DETAILED ACTION
Claim Status
The amendment filed 07/ 01/26 is acknowledged. Claims 2, 4, 7, 12, 14-24, 32-61, 70, and 71 are cancelled. Claims 1, 3, 5, 6, 8-10, 62, 65, and 72 are cancelled. Claims 1, 3, 5, 6, 8-11, 13, 25-31, 62-69, and 72-75 are pending and under examination.
Withdrawn Rejections
The rejection of claim 62 under 35 U.S.C. 112(a) as failing to comply with the enablement requirement is withdrawn in view of the amendment to claim 62.
The rejection of claims 1, 2, 4, 5, 7, 8, 10, 25, 27, 30, 31, 62-69, 72, and 73 under 35 U.S.C. 103 as being unpatentable over Fu et al., WO2018236701A1 is withdrawn in view of applicant arguments.
The rejection of claims 3, 6, 9, 11, and 13 under 35 U.S.C. 103 as being unpatentable over Fu et al. in view of Liu et al. (2017) is withdrawn in view of applicant arguments.
The rejection of claims 15, 17, and 26 under 35 U.S.C. 103 as being unpatentable over Fu et al. in view of Faust et al. (2020) is withdrawn in view of applicant arguments.
The rejection of claims 28 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Fu et al. in view of Thomas et al. (2011) is withdrawn in view of applicant arguments.
New Rejections
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 26 and 27 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.
Claim 26 recites the limitation "an additional IFN moiety masked by an additional IFNAa1.” There is insufficient antecedent basis for this limitation in the claim as amended claim 1 does not recite a first masked IFN moiety.
Claim 27 recites the term “at least about,” which is a relative term that renders the claim indefinite. The term “at least about” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and it is unclear exactly what the lower bound for the claimed ranges are. As such, one of ordinary skill in the art would not be able to ascertain the scope of the claim with reasonable certainty.
Therefore, claims 26 and 27 are rejected under 35 U.S.C. 112(b) as being indefinite.
Claim Rejections - 35 USC § 103
Claims 1, 3, 5, 6, 8-11, 13, 25-27, 30, 31, 62-69, 72, and 73 are rejected under 35 U.S.C. 103 as being unpatentable over Fu et al., WO2018236701A1, in view of Smith et al., US7732167B2.
Independent claim 1 is drawn to an interferon receptor agonist comprising an Fc domain, a type 1 IFN moiety, an IFNaR1 moiety, and an IFNaR2 moiety. Claims 3, 5, 6, 8-11, 13, 25-27, 30, and 31 include specific structural configurations and sequence variants. Claims 62-65 are drawn to nucleic acids encoding said agonist, host cells, methods of producing, and a pharmaceutical composition. Claims 66-69, 72, and 73 are drawn to methods of administering.
Fu et al. discloses a human interferon prodrug comprising an IFNaR domain, which may be either IFNaR1 or IFNaR2 [see claims 8 and 9], one or more Type 1 interferon (IFN) domains [see claims 1 and 4], which may be IFN-a, IFN-β, IFN-K, IFN-δ, IFN- ε, IFN-τ, IFN-ω or IFN-ζ [see claim 10], that retains interferon activity when not engaged by the IFNaR domain [see claim 1], and an Ig Fc domain [see claim 1] (instant claim 1). The Fc domain may be an IgG [see claim 2], which inherently discloses a dimeric Fc structure comprising a first polypeptide chain comprising an Fc domain and a second polypeptide chain comprising a second Fc domain associated with the first as an Fc domain requires two polypeptide chains, and additionally, Fu et al. teaches that Fc domains are useful because of their ability to dimerize and generate constructs comprising up to four interferons [see p. 12, par. 1] (instant claim 1). Fu et al. discloses that the INFaR domain is fused to the N-terminal of the IFN domain via a protease-cleavable linker, functionally unmasking the IFN when cleaved, and that the IFN domain is fused to the N-terminal of the Fc domain via a second linker [see claims 1 and 6] (instant claims 5, 8, 10, 13, and 25). Fu et al. demonstrates the activity of the prodrug using purified human IFNaR1 or IFNaR2 extracellular domains in combination with a human IFNa2-Fc [see specification, p.45, par. 2], and although Fu et al. does not explicitly disclose the IFNa2 subtype, the most well-known and commercialized are IFNa2a and IFNa2b, which differ from one another by a single amino acid at residue 23 but utilize the same IFNaR signaling pathway [see Paul et al., p. 2, par. 4]. As such, it would have been reasonably understood that Fu et al. utilized either hIFNa2b or hIFNa2a when teaching the use of IFNa2 (instant claim 27). The human IFNaR1 extracellular domain necessarily comprises SD1-SD4 and the IFNR2 extracellular domain necessarily comprises D1 and D2, implicitly requiring the natural human sequences encoding their structures (instant claims 30 and 31). Fu et al. teaches that the prodrug may contain two copies of the IFN domain and further teaches that heterodimeric constructs may contain two or even four different type I interferons, and describes an FcA-FcB heterodimer in which