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 .
Claims Status
Claims 1-58 are pending and are examined on the merits.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code at Pg. 372, line 10. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Objections
Claim 58 is objected to for containing an apparent typo. The term “isolectric” recited in claim 58 should instead read “isoelectric”.
Appropriate correction is required.
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 1-14, 16-17, 20-23, 25-28, 33-36, 41-43, 45, 47-48, 50-51, and 53 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 1, 4, 7, 11, 17, 21, are indefinite for requiring CDR sequences (CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, CDR-L3) without specifying the particular sequences associated with each CDR or the method by which they are meant to be determined (e.g. Chothia, Kabat, IGMT, etc.). The recited SEQ ID NOs in the claims correspond to variable heavy and light chain sequences, and it is unclear which subsequences thereof are intended to correspond to which CDR. Although the disclosure specifies that “Determination of CDR regions is defined in Example 1”, Example 1 relates to a propriety “Pfabat” numbering algorithm unknown to one of ordinary skill in the art. As such, it is unclear what is intended to be encompassed by the claimed CDR sequences or how one is to determine the metes and bounds for each CDR-H1, CDR-H2, CDR-H3, CDR-L1, CDR-L2, and CDR-L3.
In addition, each of Claims 2-3, 5-6, 8-10, 12-14, 16, 20, 22-23, 25-28, 33-36, 41-43, 45, 47-48, 50-51, and 53 depend from or incorporate all of the limitations of one of Claims 1, 4, 7, 11, 17, or 21 but fail to further specify the CDR sequences, and are therefore rejected for the same reasons set forth above.
Improper Markush
Claims 3, 6, 13, 20, 25-26, 28 rejected on the basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush groupings of 3, 6, 13, 20, 25-26, and 28 are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons:
Each of claims 3, 6, 13, 20, 25-26, and 28 are drawn to a variety of alternative antibody properties including, viscosity of a particular formulation, IC50 in neutralization assays, species cross-reactivity, binding KD, half-life, melting temperature, and particular amino acid substitutions. Each of these properties reads broadly on a discrete categories of antibody structure and function such as protein stability (e.g. melting temperature), binding affinity (e.g. KD), binding specificity (e.g. cross reactivity), pharmacodynamics (e.g. IC50), pharmacokinetics (serum half-life), and structural modification (amino acid substitution) – and therefore the alternatives presented in the claims share neither a single structural similarity or common use.
By way of example (and not comprehensive of all properties lacking similarity in the claimed Markush groups), the skilled artisan would not recognize the following as reasonable alternatives:
Claim 20: formulation viscosity, binding affinity to its antigen, or half-life in cynomolgus monkey
Claim 25: cynomolgous cross reactivity, IC50 for neutralization of IL-4 induction of CD23, or a lysine residue 93 in the light chain
Claim 3: cynomolgus cross-reactivity, viscosity of a particular formulation, or a lysine at residue 93 in the light chain
Claim 6: IC50 of less than 100pM in a IL-13 neutralization assay, terminal half-life of at least 18 days in TG32 mice, or non-reactivity with dog, rabbit, or mouse antigen
Claim 13: melting temperature of 68°C, IC50 of less than 15 pM in a human TSLP neutralization assay, a score of less than 2% high molecular mass species as determined by aSEC
Claim 26: KD with human IL-13, half-life in cynomolgus monkey, or non-reactivity with dog, rabbit, or mouse IL-13
Claim 28: binding affinity of less than 1 pM, viscosity of a particular formulation, or cross-reactivity with cynomolgus IL-33
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 20, 25-26, and 28 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. This is a written description rejection.
Scope of the claimed genus
Claim 20 is drawn to an antibody having particular activity towards IL-4, IL-13, IL-12 and IL-23. However, Claim 20 depends from Claim 17, which specifies sequences of the p40 (IL12/IL23) binding domain, but not those of the IL-4 or IL-13 binders.
Similarly, Claims 25-26 and 28 depend indirectly from Claim 21, which specifies sequences of the IL-33 binding domain, but not those of the IL-4 or IL-13 binders. However, Claims 25-26 and 28 recite particular affinities, cross-reactivity, IC50, and half-lives of IL-4 and IL-13 binding domains.
Accordingly, each of Claims 20, 25-26, and 28 are drawn to IL-4 and/or IL-13 with unspecified structure or sequences limited only by a set of desired functional qualities. The resulting scope of the claims is massive, encompassing an enormous number of potential IL-4 or IL-13 binding domains provided they satisfy just one of the variety of functional limitations set forth in the claims.
