DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claims 1, 2, 4-9, 23-25, 38, 40, 46, 50, 51, 61-65, 68-70, 121 and 122 are pending.
Claims 3, 10-22, 26-37, 39, 41-45, 47-49, 52-60, 66, 67, 71-120 and 123 have been cancelled.
Claims 4, 5, 8, 9, 23, 24, 46, 50, 61-65, 68-70, 121 and 122 have been amended.
Claims 1, 2, 4-9, 23-25, 38, 40, 46, 50, 51, 61-65, 68-70, 121 and 122 are examined on the merits.
Specification
3. The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed, a combinatorial treatment of multiple myeloma with a B cell maturation antigen and nirogacesat.
Claim Rejections - 35 USC § 112
4. 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.
5. Claims 5 and 6 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.
The purpose of the written description requirement is to ensure that the inventor had possession, at the time the invention was made, of the specific subject matter claimed. To satisfy the written description requirement, a patent specification must describe the claimed invention in sufficient detail that one skilled in the art can reasonably conclude that the inventor had possession of the claimed invention. See, e.g., Moba, B.V. v. Diamond Automation, Inc., 325 F.3d 1306, 1319, 66 USPQ2d 1429, 1438 (Fed. Cir. 2003); Vas-Cath, Inc. v. Mahurkar, 935 F.2d at 1563, 19 USPQ2d at 1116.
Claims 5 and 6 are drawn to a method comprising treating multiple myeloma (MM) with the administration of (i) one or more doses of an antibody, or antigen-binding fragment thereof, that specifically binds to a B cell maturation antigen (BCMA), and (ii) one or more doses of nirogascestat, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable domain comprising an amino acid sequence that is at least 80% or 90% identical to SEQ ID NO: 4 and a light chain variable domain comprising an amino acid sequence that is at least 80% or 90 identical to SEQ ID NO: 8.
The breadth of the instant claims encompasses binding agents, which read on alterations in the complementarity determining regions (CDRs). Therefore, the following grounds of rejection have been set forth.
It is noted that the specification discloses heavy chain variable domain, SEQ ID NO: 4 and light chain variable domain, SEQ ID NO: 8, see pages 29 and 30 within the Specification submitted March 22, 2024. One skilled in the art appreciates that traditional antibodies comprise two polypeptides, the so-called light and heavy chains. The antigen-combining site of an antibody is a three-dimensional structure that fully comprises six CDRs, three each from the light and heavy chains. The amino acid sequences of the CDRs are hypervariable, as the amino acid residues contained within the CDRs determine much of the antibody’s antigen-binding specificity. Antibodies having less than all six CDRs that form the antigen binding site of a conventional antibody in their proper context of VHs and VLs do not describe the particularly identifying structural feature of the antibody that correlates with the antibody’s ability to bind the target antigen or target epitope. Absent a description of the at least minimal structural features correlating with a functional ability to bind antigen which are shared by members of a genus commonly sharing this function, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish the one or more CDRs which should be combined such that a resultant antigen-binding domain is capable of binding the target antigen, as well functioning in concert with nirogacestat to treat multiple myeloma (MM).
Although screening techniques can be used to isolate variable heavy (VH) and variable light (VL) sequences that combine to form an antigen-binding domain capable of binding antigen, Applicant is reminded that the written description requirement of 35 U.S.C. 112 is severable from the enablement provision. As stated in Vas-Cath Inc. v. Mahurkar (CA FC) 19 USPQ2d 1111, 935 F2d 1555, “The purpose of the ‘written description’ requirement is broader than to merely explain how to ‘make and use’; the applicant must also convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.”
It is well established in the art that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope. The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proc. Natl. Acad. Sci. USA 79: 1979-1983, March 1982). Rudikoff teaches the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. MacCallum et al. (J. Mol. Biol. 262: 732-745, 1996) analyzed many different antibodies for interactions with antigen and state that although CDR3 of the heavy and light chain dominate, a number of residues outside the standard CDR definitions make antigen contacts (see page 733, right column (col.) and non-contacting residues within the CDRs coincide with residues as important in defining canonical backbone conformations (see page 735, left col.). De Pascalis et al. (The Journal of Immunology 169: 3076-3084, 2022) demonstrate that grafting of the CDRs into a human framework was performed by grafting CDR residues and maintaining framework residues that were deemed essential for preserving the structural integrity of the antigen binding site, see page 3079, right col. Although abbreviated CDR residues were used in the constructs, some residues in all 6 CDRs were used for the constructs, see page 3080, left col. The fact that not just one CDR is essential for antigen binding or maintaining the conformation of the antigen binding site, is underscored by Casset et al. (BBRC 307:198-205, 2003). Casset constructed a peptide mimetic of an anti-CD4 monoclonal antibody binding site by rational design and the peptide was designed with 27 residues formed by residues from 5 CDRs, see entire document. Casset also states that although CDR H3 is at the center of most if not all antigen interactions, clearly other CDRs play an important role in the recognition process, see page 199, left col. and this is demonstrated in this work by using all CDRs except L2 and additionally using a framework residue located just before the H3, see page 202, left col. Vajdos et al. (J. Mol. Biol. 320, 415-428, 2002), additionally state that antigen binding is primarily mediated by the CDRs more highly conserved framework segments which connect the CDRs are mainly involved in supporting the CDR loop conformations and in some cases framework residues also contact antigen, see page 416, left col. Chen et al. (J. Mol. Bio. 293: 865-881, 1999) describe high affinity variant antibodies binding to VEGF wherein the results show that the antigen binding site is almost entirely composed of residues from heavy chain CDRs, CDR-H1, H2, H3, see page 866. Wu et al. (J. Mol. Biol. 294: 151-162, 1999) state that it is difficult to predict which framework residues serve a critical role in maintaining affinity and specificity due in part to the large conformational change in antibodies that accompany antigen binding (page 152 left col.) but certain residues have been identified as important for maintaining conformation. Padlan et al. (PNAS 86:5938-5942, August 1989) described the crystal structure of an antibody-lysozyme complex where all 6 CDRs contribute at least one residue to binding and one residue in the framework is also in contact with antigen. Lastly, Lamminmaki et al. (JBC 276(39):36687-36694, 2001) describe the crystal structure of an anti-estradiol antibody in complex with estradiol where, although CDR3 of VH plays a prominent roll, all CDRs in the light chain make direct contact with antigen (even CDR2 of VL, which is rarely directly involved in hapten binding).