a blocking receptor and an interferon may be fused to each of FcA or FcB [see p.12, par. 1] (instant claim 26). Nucleic acid constructs encoding the prodrug [see claim 11] (instant claim 62), recombinant cells engineered to express the prodrug [see claim 21] (instant claim 63), and methods of recovering the prodrug from procaryotic or eucaryotic expression system are disclosed [see p.24, par. 2] (instant claim 64). The prodrug may be formulated and administered with a pharmaceutically acceptable excipient [see p.25, par. 3] (instant claim 65) as a treatment for cancer [see claim 25] (instant claim 66) and can be delivered via any conventional route [see p.26, par. 4] (instant claim 73), including local administration, wherein the linker is selectively cleavable by a protease overexpressed in the tumor microenvironment (instant claims 67 and 68) to reduce systemic toxicity [see p.7 par. 2] (instant claim 69). Finally, Fu et al. notes the potential use of the prodrug in combination with additional advanced interferon therapy formats, such as antibody-cytokine bispecific fusion proteins [see p.8, par. 1] (instant claim 72).
Fu et al. does not teach or suggest an embodiment wherein IFNaR1 and IFNaR2 are both present on the same polypeptide.
Smith et al. teaches interferon-binding fusion proteins comprising both an IFNaR1-derived component (R1) and an IFNAR2-dereived component (R2) within a single polypeptide chain comprising an additional fusion component (F) [see col. 1, par. 4, lines 29-36], which may be an Fc domain [see col. 2, par. 4, lines 33-36] (instant claim 1). Smith et al. teaches that the R1 and R2 components may be arranged in different orders within the fusion protein, including F-R1-R2, R1-F-R2, and R2-R1-F [see col. 1, par. 3-4] (instant claims 3, 6, 9, 11] and that there may be a plurality of each component [see col. 1, par. 4, line 35] (instant claim 26). Smith et al. teaches that the claimed compositions inhibit interferon activity [see col. 1, par. 2].
It would have been obvious to one of ordinary skill in the art to modify the prodrug of Fu et al. to include both IFNaR1 and IFNaR2 in the same polypeptide chain with an IFN moiety as Smith et al. teaches that IFNaR1 and IFNaR2-derived components may be combined into the same polypeptide while maintaining activity, Fu et al. similarly teaches that both components mask IFN, and it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art to be useful [see In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). This composition would constitute a monovalent construct as each component has a single copy present (instant claims 74 and 75). Accordingly, there would have been a reasonable expectation of success that both receptor moieties would be incorporated into a single polypeptide chain and retain their interactions as this modification would have constituted combining known elements for their known use through known and routine techniques in the art of fusion proteins.
Regarding claim 3, it would have been obvious to place the components C-terminal to the first Fc domain as Smith et al. teaches that Fc domains are a modular platform that can tolerate N- or C-terminal placement and specifically identifies F-R1-R2 as one arrangement of the fusion protein. Arriving at the claimed arrangement would have been a matter of routine optimization, requiring identifying one of a limited set of possible arrangements when utilizing the Fc-terminal orientations taught by Smith et al. in combination with Fu et al.’s disclosed receptor/IFN interaction and masking.
Similarly, regarding claims 6, 9, 11, 13, 74, and 75, the art collectively teaches that the orientation of the IFN and the receptor components within the monovalent and multivalent compositions were recognized structural variables and also teaches placing linkers between each of said components, and as such it would have been obvious to investigate alternative orientations of the moieties as a matter of routine optimization well within the skill of an ordinary artisan, particularly given that the polypeptide comprises four components and therefore a limited number of possible orientations. There would have been a reasonable expectation of success as the combined teachings convey that the components can be rearranged while maintaining their binding/masking properties.
Regarding claim 26, as discussed above, both Fu et al. and Smith et al. teach multivalent constructs on a single polypeptide chain as well as distributed across Fc-associated polypeptides. As such, it would have been obvious to generate a bivalent construct comprising an additional masked IFN moiety comprising an IFNaR1 and IFNaR2 as Fu et al. teaches receptor masked interferons on different polypeptide chains of an Fc-associated multimeric construct and Smith et al. similarly teaches multimeric peptides comprising two or more R1/R2 domains using Fc as a suitable multimerizing component (instant claim 26).
