of probative value includes evidence of unexpected results, commercial success, solution of a long-felt need, inoperability of the prior art, invention before the date of the reference, and allegations that the author(s) of the prior art derived the disclosed subject matter from the inventor or at least one joint inventor. See, for example, In re De Blauwe, 736 F.2d 699, 705, 222 USPQ 191, 196 (Fed. Cir. 1984) (“It is well settled that unexpected results must be established by factual evidence.” “[A]ppellants have not presented any experimental data showing that prior heat-shrinkable articles split. Due to the absence of tests comparing appellant’s heat shrinkable articles with those of the closest prior art, we conclude that appellant’s assertions of unexpected results constitute mere argument.”).” The evidence, while allegedly probative, is not properly filed in an affidavit or declaration. Therefore, the veracity of the evidence is not supported by the manner of Applicant’s submission.
Applicant states that Stimson et al. neither teaches nor suggests the topical administration of an interferon alpha subtype for the treatment and/or prophylaxis of psoriasis. It is correct that Stimson et al. does not specifically teach every limitation in claim 1 and deficiencies are addressed by Elloso et al. and Nograles et al. as set forth in the rejection under 35 U.S.C. 103 above. Additionally, Applicant states that Stimson et al. teaches toward oral administration on page 23 where Stimson et al. teaches an enhanced response when administered orally. This finding appears to come from Example 3 of Stimson et al. where mice were given IFN-α14 by oral (buccal) and intraperitoneal injection administration along with ovalbumin, a common oral allergen, to evaluate IFN-α14 as an adjuvant. While the finding might teach towards oral administration of IFN-α14 in conjunction with food allergen tolerization, the Example does not teach away from topical administration for other conditions.
Regarding the double patenting rejections over the claims of U.S. Patent No. 9522173 B2 and 11267860 B2, Applicant argues that the neither patent claims a method of treating psoriasis by topical administration and, thus, the rejections should be withdrawn.
This is unpersuasive. The double patenting rejections further cite Stimson et al., Elloso et al., and Nograles et al. to address psoriasis and topical administration. The nonstatutory double patenting rejections are maintained.
Conclusion
All claims are identical to or patentably indistinct from, or have unity of invention with claims in the application prior to the entry of the submission under 37 CFR 1.114 (that is, restriction (including a lack of unity of invention) would not be proper) and all claims could have been finally rejected on the grounds and art of record in the next Office action if they had been entered in the application prior to entry under 37 CFR 1.114. Accordingly, THIS ACTION IS MADE FINAL even though it is a first action after the filing of a request for continued examination and the submission under 37 CFR 1.114. See MPEP § 706.07(b). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
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/KATHERINE ANN HOLTZMAN/Examiner, Art Unit 1644
/JULIET C SWITZER/Primary Examiner, Art Unit 1682