Thus, the state of the art recognized that it would be highly unpredictable that an antibody comprising less than all six CDRs from both the VH and VL regions with a desired specificity would bind the same antigen. Thus, the minimal structure which provides the function of binding appears to include six CDRs (three in the heavy chain variable region and three in the light chain variable region) from the same antibody. Unless all six CDRs for each binding domain for the B cell maturation antigen (BCMA) are present to successfully treat MM with nirogacestat, the instant claims are not able to perform the claimed function.
Accordingly, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish at least most of the members of the genus to which the claims are directed, and therefore the specification would not reasonably convey to the skilled artisan that Applicant was in possession of the claimed invention at the time the application was filed.
Applicant is invited to amend the claims to have 100% identity to both, VH and VL or to depend from claim 2, which recites all six CDRs with 100% identity. ant is invited to amend the claims to recite 6 CDRs for each binding domain targeting BCMA or 100% identity to both VH/VL for each binding domain (SEQ ID NOs: 4 and 8) to obviate this rejection.
Claim Rejections - 35 USC § 102
6. 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.
7. Claim(s) 1, 2, 8, 9, 23, 61-65 and 68 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by ClinicalTrials.gov ID NCT04126200, version 7 (version V7 dated February 17, 2020; first posted October 15, 2019), as evidenced by Trudel et al., (Annals of Oncology, Abstract 1105TiP, 30: Supplement 5, v447, October 2019). The Trials disclose “[b]elantamab mafodotin (GSK2857916); also referred to as GSK'916; is an antibody-drug conjugate (ADC) containing humanized anti-BCMA monoclonal antibody (mAb)...in combination with other anti-cancer drugs in participants with relapsed/refractory multiple myeloma (RRMM).”, see Brief Summary on page 10. As evidenced by Trudel, GSK’916 is a humanized (IgG1), and afucosylated, 1st sentence in Background.
The mAb can also be administered as a monotherapy, see page 16, 1st column (col.). One treatment arm reads on the administration of 1 or more escalating dose levels of GSK’916, see page 13, 1st col., 2nd row; and experimental segment bridging pages 14 and 15, 1st col. “GSK'916 (belantamab mafodotin) will be administered to participants via intravenous [IV] infusion…”, see page 15, 1st col. “GSK'916 (belantamab mafodotin) is available as powder for solution for infusion in unit dose strength of 100 mg per vial. It will be delivered as an intravenous solution.”, page 15, 2nd col.
The other anti-cancer drug may be nirogacestat, which is available as a 50 mg tablet administered twice per day, see page 15; and all Arms and Assigned Interventions.
Claim Rejections - 35 USC § 103
8. 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.
9. Claim(s) 1, 2, 4-9, 23-25, 38, 40, 46, 50, 51, 61-65, 68, 69 and 70 is/are rejected under 35 U.S.C. 103 as being unpatentable over Aardalen et al., WO 2020/261093 A1 (effectively filed 22 June 2020) as evidenced by Trudel et al., (Annals of Oncology, Abstract 1105TiP, 30: Supplement 5, v447, October 2019), and further in view of Sussman et al., US2017/0233484 (published August 17, 2017). Aardalen teaches administering a B cell maturation antigen (BCMA) binding molecule with a second therapeutic agent, wherein “the BCMA binding molecule and the second therapeutic agent are administered simultaneously, separately, or over a period of time” for the treatment of multiple myeloma (MM), see page 4, lines 25-29; page 7, lines 28-32; page 37, lines 14-19; page 47, lines 4-8. “BCMA binding molecules including multispecific binding molecules that comprise at least one ABD that binds to BCMA, e.g., multispecific antibodies, bispecific antibodies and other bispecific binding molecules.”, see page 14, last paragraph (para.). As evidenced by Trudel, GSK’916 is a humanized (IgG1), and afucosylated, 1st sentence in Background.
