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 .
Priority
This application is a CON of International Application No. PCT/US2021/047574, filed on 08/25/2021, which claims domestic benefit to US provision application 63/070,782, filed 08/26/2020.
Claim Status
The Amendment, filed on 06/08/2023, is acknowledged in which:
Claims 1-45 are canceled.
Claims 46-69 are new.
Claims 46-69 are pending in the instant application and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 6/18/2024 has been considered by the examiner.
Drawings
The drawings are objected to because: FIG. 1 does not include a figure legend matching the clones tested with data points graphed. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
The drawings are objected to as failing to comply with 37 CFR 1.84(p)(5) because they include the following reference character(s) not mentioned in the description: 9D9-1C1, 16F2-2F3 and 16G3-1E5 (FIG. 1). Corrected drawing sheets in compliance with 37 CFR 1.121(d), or amendment to the specification to add the reference character(s) in the description in compliance with 37 CFR 1.121(b) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The disclosure is objected to because of the following informalities:
“glyco proteins” should read “glycoproteins” (¶ [00170], line 2)
“immuoglobulin" should read “immunoglobulin” (¶ [00205], line 2)
“greata” should read “areata” (¶ [00337], line 2)
“cicatrical” should read “cicatricial” (¶ [00337], line 7)
“erthematosus" should read “erythematosus” (¶ [00337, line 10)
“polychrondritis” should read “polychondritis” (¶ [00337], pg 91, line 1)
“Raynauld’s” should read “Raynaud’s” (¶ [00337], pg 91, line 3)
“takayasu" should be capitalized (¶ [00337], pg 91, line 5)
“arteristis” should read “arteritis” (¶ [00337], pg 91, line 5)
“encephilitis" should read “encephalitis” (¶ [00338], line 2)
“mABs” should read “mAbs” (¶ [00352], last line)
Appropriate correction is required.
The use of the terms “azymetric” (¶ [00217], pg 58, line 4), “CytoFLEX” (¶ [00351], line 7), “Biacore” (pg 94, Example 6 title; ¶ [00355], line 3; pg 94, Table 19 title), which are trade names or marks used in commerce, has been noted in this application. Each term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Rejections - 35 USC § 112(b)
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.
Claim 55 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.
The claim is drawn to modifications to the Fc domain to facilitate greater ratio of heteromultimer to homomultimer forms, however, the claim further recites this ratio is “relative to a non-engineered interface” which introduces ambiguity to the claim as a non-engineered interface would only have homomultimer forms. Thus it is unclear if the modifications would generally allow heteromultimer formation (i.e. relative to non-engineered state) or if the modification would facilitate a higher amount of heteromultimers in comparison to homomultimers (i.e. relative to each form). To overcome this rejection examiner recommends removing “relative to a non-engineered interface” from the claim.
Claim Rejections - 35 USC § 112(d)
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 47, 48, and 51 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.
Regarding claims 47 and 48, the instant claims are dependent on claim 46 which claims specific pairing of CDR sequences (sets of 6). The base claim recites a VL comprising LCDR3 of SEQ ID NO:86 is only paired with a VH comprising HCDR2 of SEQ ID NO:7399 (limitation (b)), however dependent claims 47 and 48 recite a VH comprising SEQ ID NOs: 1 or 2, which comprise identical sequences comprising an HCDR2 with 100% identity to SEQ ID NO: 21 (see alignment below) paired with VL comprising LCDR3 SEQ ID NO:86 (SEQ ID NOs: 13 and 14). Therefore these claims are improperly dependent for failing to include all the limitations of the base claim.
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253
712
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Regarding claim 51, the instant claim, also dependent on claim 46 which claims specific NKp30 antibody molecules comprising full sets of 6 CDRs, recites species that have less than 6 CDRs (e.g. sdAbs and camelid), and therefore is improperly dependent on the base claim.
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 § 112(a)
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 46-48 and 51-69 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.
Claim 46 is drawn to an antibody molecule that binds to NKp30, comprising CDRs with amino acid sequence selected from:
(a)(i) HCDRs SEQ ID NOs: 19, 21, and 23; and (ii) LCDRs SEQ ID NOs: 26, 28, and one of 30, 7395 or 113; or
(b)(i) HCDRs SEQ ID NOs: 19, 7399, and 23; and (ii) LCDRs SEQ ID NOs: 26, 28, and one of 30, 7395, 86, or 113.