Therefore, claims 1, 3, 5, 6, 8-11, 13, 25-27, 30, 31, 62-69, 72, and 73 are rejected under 35 U.S.C. 103.
Claims 1, 28, and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Fu et al., WO2018236701A1, in view of Smith et al., US7732167B2, and further in view of Paul et al. and Thomas et al. (2011).
The disclosure of Fu et al. and Smith et al. are discussed above.
The combination of these references does not teach or suggest the particular attenuating mutations or sequence variants recited in the claims.
Thomas et al. discloses how different IFN subtypes bind differently to IFNaR1 and IFNaR2, specifically disclosing key point mutations to IFNa2 including L26A, L30A, and R149A, that contribute to receptor interaction [see p. 627, Probing Differential IFN Signaling with Structure-Based Mutational Analysis] (instant claims 28 and 29). Thomas et al. teaches that the L26A and L30A are within a hydrophobic interaction cluster at the binding interface with IFN that is common to both IFNa2a and IFNa2b [see p. 652, col. 1, par. 1, lines 27-32] and also teaches that R149A is conserved across all IFN subtypes except IFNw [see p. 652, col. 1, par. 2].
It would have been obvious to combine these teachings and introduce the point mutations disclosed by Thomas et al. into the modified prodrug of Fu et al. to modulate the masking strength of the IFNaRs as Thomas et al. teaches that introducing these mutations into IFNa2 modifies receptor binding strength, Fu et al. teaches the functional masking of IFNa2, and Fu et al. further teaches unmasking at target sites. There would have been a reasonable expectation of success as Thomas et al. teaches that the mutations are within a region common to both IFNa2a and IFNa2b, both subtypes bind the same target, and the methods of inducing the relevant mutations are well known and routine in the art.
Therefore, claims 1, 28, and 29 are rejected under 35 U.S.C. 103.
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.
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Claims 1, 26, 27, 30, 31, 62-69, 72, and 73 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 5 of U.S. Patent No. US7732167B2 in view of Fu et al. and in further view of Paul et al.
US7732167B2 teaches a fusion protein consisting of R2, R1, and F, in the N to C-terminus direction, wherein R2 consists of amino acids 35-233 of SEQ ID NO: 4, R1 consists of amino acids 28-335 of SEQ ID NO: 2, and F consists of an immunoglobulin-derived domain selected from the group consisting of an Fc domain of IgG and a heavy chain of IgG. The claimed portions of SEQ ID NOs: 4 and 2 correspond to the extracellular domains of IFNaR2 and IFNaR1 respectively [as evidenced by US7732167B2, specification, col. 7, par. 1]. US7732167B2 teaches a nucleic acid encoding the fusion protein, a host cell comprising the fusion protein, and a method of making the fusion protein comprising culturing host cells to express the protein and then recovering the protein from the cells [see claim 5].
US7732167B2 does not teach or suggest incorporating an IFN moiety into the construct.
Fu et al. discloses a human interferon prodrug comprising an IFNaR extracellular domain, which may be either IFNaR1 or IFNaR2 [see claims 8 and 9], one or more Type 1 interferon (IFN) domains [see claims 1 and 4], which may be IFN-a, IFN-β, IFN-K, IFN-δ, IFN- ε, IFN-τ, IFN-ω or IFN-ζ [see claim 10], that retains interferon activity when not engaged by the IFNaR domain [see claim 1], and an Ig Fc domain [see claim 1] (instant claim 1). The Fc domain may be an IgG [see claim 2], which inherently discloses a dimeric Fc structure comprising a first polypeptide chain comprising an Fc domain and a second polypeptide chain comprising a second Fc domain associated with the first as an Fc domain requires two polypeptide chains, and additionally, Fu et al. teaches that Fc domains are useful because of their ability to dimerize and generate constructs comprising up to four interferons [see p. 12, par. 1] (instant claim 1). Fu et al. discloses that the INFaR domain is fused to the N-terminal of the IFN domain via a protease-cleavable linker, functionally unmasking the IFN when cleaved, and that the IFN domain is fused to the N-terminal of the Fc domain via a second linker [see claims 1 and 6]. Fu et al. demonstrates the activity of the prodrug using purified human IFNaR1 or IFNaR2 extracellular domains in combination with a human IFNa2-Fc [see specification, p.45, par. 2], and although Fu et al. does not explicitly disclose the IFNa2 subtype, the most well-known and commercialized are IFNa2a and IFNa2b, which