“The BCMA binding molecule can administered at varying doses.”, see page 2, line 19. “The BCMA binding molecule…can be administered to the subject in any effective way. In some embodiments, the BCMA binding molecule is administered to the subject intravenously.”, see page 3, lines 27-29.
“The BCMA binding molecule can administered at varying doses.”, see page 2, line 19. “The BCMA binding molecule…can be administered to the subject in any effective way. In some embodiments, the BCMA binding molecule is administered to the subject intravenously.”, see page 3, lines 27-29.
“In some embodiments, the BCMA binding molecule can be dosed a single time. In some embodiments, the BCMA molecule can be dosed twice. In some embodiments, the BCMA binding molecule can be dosed three times. In some embodiments, the BCMA binding molecule can be dosed four times.
In some embodiments, the BCMA binding molecule can be dosed for 1 week. In some embodiments, the BCMA binding molecule can be dosed for 2 weeks. In some embodiments, the BCMA binding molecule can be dosed for 3 weeks. In some embodiments, the BCMA binding molecule can be dosed for 4 weeks.”, see page 34, lines 12-19.
“[T]he second therapeutic agent is a gamma secretase inhibitor (GSI),” including PF-3084014, see page 4, line 30; page 38, lines 1-6; page 40, . PF-3084014 is art known as “…nirogacestat or (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino )-N-(1-(2-methyl-1-(neopentylamino )propan-2-yl)-1 H-imidazol-4-yl)pentanamide, or a pharmaceutically acceptable salt thereof.”, see page 40, lines 9-15; and page 48, line 11.
The second therapeutic agent, individually may be “…about 100 mg, or about 200 mg, or about 300 mg, or about 400 mg, or about 500 mg...”, see page 8, 2nd para.
“In some embodiments, the combination comprises about 100 mg, or about 200 mg, or about 300 mg, or about 400 mg, or about 500 mg of the second therapeutic agent. In some embodiments, the combination comprises about 2 mg, or about 10 mg, or about 20 mg, or about 40 mg, or about 80 mg, or about 160 mg, or about 320 mg of the compound; and about 100 mg, or about 200 mg, or about 300 mg, or about 400 mg, or about 500 mg of the second therapeutic agent.”, see page 8, lines 9-14. It is within the Examiner’s purview that the compound is the BCMA binding molecule, as the para. clearly denotes the second therapeutic agent. Accordingly, the dosage of the BCMA binding molecule compound reads on Applicant’s range.
A subject receiving the said treatment may also receive steroid therapy including dexamethasone, see page 51, lines 21-23.
“In other embodiments, a priming dose is equal to the first treatment dose. A priming dose can be administered in a single administration or, alternatively, administered over multiple administrations (e.g., two). In some embodiments, one third of a priming dose is administered on a first day, and two thirds of the priming dose is administered on a second day, 5 for example the day after the first day.”, see page 33, lines 1-5.
“The BCMA binding molecule can also be administered as a priming dose. This priming dose can be administered prior to the beginning of treatment with a treatment dose (e.g., a therapeutic dose that is therapeutically effective). A priming dose can be a dose that is equal to or less than a subsequently administered treatment dose. In some embodiments, the BCMA binding molecule is administered as a priming dose at a dose that is lower than the first treatment dose. A priming dose can be administered in a single administration, or split among two or more administrations. In some embodiments, a priming dose is split into two administrations given on two consecutive days. In some embodiments, one third of a priming dose is administered to a subject on one day, and two thirds of the priming dose is administered to the subject the next day.”, see page 4, 1st para.
“In some embodiments, the BCMA binding molecule can be dosed a single time. In some embodiments, the BCMA molecule can be dosed twice. In some embodiments, the BCMA binding molecule can be dosed three times. In some embodiments, the BCMA binding molecule can be dosed four times.
Aardalen does not teach the BCMA antibody or antigen-binding fragment thereof, comprises a heavy chain variable region comprising a CDR1 comprising SEQ ID NO: 1, a CDR2 comprising SEQ ID NO: 2, and a CDR3 comprising SEQ ID NO: 3, and a light chain variable domain comprising a CDR1 comprising SEQ ID NO: 5, a CDR2 comprising SEQ ID NO: 6, and a CDR3 comprising SEQ ID NO: 7, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable domain comprising an amino acid sequence that is at least 80% or 90% identical to SEQ ID NO: 4 and a light chain variable domain comprising an amino acid sequence that is at least 80% or 90% identical to SEQ ID NO: 8.
Aardalen does not the administration of the BCMA antibody in induction doses independently administered in the said dosages cited in claim 46, as well as one or more maintenance does independently with two or mores of nirogacestat independently administered at a frequency of about one a day to about four times a day.
However, Sussman teaches the BCMA antibody or antigen-binding fragment thereof comprising an amino acid that is 100% identical to Applicant’s heavy chain variable domain, SEQ ID NO: 4 and an amino acid that is 100% identical to Applicant’s light chain variable domain, SEQ ID NO: 8, as well as the CDRs therein, see sequence alignments at the close of the instant rejection.