This claim encompass a genus of antibody formulations which suggests interchangeability of 2 possible HCDR2 sequences with 3 or 4 possible LCDR3 sequences. Claims 47 and 48, dependent on claim 46, recite VH sequences comprising HCDR SEQ ID NOs: 19, 21, and 23 paired with VL sequences comprising LCDR SEQ ID NOs: 26, 28, and any one of 30, 7395, 86 or 113 and with at least 80% (claim 47) or 100% identity (claim 48) to sequences recited (i.e. framework variability).
Claim 51, dependent on claim 46, recites the antibody molecule wherein the antibody molecule is a full antibody or an antigen-binding fragment thereof, a bivalent antibody, or a bispecific antibody, wherein the antigen-binding fragment is a Fab, F(ab’)2, an single chain Fv, a single domain antibody (sdAb), a diabody, or a camelid antibody.
MPEP 2163.I1.A.3.a.ii. states that the written description requirement for claimed genus may be satisfied through a sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus.
The instant specification discloses 10 antibody species (Table 19; Figures 1 and 2) each comprising full set of 6 CDRs with evidence of NKp30 binding and sufficient written description (summarized in the table below).
SEQ ID NOs
Construct
scFv
CDRs
BJM1078
7310
19-21-23-26-28-86
BJM1079
7311
19-21-23-26-28-86
BKM0138
17
19-21-23-26-28-30
BKM0139
7386
19-21-23-26-28-7395
BKM0140
7387
19-21-23-26-28-7395
BKM0141
7388
19-21-23-26-28-30
BKM0142
7389
19-7399-23-26-28-86
BKM0143
7390
19-7399-23-26-28-86
BKM0144
7391
19-7399-23-26-28-113
BKM0145
7392
19-7399-23-26-28-113
However, guidance for arriving at additional variations encompassed by the genus of anti-NKp30 antibodies as currently claimed is not sufficient to allow one of ordinary skill in the art to envision all recited CDR combinations within claimed genus that predictably retain NKp30 binding (i.e. claimed antibodies (shown in alignment below) with HCDR2 SEQ ID NO:7399 paired with LCDR3 SEQ ID NOs: 30 or 7395 lack sufficient written description or embodiments with less than 6 CDRs (e.g. sdAbs or camelid antibodies)).
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895
849
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The state of the art near the effective filing date of the claimed invention demonstrates that antibody functionality is dependent on amino acid structure, particularly regarding complementarity of the CDR domains. It is understood by one of ordinary skill in the art that mutations to CDRs is unpredictable and that each construct requires function testing.
Rabia (Rabia LA et al. Understanding and overcoming trade-offs between antibody affinity, specificity, stability and solubility. Biochem Eng J. 2018 Sep 15;137:365-374.) teaches that antibody-antigen binding specificity is primarily mediated by the six CDRs within the sequences of variable heavy and variable light chains (Introduction, paragraph 1). Given the chemical diversity possible within combined CDRs alone (~20 different amino acids at ~60 sites), not all combinations can result in viable antibodies suitable for therapeutic applications. An outstanding challenge in the field is that optimizing antibodies based on antigen affinity can lead to defects in other properties such as stability, specificity, and solubility (page 366, column 1, ¶ 2). Even natural antibody maturation, which relies on random somatic mutations, is followed by clonal selection for antibodies with improved affinity and/or with mutations that compensate for destabilizing affinity enhancing mutations (page 366, column 2, paragraph 2). It is expected that most somatic mutations that increase affinity, such as those that increase hydrophobicity or charge, can also reduce specificity. Based on these teachings, introducing variation in antibody structure, particularly in the arrangement of CDR regions, requires thorough testing to ensure suitable binding specificity and antibody stability.
Herold (Herold EM, John C, Weber B, et al. Determinants of the assembly and function of antibody variable domains. Sci Rep. 2017;7(1):12276) teaches 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).
Regarding single domain antibodies (sdAbs) recombinantly-produced from heavy chain variable regions (i.e. sdAb with 3 CDRs instead of 6 CDRs), Wagner (Int J Mol Sci. 2018 Nov 2;19(11):3444) teaches that design of nanobody grafts with CDRs derived from conventional antibodies (VH CDRs) requires careful consideration because conventional antibodies utilize both VH and VL domains for antigenic recognition (page 2, last ¶). A direct CDR grafting approach was observed to produce weak antigen binders (abstract). A second step was required, in which additional affinity maturation steps by panning of synthetic phage libraries was performed generate nanobodies with sufficient antigen binding, resulting several changes in grafted CDR residues (Abstract; Figure 6B). Therefore, based on these teachings it would be unlikely that direct CDR grafting from conventional VH CDRs to a sdAb format without modifications (e.g. using only 3 CDRs from functional 6 CDR sets) would predictably generate a functional nanobody.