differ from one another by a single amino acid at residue 23 but utilize the same IFNaR signaling pathway [see Paul et al., p. 2, par. 4]. As such, it would have been reasonably understood that Fu et al. utilized either hIFNa2b or hIFNa2a (instant claim 27). The human IFNaR1 extracellular domain necessarily comprises SD1-SD4 and the IFNR2 extracellular domain necessarily comprises D1 and D2, implicitly requiring the natural human sequences encoding their structures (instant claims 30 and 31). Fu et al. teaches that the prodrug may contain two copies of the IFN domain and further teaches that heterodimeric constructs may contain two or even four different type I interferons and specifically describes an FcA-FcB heterodimer in which a blocking receptor and an interferon may be fused to each of FcA or FcB [see p.12, par. 1] (instant claim 26). Nucleic acid constructs encoding the prodrug [see claim 11] (instant claim 62), recombinant cells engineered to express the prodrug [see claim 21] (instant claim 63), and methods of recovering the prodrug from procaryotic or eucaryotic expression system are disclosed [see p.24, par. 2] (instant claim 64). The prodrug may be formulated and administered with a pharmaceutically acceptable excipient [see p.25, par. 3] (instant claim 65) as a treatment for cancer [see claim 25] (instant claim 66) and can be delivered via any conventional route [see p.26, par. 4] (instant claim 73), including local administration, wherein the linker is selectively cleavable by a protease overexpressed in the tumor microenvironment (instant claims 67 and 68) to reduce systemic toxicity [see p.7 par. 2] (instant claim 69). Finally, Fu et al. notes the potential use of the prodrug in combination with additional advanced interferon therapy formats, such as antibody-cytokine bispecific fusion proteins [see p.8, par. 1] (instant claim 72).
It would have been obvious to one of ordinary skill in the art to modify the prodrug of Fu et al. to include both IFNaR1 and IFNaR2 in the same polypeptide chain with an IFN moiety as Smith et al. teaches that IFNaR1 and IFNaR2-derived components may be combined into the same polypeptide while maintaining activity, Fu et al. similarly teaches that both components mask IFN, and it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art to be useful [see In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). This composition would constitute a monovalent construct as each component has a single copy present (instant claims 74 and 75). Accordingly, there would have been a reasonable expectation of success that both receptor moieties would be incorporated into a single polypeptide chain and retain their interactions as this modification would have constituted combining known elements for their known use through known and routine techniques in the art of fusion proteins.
Regarding claim 26, as discussed above, Fu et al. teaches multivalent constructs distributed across Fc-associated polypeptides. As such, it would have been obvious to generate a bivalent construct comprising an additional masked IFN moiety comprising an IFNaR1 and IFNaR2 as Fu et al. teaches receptor masked interferons on different polypeptide chains of an Fc-associated multimeric construct (instant claim 26). One would have been motivated to do so to increase the immune responses at the target site.
Therefore, claims 1, 26, 27, 30, 31, 62-69, 72, and 73 are rejected on the ground of nonstatutory double patenting.
Claims 1, 28, and 29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claim 4 of U.S. Patent No. US7732167B2, in view of Fu et al., and in further view of Paul et al. and Thomas et al.
US7732167B2 teaches a fusion protein consisting of R2, R1, and F, in the N to C-terminus direction, wherein R2 consists of amino acids 35-233 of SEQ ID NO: 4, R1 consists of amino acids 28-335 of SEQ ID NO: 2, and F consists of an immunoglobulin-derived domain selected from the group consisting of an Fc domain of IgG and a heavy chain of IgG. The claimed portions of SEQ ID NOs: 4 and 2 correspond to the extracellular domains of IFNaR2 and IFNaR1 respectively [as evidenced by US7732167B2, specification, col. 7, par. 1]. US7732167B2 teaches a nucleic acid encoding the fusion protein, a host cell comprising the fusion protein, and a method of making the fusion protein comprising culturing host cells to express the protein and then recovering the protein from the cells [see claim 5].
US7732167B2 does not teach or suggest incorporating an IFN moiety into the construct or including additional mutations into the IFN moiety.