State of the prior art
IL-13 and IL-4 binding domains are known in the art and have been previously used as part of bispecific antibodies. For example, Spiess et al. 2013 (Journal of Biological Chemistry, 288(37), 26583-26593.; IDS dated 11/08/2024) teaches neutralizing bispecific antibodies with two antigen binding domains independently targeting IL-13 and IL-4 (Abstract). The IL-13 binder of Spiess is derived from lebrikizumab, which “binds soluble human IL-13 with a Biacore-derived KD lower than the detection limit, 10pM” (Pg. 26586, § Results, ¶1), and which maintains a KD less than 60 pM when part of a bispecific antibody (Table 3). However, the sequence of lebrikizumab shares almost no similarity to that of the IL-13 binding domains of the instant claims (see DrugBank ID: DB11914; “Lebrikizumab”; PTO-892), and the skilled artisan would be unable to predict the properties of any particular antibody given its structure or envisage the structure of an antibody provided only with desired binding characteristics.
As was well known in the antibody art, the formation of an intact antigen binding site in a conventional antibody typically requires the association of the complete heavy and light chain variable regions of a given antibody, each of which comprises three CDRs (or hypervariable regions) which provide the majority of the contact residues for the binding of the antibody to its target epitope (reviewed in Sela-Culang et al. Frontiers in Immunology 4 (2013): 302.; PTO-892). It is generally understood that all six CDRs in combination and in a specific order (HCDR1, HCDR2, HCDR3, LCDR1, LCDR2, LCDR3) are required to convey an antibody’s specificity to its target, and that neither the CDRs themselves nor individual VH and VL domains are interchangeable.
Sela-Culang further teaches that antigens lack intrinsic properties that clearly differentiate between epitopic and non-epitopic residues, and any part of the antigen surface my become part of an epitope under some circumstances (“Ab Epitope Prediction”; Pg. 2). In the same vein, Edwards et al. 2003 (Journal of molecular biology 334.1 (2003): 103-118.; PTO-892) endeavored to uncover the breadth of the structural diversity of antibodies a single antigen can give rise to.
Edwards employed a phage display library to screen for antibodies that bind a single protein, BLyS, and isolated over 1000 unique anti-BLyS antibodies, each comprising a different amino acid sequence (Abstract). These antibodies were structurally diverse, resulted from nearly all possible Vh, D, and Jh, germlines (Pg. 105; “Vh and Vl germline usage”), and comprised 568 distinct Vh CDR3 sequences, ranging in length from 5 to 25 amino acid residues (Fig. 4; “Vh CDR3 sequence diversity”; Pg. 105). Together, these works highlight that neither knowledge of the antigen sequence nor the antibody sequence is necessarily predictive of its function.
Further, the skilled artisan has long recognized that even minor changes in the amino acid sequences of the VH and VL, particularly in the CDRs, may dramatically affect antigen-binding function, as evidenced by Rudikoff 1982 (Proceedings of the National Academy of Sciences 79.6 (1982): 1979-1983.; PTO-892). Rudikoff teaches that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function (Abstract).
Although more recent advances in computational modelling of CDRs have led to improvements in rational mutagenesis of antibodies, the overall effects of any given mutation on antibody function remain unpredictable. For example, Chiu et al. 2019 (Antibodies, 8(4), 55.; PTO-892) teaches that although modeling has proven accurate for framework region sequences, CDR modeling requires further development and improvement (Pg. 6, ¶2). In particular, prediction of the structure of HCDR3 could not be accurately produced when given the Fv structures without their CDR-H3s (Pg. 6, ¶2). Chiu further states “despite the obvious development in algorithms and computer power, the quality of antibody structure prediction, particularly regarding CDR-H3, remains inadequate” (Pg. 11, ¶ 2).
Chiu further discusses the state of the art as it relates to antibody humanization and highlights the importance of VH-VL pairing to antigen-binding affinity (§2.1.3). For example, even in cases where structural analysis indicated that all the interactions between the antibody CDRs and the antigen were conserved, changes in the relative orientation of the VH and VL domains can cause a dramatic loss in antibody affinity – and a modification as small as a single back-mutation in the framework region has the potential capacity to completely restore this diminished affinity (Pg. 14, ¶3). Chiu further teaches the utility of back-mutations more generally, as “straightforward CDR grafting may result in reduced target binding even if the VH-VL interface residues are preserved” (Pg. 16, §2.1.4), and back-mutations in the framework region can both modulate binding affinity and improve antibody expression. However, although some residues are frequently targeted for back mutation – such as those in the vernier zone known to influence the structure of CDRH2 – the importance of these residues depends largely on the particular CDRs of the grafted binding domain, and it is “not always the case” that such mutations will be of benefit to the antigen-binding affinity/function.