Therefore, making changes to the CDR sequences of an antibody is a highly unpredictable process and one skilled in the art could not a priori make any predications regarding residue variability in CDR domains with any reasonable expectation of success nor envisage the full breadth of CDR combinations as claimed that would still possess claimed NKp30 binding. Therefore, instant claims 46-48 and 51 and subsequent dependent claims 52-69 that do not resolve the issues discussed above were determined to not meet the written description requirement.
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.
US 12,384,842 B2
Claims 46-49, 51-57, 59-61, and 63-67 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-23 of U.S. Patent No. 12,384,842 B2 (herein US’842). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 46, claim 1 US’842 claims an NKp30 antibody comprising sequences identical to the instant claims (SEQ ID NO:7313 nested within instant SEQ ID NO:19; SEQ ID NOs: 6001, 7315, 7326, 7327, and 7329 are identical to instant SEQ ID NOs: 21, 23, 26, 28, and 86, respectively). It is further evident that the VH/VL as recited in subsequent dependent claims 2-7, includes residues that anticipate the full sequence of instantly claimed HCDR1 SEQ ID NO:19 (e.g. SEQ ID NO:7302 is identical to instant SEQ ID NOs:1 and 2 comprising instant CDRs - SEQ ID NOs: 19, 21, and 23).
Regarding claims 47-48 (dependent on claim 46), claims 2-7 of US’842 (dependent on claim 1) claim sequences identical to the instant claims (SEQ ID NO:7302 identical to instant SEQ ID NOs: 1 and 2; SEQ ID NO: 7309 and 7305 are identical to instant SEQ ID NOs: 13 and 14, respectively) and within 80% identity.
Regarding claim 49 (dependent on claim 46), claim 8 of US’842 (dependent on claim 2) claims antibody sequences SEQ ID NOs: 7310 or 7311, which have at least 80% sequence identity to instant SEQ ID NOs: 17 and 7386-7392 (see table below).
Instant (SEQ ID NOs)
% Identity
US’842 (SEQ ID NOs)
7310
7311
17
87.8
99.5
7386
87.8
99.5
7387
99.5
88.1
7388
99.5
88.1
7389
87.8
99.5
7390
99.5
88.1
7391
86.9
98.6
7392
98.6
87.2
Regarding claim 51-52 (dependent on claim 46), claim 9 of US’842 (dependent on claim 2) claims a multispecific molecule comprising the antibody or antigen-binding portion thereof.
Regarding claim 53-56 (dependent on claim 52), claim 13 of US’842 (dependent on claim 1) claim the antibody comprises an immunoglobin constant region that is further claimed as is an IgG1 comprising substitutions at positions selected from 347, 349, 350, 351, 366, 368, 370, 392, 394, 395, 397, 398, 399, 405, 407, 409, and any combination thereof (claim 14) that are defined to increase or decrease dimerization e.g. relative to a non-engineered interface by providing a paired cavity-protuberance, an electrostatic interaction, or a strand-exchange (column 17, lines 14-33). Claim 15 of US’842 further claims specific mutations of T366S, L368A, Y407V, T366W, and any combination thereof.
Regarding claims 57, 59-60, and 63 (dependent on claim 52), claim 10 of US’842 (dependent on claim 9) claims the multispecific molecule further comprises a (a) a tumor targeting moiety; (b) a cytokine molecule; (c) a T cell engager; (d) a stromal modifying moiety; or (e) any combination thereof.
Regarding claim 61 (dependent on claim 60), claim 11 of US’842 (dependent on claim 9) claims the multispecific molecule further comprises (a) a T cell engager that binds to an antigen present on an autoreactive T cell associated with inflammation or autoimmune disorder or (b) binds to an antigen present on the surface of a cell infected by a virus or bacteria.
Regarding claim 64 (dependent on claim 46), claim 16 of US’842 claims a polynucleotide encoding the antibody or antigen binding fragment of claim 2.