Fu et al. discloses a human interferon prodrug comprising an IFNaR domain, which may be either IFNaR1 or IFNaR2 [see claims 8 and 9], one or more Type 1 interferon (IFN) domains [see claims 1 and 4], which may be IFN-a, IFN-β, IFN-K, IFN-δ, IFN- ε, IFN-τ, IFN-ω or IFN-ζ [see claim 10], that retains interferon activity when not engaged by the IFNaR domain [see claim 1], and an Ig Fc domain [see claim 1] (instant claim 1). The Fc domain may be an IgG [see claim 2], which inherently discloses a dimeric Fc structure comprising a first polypeptide chain comprising an Fc domain and a second polypeptide chain comprising a second Fc domain associated with the first as an Fc domain requires two polypeptide chains, and additionally, Fu et al. teaches that Fc domains are useful because of their ability to dimerize and generate constructs comprising up to four interferons [see p. 12, par. 1] (instant claim 1). Fu et al. discloses that the INFaR domain is fused to the N-terminal of the IFN domain via a protease-cleavable linker, functionally unmasking the IFN when cleaved, and that the IFN domain is fused to the N-terminal of the Fc domain via a second linker [see claims 1 and 6]. Fu et al. demonstrates the activity of the prodrug using purified human IFNaR1 or IFNaR2 extracellular domains in combination with a human IFNa2-Fc [see specification, p.45, par. 2], and although Fu et al. does not explicitly disclose the IFNa2 subtype, the most well-known and commercialized are IFNa2a and IFNa2b, which differ from one another by a single amino acid at residue 23 but utilize the same IFNaR signaling pathway [see Paul et al., p. 2, par. 4]. As such, it would have been reasonably understood that Fu et al. utilized either hIFNa2b or hIFNa2a.
Thomas et al. discloses how different IFN subtypes bind differently to IFNaR1 and IFNaR2, specifically disclosing key point mutations to IFNa2 including L26A, L30A, and R149A, that contribute to receptor interaction [see p. 627, Probing Differential IFN Signaling with Structure-Based Mutational Analysis] (instant claims 28 and 29). Thomas et al. teaches that the L26A and L30A are within a hydrophobic interaction cluster at the binding interface with IFN that is common to both IFNa2a and IFNa2b [see p. 652, col. 1, par. 1, lines 27-32] and also teaches that R149A is conserved across all IFN subtypes except IFNw [see p. 652, col. 1, par. 2].
It would have been obvious to one of ordinary skill in the art to modify the prodrug of Fu et al. to include both IFNaR1 and IFNaR2 in the same polypeptide chain with an IFN moiety as Smith et al. teaches that IFNaR1 and IFNaR2-derived components may be combined into the same polypeptide while maintaining activity, Fu et al. similarly teaches that both components mask IFN, and it is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose. The idea of combining them flows logically from their having been individually taught in the prior art to be useful [see In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). Furthermore, this modification would have constituted a predictable variation, combining known elements for their known use through known and routine techniques in the art of fusion proteins. Accordingly, there would have been a reasonable expectation of success that both receptor moieties would be incorporated into a single polypeptide chain and retain their interactions.
Furthermore, it would have been obvious to combine these teachings and introduce the point mutations disclosed by Thomas et al. into the modified prodrug of Fu et al. to modulate the masking strength of the IFNaRs as Thomas et al. teaches that introducing these mutations into IFNa2 modifies receptor binding strength, Fu et al. teaches the functional masking of IFNa2, and Fu et al. further teaches unmasking at target sites. There would have been a reasonable expectation of success as Thomas et al. teaches that the mutations are within a region common to both IFNa2a and IFNa2b, both subtypes bind the same target, and the methods of inducing the relevant mutations are well known and routine in the art.
Therefore, claims 1, 28, and 29 are rejected on the ground of nonstatutory double patenting.
Response to Arguments
Applicant’s arguments regarding the prior art rejections have been fully considered and found persuasive. The rejections are withdrawn. However, it is noted that applicant’s argument regarding unexpected results has been considered but is not persuasive. Fig. 17 demonstrates that the construct having IFNaR1, IFN, and IFNaR2 moieties on the same polypeptide exhibits greater attenuation of ISRE-luciferase activity than the tested singly masked and split chain constructs but applicant has not established that the degree of increased attenuation itself would have been unexpected to a person having ordinary skill in the art in view of the closest prior art. More specifically, Smith et al. demonstrates substantial inhibition of biological activity in ISRE-luciferase assay with an IC50 of 1×10−10 M [see col. 8, par. 4], and as such, the claimed unexpected IFN masking results associated with the claimed architecture is consistent with the effects that the prior art would have led one to expect. Clearly put, the art recognized that compositions comprising IFNaR1 and IFNaR2 on the same polypeptide chain produce substantial IFN inhibition, and placing the IFN on the same polypeptide chain would be expected to also produce potent inhibition of said IFN.
Conclusion
No claims are allowed.
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/TIRONE D. JOHNSON/Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675
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