It would have been obvious to one of ordinary skill in the art at the effective filing date of the claimed invention to substitute the BCMA antibody molecule of Aardalen with the BCMA antibody compound of Sussman with known structure given it has successfully targeted BCMA antigen for treatment, see the entire document.
One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by teachings in Sussman that the target of the antibodies with known CDRs is art recognized as a plausible alternative, as well as the antibody within a pharmaceutical composition is suitable for MM treatment, see page 2, section 0011; and page 17, section 0163.
It would have been obvious to one of ordinary skill in the art at the effective filing date of the claimed invention to arrive at the dosing schedule inclusive of induction doses at designated amounts independently administered during an induction phase, maintenance doses independently administered during a maintenance phase after the induction phase at designated time points.
One of ordinary skill in the art would have been motivated to administer the therapeutic agents at the cited dosages within in the instant claims to individuals with MM in light of Aardalen at the designated dosage ranges and time points cited within the claims with a reasonable expectation of success by teachings well known that dosages of any pharmaceutical composition may be adjusted and optimized. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by teachings in the art, wherein Aardalen explicitly teaches “[t]he BCMA binding molecule can administered at varying doses” and “the BCMA binding molecule and/or additional agent(s) can be administered in an amount or dose that is higher, lower or the same than the amount of dosage of each agent used individually”, see page 2, line 19; page 36, lines 21-23, respectively; and entire document.
RESULT 1 from 1fus2fus3.align450.rag database.
BEG60540
(NOTE: this sequence has 27 duplicates in the database searched.
See complete list at the end of this report)
ID BEG60540 standard; protein; 121 AA.
XX
AC BEG60540;
XX
DT 02-NOV-2017 (first entry)
XX
DE Human anti-BCMA antibody heavy chain variable region, SEQ ID 13.
XX
KW APRIL receptor; B-cell maturation antigen; BCMA protein; CD269;
KW allergic rhinitis; antibody; antibody therapy; asthma; atopic dermatitis;
KW cancer; cytostatic; graft versus host disease; graves disease;
KW hashimotos disease; heavy chain variable region; hematological neoplasm;
KW hodgkins disease; immune disorder; immunomodulator;
KW insulin dependent diabetes; leukemia; lymphoma; macroglobulinemia;
KW multiple myeloma; multiple sclerosis;
KW mycobacterium tuberculosis infection; myelodysplastic syndrome;
KW myeloproliferative disorder; non-hodgkin lymphoma; pharmaceutical;
KW primary biliary cirrhosis; psoriasis; rheumatoid arthritis;
KW sjoegrens syndrome; systemic lupus erythematosus; therapeutic;
KW thrombocytopenic purpura; wegener granulomatosis.
XX
OS Homo sapiens.
XX
CC PN US2017233484-A1.
XX
CC PD 17-AUG-2017.
XX
CC PF 16-FEB-2017; 2017US-00434921.
XX
PR 17-FEB-2016; 2016US-0296594P.
PR 16-SEP-2016; 2016US-0396084P.
XX
CC PA (SEGE ) SEATTLE GENETICS INC.
XX
CC PI Sussman D, Ryan M, Westendorf L, Feldhaus M;
XX
DR WPI; 2017-56594M/57.
XX
CC PT New humanized, chimeric or veneered antibody used in pharmaceutical
CC PT composition for treating cancer or immune disorder e.g. multiple myeloma,
CC PT rheumatoid arthritis, and asthma comprises mature heavy and light chain
CC PT variable region.
XX
CC PS Claim 2; SEQ ID NO 13; 88pp; English.
XX
CC The present invention relates to a novel humanized, chimeric or veneered
CC antibody useful for treating cancer or immune disorder. The invention
CC cancer is chosen from multiple myeloma, hematological cancer, myeloma,
CC leukemia, non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma or lymphoma,
CC myelodysplastic syndromes (MDS), myeloproliferative syndromes (MPS),
CC Waldenstrom's macroglobulinemia or Burkett's lymphoma, immune disorder is
CC chosen from rheumatoid arthritis, systemic lupus erythematosus (SLE),
CC type I diabetes, asthma, atopic dermatitis, allergic rhinitis,
CC thrombocytopenic purpura, multiple sclerosis, psoriasis, Sjogren's
CC syndrome, Hashimoto's thyroiditis, Grave's disease, primary biliary
CC cirrhosis, Wegener's granulomatosis, tuberculosis, and graft versus host
CC disease. The present sequence is a human anti-BCMA antibody heavy chain
CC variable region, used in the invention for treating cancer or immune
CC disorder.
XX
SQ Sequence 121 AA;
Query Match 87.7%; Score 175.4; Length 121;
Best Local Similarity 42.5%;
Matches 34; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 DYYIH--------------YINPNSGYTNYAQKFQG------------------------ 22
||||| |||||||||||||||||
Db 31 DYYIHWVRQAPGQGLEWIGYINPNSGYTNYAQKFQGRATMTADKSINTAYVELSRLRSDD 90
Qy 23 --------YMWERVTGFFDF 34
||||||||||||
Db 91 TAVYFCTRYMWERVTGFFDF 110
RESULT 2 from 5fus6fus7.align450.rag database.