Regarding claim 65 (dependent on claim 46), claim 20 of US’842 claims a method of making the antibody or antigen binding portion of claim 2, comprising culturing a host cell (comprising the polynucleotide of claim 16 according to claim 17) under suitable conditions for gene expression and/or homo- or heterodimerization.
Regarding claim 66 (dependent on claim 46), claim 21 of US’842 claims a pharmaceutical composition comprising the antibody or antigen binding portion of claim 2; and a pharmaceutically acceptable carrier, excipient, or stabilizer.
Regarding claim 67 (dependent on claim 46), claim 22 of US’842 claims a method of treating a disease or condition (wherein the disease is cancer, an autoimmune or inflammatory disorder, or an infectious disorder - claim 23) comprising administering to a subject in need thereof the antibody or antigen binding portion of claim 2.
US 12,358,982 B2
Claims 46-49, 51-53, 57-58, and 60-62 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9-13 and 18-19 of U.S. Patent No. 12,358,982 B2 (herein US’982). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 46, 51-52, and 60-62, the instant claim is drawn to a composition comprising an antibody molecule that binds to NKp30, and use inclusive or open-ended language to define the scope of the claim. Specifically, the term “comprising” is inclusive and does not exclude additional, unrecited elements or method steps (see MPEP 2111.03) (i.e. additional antigen binding domains). Claim 9 of US’982 claims a multifunctional molecule with an antigen binding domain that selectively binds to T cell receptor beta chain constant domain 1 (TRBC1) (claim 1) with a second antigen binding domain with CDRs sharing 100% with instantly claimed CDRs (SEQ ID NO:7313 nested within instant SEQ ID NO:19; SEQ ID NOs: 6001, 7315, 7326, 7327, and 7329 are identical to instant SEQ ID NOs: 21, 23, 26, 28, and 86, respectively). It is further evident that the VH/VL as recited in subsequent claims 10 and 11, that additional residues are anticipated in the full sequence of instantly claimed HCDR1 SEQ ID NO:19 (e.g. SEQ ID NO:7302 is identical to instant SEQ ID NOs:1 and 2 comprising instant CDRs - SEQ ID NOs: 19, 21, and 23). In summary, the bispecific molecule disclosed anticipates a species of antibody molecule that binds to NKp30 with scope of the instantly claimed genus and is therefore patentably indistinct.
Regarding claims 47-48 (dependent on claim 46), Claims 10-12 of US’982 claims the multifunctional molecule described above (claim 1) with a second antigen binding domain with at least 75% identity to VH/VL sequences comprising 80-100% identity to instantly claimed VH/VL (e.g. SEQ ID NO:7302 identical to instant SEQ ID NOs: 1 and 2 (containing CDR SEQ ID NOs: 19, 21, and 23); SEQ ID NO: 7309 and 7305 are identical to instant SEQ ID NOs: 13 and 14, respectively (containing CDR SEQ ID NOs: 26, 28, and 86)).
Regarding claim 49 (dependent on claim 46), claim 13 of US’982 claims the multifunctional molecule of claim 1, wherein the second antigen binding domain comprises an amino acid sequence with at least 85% identity to SEQ ID NO:7383, which contains sequences within 80% identity to instantly claimed sequences (see table below).
Instant (SEQ ID NOs)
US’982 SEQ ID NO: 7383
(% identity)
17
99.5
7386
99.5
7387
88.1
7388
88.1
7389
99.5
7390
88.1
7391
98.6
7392
87.2
Regarding claims 53 and 57-58 (dependent on claim 52), claim 18 of US’982 claims the multifunctional molecule of claim 1 (TRBC1 antigen binding domain within claim 2) further comprising the VH/VL of claim 9 (patently indistinct as discussed above), and a cytokine molecule that is IL-2 (i.e. species with scope of the instantly claimed genus). Claim 19 of US’982 further claims the multifunctional molecule of claim 18 comprises an immunoglobin constant domain.
US 18/048,614
Claims 46-49, 52 and 60-62 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 133-136 and 145-146 of copending Application No. 18/048,614 (herein US’614). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 46, 51-52, and 60-62, the instant claim is drawn to a composition comprising an antibody molecule that binds to NKp30, and use inclusive or open-ended language to define the scope of the claim. Specifically, the term “comprising” is inclusive and does not exclude additional, unrecited elements or method steps (see MPEP 2111.03) (i.e. additional antigen binding domains). Claim 127 of US’614 claims a multifunctional molecule comprising a first antigen binding domain that binds to TCR beta chain constant domain (TRBC2) and a second antigen domain that binds to NKp30. Claim 133 of US’614 further claims the multifunctional molecule of 127, wherein the NKp30 binding domain comprises CDR sets with 100% identity to instantly claimed CDR pairings (see table below) (i.e. a bispecific antibody species that anticipates the instantly claimed antibody molecule that binds NKp30).