Finally, Herold et al. 2017 (Scientific reports, 7(1), 12276.; PTO-892), hereinafter “Herold”, teaches that it should be emphasized that there is no correlation between experimentally determined change in antibody binding affinity and a given mutation and additionally that no such correlation is expected because antigen binding is “affected by each CDR loop differently” and changes thereto “can in principle affect antigen binding affinity in an unpredictable way” (Pg. 14, ¶2). Further, Herold asserts that multiple determinants regulate antigen affinity and the interactions with CDRs are complex (Pg. 14, ¶3). Herold further teaches that variable heavy chain (VH) mutations led to a decrease in binding affinity, with as much as 20-fold higher KD in the mutant versus wild type (Pg. 4, ¶3), and summarizes the antigen binding KD differences based on point mutations in the VH or VL of an IgG antibody (Pg. 6, Table 1).
Description of representative species in the specification
MPEP § 2163 states that 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.
Examples 3-12 highlight the development of humanized anti-IL-4 (Examples 3-7) and anti-IL-13 (Examples 8-12) antibodies with improved potency relative to the starting parent antibodies. However, each of these species shares a high amount of sequence identity. In view of the enormous breadth of the potential antibody repertoire highlighted by Edwards above, the skilled artisan would not reasonably consider disclosure of the relatively small number of antibodies characterized in the instant specification representative of the claimed genus.
Identifying characteristics and structure/function correlation
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied 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 claimed genus. To meet this requirement in the instant case, the specification must describe structural features that the skilled artisan as of the effective filing date would have expected to convey the claimed binding activity.
The disclosure details the cross reactivity, half-life, IC50, etc. of individual species of the invention (e.g. “IL13433-1258”, Examples 72-77; “IL413TSLP-1024”, Examples 78-84. In addition, the disclosure highlights affinity optimization and the impact of the introduced changes on the antibody-antigen structure for IL-4 binding domain 1285 (Example 13) and IL-13 binding domain 1307 (Example 14). However, there is no direction provided on how to identify antibodies having the instantly claimed activity outside of those having same structure/sequence as instantly disclosed. Accordingly, one of ordinary skill in the art would be unable to envisage anti-IL-13 or anti-IL-4 commensurate in scope with the claims.
Claim Rejections - 35 USC § 102
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.
Claims 29 and 44 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wu et al. 2018 (Protein Engineering, Design and Selection, 31(7-8), 249-256.; IDS dated 11/08/2024), herein “Wu”.
Wu teaches trispecific antibodies having the same structure as instantly claimed – namely, 5 polypeptide chains wherein a first chain has an antibody VL/CL fused N terminal to a VH-CH1-CH2-CH3, a second chain comprising a VH-CH1-CH3-CH3, a third chain comprising VH-CH1 domains that pair with the N-terminal VL-CL domains of the first chain, a fourth chain comprising a VL-CL that pairs with the VH-CH1 of the first chain, and a fifth chain comprising a VL-CL that pairs with the VH-CH1 of the second chain (Fig. 1, format “N_L”; copied below).
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Regarding Claim 44, Wu teaches the antibodies were prepared in a solution with PBS (Pg. 250, § Purification and biochemical characterization), which satisfies the broadest reasonable interpretation of a “pharmaceutical composition” in a “pharmaceutically acceptable carrier” (see instant specification pg. 215, ¶1-2)
Claims 32 is rejected under 35 U.S.C. 102(a)(1) as being anticipated by Bennett et al. 2015 (WO 2015/173756 A2; IDS dated 11/08/2024), herein “Bennett”.
Bennett teaches modified Fc domains for bispecific antibodies having a first chain comprising the mutations D232R and K440R paired with a second chain comprising the mutations D232E and L391E (Pg. 128, lines 19-21).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 31 is rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. 2018 (Protein Engineering, Design and Selection, 31(7-8), 249-256.; IDS dated 11/08/2024), herein “Wu”, as applied to claim 29 above, and further in view of Bennett et al. 2015 (WO 2015/173756 A2; IDS dated 11/08/2024), herein “Bennett”.