BEG60546
(NOTE: this sequence has 12 duplicates in the database searched.
See complete list at the end of this report)
ID BEG60546 standard; protein; 108 AA.
XX
AC BEG60546;
XX
DT 02-NOV-2017 (first entry)
XX
DE Anti-BCMA antibody light chain variable region, SEQ ID 19.
XX
KW APRIL receptor; B-cell maturation antigen; BCMA protein; CD269;
KW allergic rhinitis; antibody; antibody therapy; asthma; atopic dermatitis;
KW cancer; cytostatic; graft versus host disease; graves disease;
KW hashimotos disease; hematological neoplasm; hodgkins disease;
KW immune disorder; immunomodulator; insulin dependent diabetes; leukemia;
KW light chain variable region; lymphoma; macroglobulinemia;
KW multiple myeloma; multiple sclerosis;
KW mycobacterium tuberculosis infection; myelodysplastic syndrome;
KW myeloproliferative disorder; non-hodgkin lymphoma; pharmaceutical;
KW primary biliary cirrhosis; psoriasis; rheumatoid arthritis;
KW sjoegrens syndrome; systemic lupus erythematosus; therapeutic;
KW thrombocytopenic purpura; wegener granulomatosis.
XX
OS Unidentified.
XX
CC PN US2017233484-A1.
XX
CC PD 17-AUG-2017.
XX
CC PF 16-FEB-2017; 2017US-00434921.
XX
PR 17-FEB-2016; 2016US-0296594P.
PR 16-SEP-2016; 2016US-0396084P.
XX
CC PA (SEGE ) SEATTLE GENETICS INC.
XX
CC PI Sussman D, Ryan M, Westendorf L, Feldhaus M;
XX
DR WPI; 2017-56594M/57.
XX
CC PT New humanized, chimeric or veneered antibody used in pharmaceutical
CC PT composition for treating cancer or immune disorder e.g. multiple myeloma,
CC PT rheumatoid arthritis, and asthma comprises mature heavy and light chain
CC PT variable region.
XX
CC PS Claim 2; SEQ ID NO 19; 88pp; English.
XX
CC The present invention relates to a novel humanized, chimeric or veneered
CC antibody useful for treating cancer or immune disorder. The invention
CC cancer is chosen from multiple myeloma, hematological cancer, myeloma,
CC leukemia, non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma or lymphoma,
CC myelodysplastic syndromes (MDS), myeloproliferative syndromes (MPS),
CC Waldenstrom's macroglobulinemia or Burkett's lymphoma, immune disorder is
CC chosen from rheumatoid arthritis, systemic lupus erythematosus (SLE),
CC type I diabetes, asthma, atopic dermatitis, allergic rhinitis,
CC thrombocytopenic purpura, multiple sclerosis, psoriasis, Sjogren's
CC syndrome, Hashimoto's thyroiditis, Grave's disease, primary biliary
CC cirrhosis, Wegener's granulomatosis, tuberculosis, and graft versus host
CC disease. The present sequence is an anti-BCMA antibody light chain
CC variable region, used in the invention for treating cancer or immune
CC disorder.
XX
SQ Sequence 108 AA;
Query Match 81.6%; Score 109.3; Length 108;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 LASEDISDDLA---------------TTSSLQS--------------------------- 18
||||||||||| |||||||
Db 24 LASEDISDDLAWYQQKPGKAPKVLVYTTSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDF 83
Qy 19 -----QQTYKFPPT 27
|||||||||
Db 84 ATYFCQQTYKFPPT 97
RESULT 1 from 4.rag database.
BEG60540
(NOTE: this sequence has 27 duplicates in the database searched.
See complete list at the end of this report)
ID BEG60540 standard; protein; 121 AA.
XX
AC BEG60540;
XX
DT 02-NOV-2017 (first entry)
XX
DE Human anti-BCMA antibody heavy chain variable region, SEQ ID 13.
XX
KW APRIL receptor; B-cell maturation antigen; BCMA protein; CD269;
KW allergic rhinitis; antibody; antibody therapy; asthma; atopic dermatitis;
KW cancer; cytostatic; graft versus host disease; graves disease;
KW hashimotos disease; heavy chain variable region; hematological neoplasm;
KW hodgkins disease; immune disorder; immunomodulator;
KW insulin dependent diabetes; leukemia; lymphoma; macroglobulinemia;
KW multiple myeloma; multiple sclerosis;
KW mycobacterium tuberculosis infection; myelodysplastic syndrome;
KW myeloproliferative disorder; non-hodgkin lymphoma; pharmaceutical;
KW primary biliary cirrhosis; psoriasis; rheumatoid arthritis;
KW sjoegrens syndrome; systemic lupus erythematosus; therapeutic;
KW thrombocytopenic purpura; wegener granulomatosis.
XX
OS Homo sapiens.
XX
CC PN US2017233484-A1.
XX
CC PD 17-AUG-2017.