Instant (SEQ ID NOs)
US’614 (SEQ ID NOs)
19, 21, 23, 26, 28, 30
8053, 6001, 7315, 7326, 7327, 8689
19, 21, 23, 26, 28, 7395
8053, 6001, 7315, 7326, 7327, 8690
19, 7399, 23, 26, 28, 86
8053, 8688, 7315, 7326, 7327, 7329
19, 7399, 23, 26, 28, 113
8053, 8688, 7315, 7326, 7327, 8691
Regarding claims 47-50, claims 134-136 and 145-146 of US’614 claims the multifunctional molecule of 127 wherein the antigen binding domain to NKp30 comprises various VH/VL chains with 100% identity to instantly claimed sequences and combinations thereof within sequences that share identity with instantly claimed scFv sequences (see table below).
Instant (SEQ ID NOs)
US’614 (SEQ ID NOs)
1 or 2
7302 or 8030
9
8693
10
8694
11
8695
12
8696
13
7309
14
7305
15
8697
16
8698
17
8699
7386
8700
7387
8701
7388
8702
7389
8703
7390
8704
7391
8705
7392
8706
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
US 18/173,995
Claims 46-54, 57-58 and 63 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 136, 145, of copending Application No. 18/173,995 (herein US’995). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 46 and 51-52, the instant claim is drawn to a composition comprising an antibody molecule that binds to NKp30, and use inclusive or open-ended language to define the scope of the claim. Specifically, the term “comprising” is inclusive and does not exclude additional, unrecited elements or method steps (see MPEP 2111.03) (i.e. additional antigen binding domains). Claims 136 of US’995 claims a multifunctional molecule comprising a first antigen binding domain that binds to WT or mutant calreticulin and a second antigen domain that binds to NKp30 with HCDRs and LCDRs identical to instant claims and within scope of instantly claimed CDR pairings (see tables below) (i.e. a bispecific antibody species that anticipates the instantly claimed antibody molecule that binds NKp30). Claims 145 and 146 further claim CDR pairings within scope of the instant claims.
Claim 145 HCDR and LCDR sets
Instant (SEQ ID NOs)
US’995 (SEQ ID NOs)
19, 21, 23
7498, 6001, 7315
19, 7399, 23
7498, 7437, 7315
26, 28, 30
7326, 7327, 7416
26, 28, 7395
7326 or 7494, 7327 or 7496, 44
26, 28, 113
7326, 7327, 7447
26, 28, 86
7326, 7327, 7329
Claim 146 full CDR sets
Instant (SEQ ID NOs)
US’995 (SEQ ID NOs)
19, 21, 23, 26, 28, 30
7498, 6001, 7315, 7326, 7327, 7416
19, 21, 23, 26, 28, 7395
7498, 6001, 7315, 7494, 7496, 44
19, 7399, 23, 26, 28, 86
7498, 7437, 7315, 7326, 7327, 7329
19, 7399, 23, 26, 28, 113
7498, 7437, 7315, 7326, 7327, 7447
Regarding claims 47-50, claims 147 and 148 of US’995 claims the multifunctional molecule of 136 discussed above wherein the antigen binding domain to NKp30 comprises various VH/VL chains with 100% identity to instantly claimed sequences (see table below) with pairing that are within scope of the instant claims and further claims corresponding scFv sequences with 1005 identity to those instantly claimed.
Instant (SEQ ID NOs)
US’995 (SEQ ID NOs)
1 or 2
7302
9
7395
10
7397
11
7399
12
7401
13
7309
14
7305
15
7404
16
7405
17
7406
7386
7407
7387
7408
7388
7409
7389
7411
7390
7412
7391
7413
7392
7414
Regarding claims 53-55 (dependent on claim 52), claim 154 of US’995 claims the multifunctional molecule of claim 136 discussed above, wherein the molecule comprises a first and second immunoglobulin constant region (Fc region). Claim 155 of US’995 further claims the Fc interface between the first and second Fc regions comprise one or more of: a paired cavity-protuberance, an electrostatic interaction, or a strand-exchange, such that a greater ratio of heteromultimer:homomultimer forms relative to a dimerization of Fc regions with a non-engineered interface. Claim 156 further claims the composition of claim 154, wherein the first and/or second Fc regions comprise one or more mutations that result in reduced affinity for Fc receptor binding.