The teachings of Wu are summarized above.
In addition, Wu teaches that the trispecific antibody further comprise modifications to the Fc domains to promote heterodimerization (Pg. 252, § Results, ¶1).
Wu does not teach the particular Fc mutations comprised within instantly claimed SEQ ID NOs: 147 and 148.
This deficiency is cured by Bennett.
Bennet teaches Fc mutations that promote heterodimer formation of a multispecific antibody comprising identical paired sequences to instant SEQ ID NOs: 147 and 148 (Table 26; Pg. 128, “Method 2 (M2)”; Bennett SEQ ID NOs: 49 and 48; alignment below)
SEQ ID NO: 147 (SEQ147)/Bennet SEQ ID NO: 49 (BEN49)
SEQ147 1 QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
BEN49 2 QPREPQVYTLPPSREEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD 61
SEQ147 61 GSFFLYSRLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 106
||||||||||||||||||||||||||||||||||||||||||||||
BEN49 62 GSFFLYSRLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 107
SEQ ID NO: 148 (SEQ148)/Bennet SEQ ID NO: 48 (BEN48)
SEQ148 1 QPREPQVYTLPPSREEMTKNQVSLTCEVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
BEN48 2 QPREPQVYTLPPSREEMTKNQVSLTCEVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSD 61
SEQ148 61 GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 106
||||||||||||||||||||||||||||||||||||||||||||||
BEN48 62 GSFFLYSKLTVDKSRWQQGNVFSCSVMHEALHNHYTQKSLSLSPGK 107
Bennett teaches that multispecific antibodies comprising said paired Fc sequences (e.g. “C5xAv3-M2”) display only 4.6% mispairing (Pg. 129, Example 27).
It would have been obvious to one of ordinary skill in the art to substitute the Fc domains of Wu with those taught by Bennett to arrive at a trispecific antibody comprising instant SEQ ID NOs: 147 and 148 because doing so would constitute a simple substitution of one known element for another to obtain predictable results. See MPEP 2143(I). In the present instance, each of the modified Fc domains satisfy the same purpose of promoting heterodimeric antibody formation. The skilled artisan would have had a reasonable expectation of success because Bennett teaches that bispecific antibodies comprising paired Fc regions identical to instantly claimed SEQ ID NOs: 147 and 148 display minimal undesired mispairing.
Claim 30 is rejected under 35 U.S.C. 103 as being unpatentable over Wu et al. 2018 (Protein Engineering, Design and Selection, 31(7-8), 249-256.; IDS dated 11/08/2024), herein “Wu”, and Bennett et al. 2015 (WO 2015/173756 A2; IDS dated 11/08/2024), herein “Bennett” as applied to claims 29 and 31 above, and further in view of Strop et al. 2012 (Journal of molecular biology, 420(3), 204-219.; IDS dated 11/08/2024).
The teachings of Wu and Bennett are summarized above.
Wu and Bennett do not teach a pair of hinge sequence according to instant SEQ ID NO: 129 and 131. This deficiency is cured by Strop.
SEQ ID NO NOs: 129 and 130 correspond to an IgG1 hinge sequence containing a D221E or D221R substitution relative to the wild type hinge sequence respectively (annotated below; WT hIgG1 hinge referenced from Strop Fig. 1b):
WT IgG1 Hinge 216 EPKSCDKTHTCPPCP 230
SEQ ID NO: 129 216 EPKSCEKTHTCPPCP 230
SEQ ID NO: 131 216 EPKSCRKTHTCPPCP 230
Strop teaches mutations that promote heterodimerization of two different Fab arms whereby charged mutations of the hinge region, such as 221E paired with 221R, not only facilitates half-monomer exchange but also stabilizes heterodimers (Abstract; Pg. 206, § Generation of bispecific antibodies).
Strop teaches that the hinge mutations when combined with charge-pair mutations in the CH3 domain enables Fab arm exchange at reducing conditions mild enough that light chains remain paired with their original heavy chains, thus eliminating the need for a common light chain.
It would have been obvious to one of ordinary skill in the art to further modify the hinge regions of the paired Fab arms according to the combined teachings of Wu and Bennett to include a charge-pair mutation such as D221E/R, resulting in a hinge having the sequence of instant SEQ ID NO: 129 and 131, respectively. The skilled artisan would have been motivated to include this hinge mutation because Strop teaches that such a mutation allows for Fab arm exchange under mild conditions that preserve the original light chain association. There would have been a reasonable expectation of success because Strop teaches that the charged hinge mutations promote Fab arm exchange and stabilize the resulting heterodimeric antibodies.