XX
CC PF 16-FEB-2017; 2017US-00434921.
XX
PR 17-FEB-2016; 2016US-0296594P.
PR 16-SEP-2016; 2016US-0396084P.
XX
CC PA (SEGE ) SEATTLE GENETICS INC.
XX
CC PI Sussman D, Ryan M, Westendorf L, Feldhaus M;
XX
DR WPI; 2017-56594M/57.
XX
CC PT New humanized, chimeric or veneered antibody used in pharmaceutical
CC PT composition for treating cancer or immune disorder e.g. multiple myeloma,
CC PT rheumatoid arthritis, and asthma comprises mature heavy and light chain
CC PT variable region.
XX
CC PS Claim 2; SEQ ID NO 13; 88pp; English.
XX
CC The present invention relates to a novel humanized, chimeric or veneered
CC antibody useful for treating cancer or immune disorder. The invention
CC cancer is chosen from multiple myeloma, hematological cancer, myeloma,
CC leukemia, non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma or lymphoma,
CC myelodysplastic syndromes (MDS), myeloproliferative syndromes (MPS),
CC Waldenstrom's macroglobulinemia or Burkett's lymphoma, immune disorder is
CC chosen from rheumatoid arthritis, systemic lupus erythematosus (SLE),
CC type I diabetes, asthma, atopic dermatitis, allergic rhinitis,
CC thrombocytopenic purpura, multiple sclerosis, psoriasis, Sjogren's
CC syndrome, Hashimoto's thyroiditis, Grave's disease, primary biliary
CC cirrhosis, Wegener's granulomatosis, tuberculosis, and graft versus host
CC disease. The present sequence is a human anti-BCMA antibody heavy chain
CC variable region, used in the invention for treating cancer or immune
CC disorder.
XX
SQ Sequence 121 AA;
Query Match 100.0%; Score 652; Length 121;
Best Local Similarity 100.0%;
Matches 121; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKLSCKASGYTFTDYYIHWVRQAPGQGLEWIGYINPNSGYTNY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKLSCKASGYTFTDYYIHWVRQAPGQGLEWIGYINPNSGYTNY 60
Qy 61 AQKFQGRATMTADKSINTAYVELSRLRSDDTAVYFCTRYMWERVTGFFDFWGQGTMVTVS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AQKFQGRATMTADKSINTAYVELSRLRSDDTAVYFCTRYMWERVTGFFDFWGQGTMVTVS 120
Qy 121 S 121
|
Db 121 S 121
RESULT 1 from 8.rag database.
BEG60546
(NOTE: this sequence has 12 duplicates in the database searched.
See complete list at the end of this report)
ID BEG60546 standard; protein; 108 AA.
XX
AC BEG60546;
XX
DT 02-NOV-2017 (first entry)
XX
DE Anti-BCMA antibody light chain variable region, SEQ ID 19.
XX
KW APRIL receptor; B-cell maturation antigen; BCMA protein; CD269;
KW allergic rhinitis; antibody; antibody therapy; asthma; atopic dermatitis;
KW cancer; cytostatic; graft versus host disease; graves disease;
KW hashimotos disease; hematological neoplasm; hodgkins disease;
KW immune disorder; immunomodulator; insulin dependent diabetes; leukemia;
KW light chain variable region; lymphoma; macroglobulinemia;
KW multiple myeloma; multiple sclerosis;
KW mycobacterium tuberculosis infection; myelodysplastic syndrome;
KW myeloproliferative disorder; non-hodgkin lymphoma; pharmaceutical;
KW primary biliary cirrhosis; psoriasis; rheumatoid arthritis;
KW sjoegrens syndrome; systemic lupus erythematosus; therapeutic;
KW thrombocytopenic purpura; wegener granulomatosis.
XX
OS Unidentified.
XX
CC PN US2017233484-A1.
XX
CC PD 17-AUG-2017.
XX
CC PF 16-FEB-2017; 2017US-00434921.
XX
PR 17-FEB-2016; 2016US-0296594P.
PR 16-SEP-2016; 2016US-0396084P.
XX
CC PA (SEGE ) SEATTLE GENETICS INC.
XX
CC PI Sussman D, Ryan M, Westendorf L, Feldhaus M;
XX
DR WPI; 2017-56594M/57.
XX
CC PT New humanized, chimeric or veneered antibody used in pharmaceutical
CC PT composition for treating cancer or immune disorder e.g. multiple myeloma,
CC PT rheumatoid arthritis, and asthma comprises mature heavy and light chain
CC PT variable region.
XX
CC PS Claim 2; SEQ ID NO 19; 88pp; English.
XX
CC The present invention relates to a novel humanized, chimeric or veneered
CC antibody useful for treating cancer or immune disorder. The invention
CC cancer is chosen from multiple myeloma, hematological cancer, myeloma,
CC leukemia, non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma or lymphoma,
CC myelodysplastic syndromes (MDS), myeloproliferative syndromes (MPS),
CC Waldenstrom's macroglobulinemia or Burkett's lymphoma, immune disorder is
CC chosen from rheumatoid arthritis, systemic lupus erythematosus (SLE),
CC type I diabetes, asthma, atopic dermatitis, allergic rhinitis,
CC thrombocytopenic purpura, multiple sclerosis, psoriasis, Sjogren's
CC syndrome, Hashimoto's thyroiditis, Grave's disease, primary biliary
CC cirrhosis, Wegener's granulomatosis, tuberculosis, and graft versus host
CC disease. The present sequence is an anti-BCMA antibody light chain
CC variable region, used in the invention for treating cancer or immune
CC disorder.