Regarding claims 57 and 63 (dependent on claim 52), claim 152 of US’995 claims the multifunctional molecule of claim 136 discussed above, wherein the molecule further comprises one or more of a cytokine or stromal modifying moiety.
Regarding claim 58 (dependent on claim 57), claim 153 of US’995 claims the cytokine molecule includes species within scope of the instant claim (e.g. IL-2, IL-7, IL-12, IL-15, IL-18, IL-21, interferon gamma or functional variants thereof).
Regarding claim 60 (dependent on claim 52), claim 162 of US’995 claims the molecule of claim 136 wherein the molecule binds to a myeloproliferative neoplasm cell (i.e. blood cancer cell) over a non-tumor cell (i.e. tumor targeting moiety).
Regarding claim 64 (dependent on claim 46), claim 164 of US’995 claims a polynucleotide sequence encoding the molecule of claim 136
Regarding claim 65 (dependent on claim 46), claim 165 of US’995 claims a patentably indistinct method of making the molecule of claim 136.
Regarding claim 66 (dependent on claim 46), claim 166 of US’995 claims a patentably indistinct pharmaceutical composition comprising the molecule of claim 136.
Regarding claim 67 (dependent on claim 46), claim 167 of US’995 claims a method of treating cancer using the molecule of claim 136.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
US 18/174,246
Claims 46-52, 60, 63 and 67 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 21, and 23-25 of copending Application No. 18/174,246 (herein US’246). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claims 46, 51-52, 60, 63, and 67, the instant claim is drawn to a composition comprising an antibody molecule that binds to NKp30, and use inclusive or open-ended language to define the scope of the claim. Specifically, the term “comprising” is inclusive and does not exclude additional, unrecited elements or method steps (see MPEP 2111.03) (i.e. additional antigen binding domains). Claim 1 of US’246 claims a method of treating cancer in a subject comprising administering a multifunctional molecule comprising a first antigen binding domain that binding to TCR beta constant domain 1 or 2 (TRBC1 or TRBC2) and a second antigen binding domain that binds to NKp30, wherein TRBC1 or TRBC2 are expressed by cancer cells (i.e. tumor targeting moiety). Claims 21 and 23 of US’246 further claim HCDRs and LCDRs with sets within scope of instant claim 46 (see table below). In summary, the bispecific molecule disclosed anticipates a species of antibody molecule that binds to NKp30 with scope of the instantly claimed genus and is therefore patentably indistinct.
Instant (SEQ ID NOs)
US’246 (SEQ ID NOs)
19, 21, 23, 26, 28, 30
[375, 377, 379, 382, 384, 386] or [417, 419, 421, 424, 426, 428]
19, 21, 23, 26, 28, 7395
[389, 391, 393, 396, 398, 400] or [403, 405, 407, 410, 412, 414]
19, 7399, 23, 26, 28, 86
[431, 433, 435, 438, 440, 442] or [445, 447, 449, 452, 454, 456]
19, 7399, 23, 26, 28, 113
[459, 461, 463, 466, 468, and 469] or [472,474,476,479,481, 483]
Regarding claims 47-50, claims 24 and 25 of US’246 further claim the method (i.e. multifunctional molecule) of claim 21 with VH/VL or scFv sequences for binding domains with 100% identity to instant sequences (see table below).
Instant (SEQ ID NOs)
US’246 (SEQ ID NOs)
1 or 2
357, 358, 359, 360, 7302
9
365
10
366
11
367
12
368
13
369, 7309
14
370, 7305
15
371
16
372
17
373
7386
485
7387
486
7388
487
7389
488
7390
489
7391
490
7392
491
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Allowable Subject Matter
Sequences comprising 100% identity to claimed CDRs, VH/VL pairings, and scFvs discussed above (i.e. with sufficient written description) are free from prior art.
Conclusion
No claims are currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNAH SUNSHINE whose telephone number is (571)270-7417. The examiner can normally be reached M-Th & Second Friday 8:30am-5pm EST.
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/HANNAH SUNSHINE/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647