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 54-57 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 22-25 of copending Application No. 18/314,339 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding instant Claim 54, ‘339 claim 23 is drawn in part to an isolated polynucleotide comprising SEQ ID NO: 237, which encodes an anti-p40 light chain and is identical to instantly claimed SEQ ID NO: 195 of Claim 54 xix (alignment below).
SEQ195 1 GACATCCAGATGACCCAGTCTCCATCCTCACTGTCTGCATCTGTGGGAGACAGAGTCACC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
339-237 1 GACATCCAGATGACCCAGTCTCCATCCTCACTGTCTGCATCTGTGGGAGACAGAGTCACC 60
SEQ195 61 ATCACTTGTCGGGCCAGTCAGGGTATTAGCAGCTGGCTGGCCTGGTATCAGCAGAAACCA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
339-237 61 ATCACTTGTCGGGCCAGTCAGGGTATTAGCAGCTGGCTGGCCTGGTATCAGCAGAAACCA 120
SEQ195 121 GAGAAAGCCCCTAAGTCCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCCCATCA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
339-237 121 GAGAAAGCCCCTAAGTCCCTGATCTATGCTGCATCCAGTTTGCAAAGTGGGGTCCCATCA 180
SEQ195 181 AGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
339-237 181 AGGTTCAGCGGCAGTGGATCTGGGACAGATTTCACTCTCACCATCAGCAGCCTGCAGCCT 240
SEQ195 241 GAAGATTTTGCAACTTATTACTGCCAACAGTATAATATTTATCCCTACACCTTCGGACAA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
339-237 241 GAAGATTTTGCAACTTATTACTGCCAACAGTATAATATTTATCCCTACACCTTCGGACAA 300
SEQ195 301 GGTACAAAACTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCA 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
339-237 301 GGTACAAAACTGGAGATCAAACGAACTGTGGCTGCACCATCTGTCTTCATCTTCCCGCCA 360
SEQ195 361 TCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTAT 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
339-237 361 TCTGATGAGCAGTTGAAATCTGGAACTGCCTCTGTTGTGTGCCTGCTGAATAACTTCTAT 420
SEQ195 421 CCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
339-237 421 CCCAGAGAGGCCAAAGTACAGTGGAAGGTGGATAACGCCCTCCAATCGGGTAACTCCCAG 480
SEQ195 481 GAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACG 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
339-237 481 GAGAGTGTCACAGAGCAGGACAGCAAGGACAGCACCTACAGCCTCAGCAGCACCCTGACG 540
SEQ195 541 CTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGC 600
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339-237 541 CTGAGCAAAGCAGACTACGAGAAACACAAAGTCTACGCCTGCGAAGTCACCCATCAGGGC 600
SEQ195 601 CTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 642
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339-237 601 CTGAGCTCGCCCGTCACAAAGAGCTTCAACAGGGGAGAGTGT 642
Regarding instant Claims 55-57, ‘339 claims 24-26 are drawn to vectors, host cells, and a method of producing antibody comprising culturing the host cell. Although ‘339 claims 24-26 depend from ‘339 claim 22, which recites the p40-VL polynucleotide sequence rather than the full p40-LC sequence of ‘339 claim 23 and instant Claim 54-57, it would have been obvious to one of ordinary skill in the art that the claims of ‘339 could further encompass vectors, host cells, and methods of producing an antibody comprising the full p40 light chain sequence of SEQ ID NO: 195/237, in part because production of a full intact antibody requires a complete light chain sequence.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Claims 15, 18-19, 24, 37-40, 46, 49, and 52 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
The following is a statement of reasons for the indication of allowable subject matter: CDR sequences corresponding to the instantly claimed IL-4, IL-33, and IL-13, and TSLP binding domains are free of the prior art of record.
The nearest prior art is considered to be Giles-Komar et al. 2005 (US 6,902,734 B2; ...) which teaches the anti-p40 VH/VL sequences of, for example, instant Claim 17 (see ‘734 claim 1; SEQ ID NOS:7-8). However, ‘734 neither teaches nor suggests trispecific molecules further comprising IL-4 and IL-13 binding domains.
Conclusion
No claim is allowed.
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/BRYAN WILLIAM HECK/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643