XX
SQ Sequence 108 AA;
Query Match 100.0%; Score 559; Length 108;
Best Local Similarity 100.0%;
Matches 108; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSVSASVGDRVTITCLASEDISDDLAWYQQKPGKAPKVLVYTTSSLQSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSVSASVGDRVTITCLASEDISDDLAWYQQKPGKAPKVLVYTTSSLQSGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYFCQQTYKFPPTFGGGTKVEIKR 108
||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFATYFCQQTYKFPPTFGGGTKVEIKR 108
10. Claim(s) 1, 2, 4-9, 23-25, 38, 40, 46, 50, 51, 61-65 and 68-70 is/are rejected under 35 U.S.C. 103 as being unpatentable over ClinicalTrials.gov ID NCT04126200, version 7 (version V7 dated February 17, 2020; first posted October 15, 2019), as evidenced by Trudel et al., (Annals of Oncology, Abstract 1105TiP, 30: Supplement 5, v447, October 2019), and further in view of Aardalen et al., WO 2020/261093 A1 (effectively filed 22 June 2020) and Sussman et al., US2017/0233484 (published August 17, 2017). The Trials teach “[b]elantamab mafodotin (GSK2857916); also referred to as GSK'916; is an antibody-drug conjugate (ADC) containing humanized anti-BCMA monoclonal antibody (mAb)...in combination with other anti-cancer drugs in participants with relapsed/refractory multiple myeloma (RRMM).”, see Brief Summary on page 10. As evidenced by Trudel, GSK’916 is a humanized (IgG1), and afucosylated, 1st sentence in Background.
The mAb can also be administered as a monotherapy, see page 16, 1st column (col.). One treatment arm reads on the administration of 1 or more escalating dose levels of GSK’916, see page 13, 1st col., 2nd row; and experimental segment bridging pages 14 and 15, 1st col. “GSK'916 (belantamab mafodotin) will be administered to participants via intravenous [IV] infusion…”, see page 15, 1st col. “GSK'916 (belantamab mafodotin) is available as powder for solution for infusion in unit dose strength of 100 mg per vial. It will be delivered as an intravenous solution.”, page 15, 2nd col.
The other anti-cancer drug may be nirogacestat, which is available as a 50 mg tablet administered twice per day, see page 15; and all Arms and Assigned Interventions.
The Trials do not teach the BCMA antibody or antigen-binding fragment thereof, comprises a heavy chain variable region comprising a CDR1 comprising SEQ ID NO: 1, a CDR2 comprising SEQ ID NO: 2, and a CDR3 comprising SEQ ID NO: 3, and a light chain variable domain comprising a CDR1 comprising SEQ ID NO: 5, a CDR2 comprising SEQ ID NO: 6, and a CDR3 comprising SEQ ID NO: 7, wherein the antibody or the antigen-binding fragment thereof comprises a heavy chain variable domain comprising an amino acid sequence that is at least 80% or 90% identical to SEQ ID NO: 4 and a light chain variable domain comprising an amino acid sequence that is at least 80% or 90% identical to SEQ ID NO: 8.
Nor, do the Trials teach the administration of the BCMA antibody in induction doses independently administered in the said dosages cited in claim 46, as well as one or more maintenance does independently with two or mores of nirogacestat independently administered at a frequency of about one a day to about four times a day or one or more doses of dexamethasone to the subject.
However, Aardalen teaches administering a B cell maturation antigen (BCMA) binding molecule with a second therapeutic agent, wherein “the BCMA binding molecule and the second therapeutic agent are administered simultaneously, separately, or over a period of time” for the treatment of multiple myeloma (MM), see page 4, lines 25-29; page 7, lines 28-32; page 37, lines 14-19; page 47, lines 4-8. “BCMA binding molecules including multispecific binding molecules that comprise at least one ABD that binds to BCMA, e.g., multispecific antibodies, bispecific antibodies and other bispecific binding molecules.”, see page 14, last paragraph (para.).
“The BCMA binding molecule can administered at varying doses.”, see page 2, line 19. “The BCMA binding molecule…can be administered to the subject in any effective way. In some embodiments, the BCMA binding molecule is administered to the subject intravenously.”, see page 3, lines 27-29.
“The BCMA binding molecule can administered at varying doses.”, see page 2, line 19. “The BCMA binding molecule…can be administered to the subject in any effective way. In some embodiments, the BCMA binding molecule is administered to the subject intravenously.”, see page 3, lines 27-29.
“In some embodiments, the BCMA binding molecule can be dosed a single time. In some embodiments, the BCMA molecule can be dosed twice. In some embodiments, the BCMA binding molecule can be dosed three times. In some embodiments, the BCMA binding molecule can be dosed four times.
In some embodiments, the BCMA binding molecule can be dosed for 1 week. In some embodiments, the BCMA binding molecule can be dosed for 2 weeks. In some embodiments, the BCMA binding molecule can be dosed for 3 weeks. In some embodiments, the BCMA binding molecule can be dosed for 4 weeks.”, see page 34, lines 12-19.
“In some embodiments, the combination comprises about 100 mg, or about 200 mg, or about 300 mg, or about 400 mg, or about 500 mg of the second therapeutic agent. In some embodiments, the combination comprises about 2 mg, or about 10 mg, or about 20 mg, or about 40 mg, or about 80 mg, or about 160 mg, or about 320 mg of the compound; and about 100 mg, or about 200 mg, or about 300 mg, or about 400 mg, or about 500 mg of the second therapeutic agent.”, see page 8, lines 9-14. It is within the Examiner’s purview that the compound is the BCMA binding molecule, as the para. clearly denotes the second therapeutic agent. Accordingly, the dosage of the BCMA binding molecule compound reads on Applicant’s range.
“[T]he second therapeutic agent is a gamma secretase inhibitor (GSI),” including PF-3084014, see page 4, line 30; page 38, lines 1-6; page 40, . PF-3084014 is art known as “…nirogacestat or (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino )-N-(1-(2-methyl-1-(neopentylamino )propan-2-yl)-1 H-imidazol-4-yl)pentanamide, or a pharmaceutically acceptable salt thereof.”, see page 40, lines 9-15; page 48, line 11; .
The second therapeutic agent, individually may be “…about 100 mg, or about 200 mg, or about 300 mg, or about 400 mg, or about 500 mg...”, see page 8, 2nd para.
A subject receiving the said treatment may also receive steroid therapy including dexamethasone, see page 51, lines 21-23.
“The BCMA binding molecule can also be administered as a priming dose. This priming dose can be administered prior to the beginning of treatment with a treatment dose (e.g., a therapeutic dose that is therapeutically effective). A priming dose can be a dose that is equal to or less than a subsequently administered treatment dose. In some embodiments, the BCMA binding molecule is administered as a priming dose at a dose that is lower than the first treatment dose. A priming dose can be administered in a single administration, or split among two or more administrations. In some embodiments, a priming dose is split into two administrations given on two consecutive days. In some embodiments, one third of a priming dose is administered to a subject on one day, and two thirds of the priming dose is administered to the subject the next day.”, see page 4, 1st para.
“In some embodiments, the BCMA binding molecule can be dosed a single time. In some embodiments, the BCMA molecule can be dosed twice. In some embodiments, the BCMA binding molecule can be dosed three times. In some embodiments, the BCMA binding molecule can be dosed four times.
However, Sussman teaches the BCMA antibody or antigen-binding fragment thereof comprising an amino acid that is 100% identical to Applicant’s heavy chain variable domain, SEQ ID NO: 4 and an amino acid that is 100% identical to Applicant’s light chain variable domain, SEQ ID NO: 8, as well as the CDRs therein.
It would have been obvious to one of ordinary skill in the art at the effective filing date of the claimed invention to substitute the BCMA antibody molecule of Aardalen with the BCMA antibody compound of Sussman with known structure given it has successfully targeted BCMA antigen for treatment, see the entire document.
It would have been obvious to one of ordinary skill in the art at the effective filing date of the claimed invention to arrive at the dosing schedule inclusive of induction doses at designated amounts independently administered during an induction phase, maintenance doses independently administered during a maintenance phase after the induction phase at designated time points.
One of ordinary skill in the art would have been motivated to administer the therapeutic agents at the cited dosages within in the instant claims to individuals with MM in light of Aardalen at the designated dosage ranges and time points cited within the claims with a reasonable expectation of success by teachings well known that dosages of any pharmaceutical composition may be adjusted and optimized. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by teachings in the art, wherein Aardalen explicitly teaches “[t]he BCMA binding molecule can administered at varying doses” and “the BCMA binding molecule and/or additional agent(s) can be administered in an amount or dose that is higher, lower or the same than the amount of dosage of each agent used individually”, see page 2, line 19; page 36, lines 21-23, respectively; and entire document.
RESULT 1 from 1fus2fus3.align450.rag database.
BEG60540
(NOTE: this sequence has 27 duplicates in the database searched.
See complete list at the end of this report)
ID BEG60540 standard; protein; 121 AA.
XX
AC BEG60540;
XX
DT 02-NOV-2017 (first entry)
XX
DE Human anti-BCMA antibody heavy chain variable region, SEQ ID 13.
XX
KW APRIL receptor; B-cell maturation antigen; BCMA protein; CD269;
KW allergic rhinitis; antibody; antibody therapy; asthma; atopic dermatitis;
KW cancer; cytostatic; graft versus host disease; graves disease;
KW hashimotos disease; heavy chain variable region; hematological neoplasm;
KW hodgkins disease; immune disorder; immunomodulator;
KW insulin dependent diabetes; leukemia; lymphoma; macroglobulinemia;
KW multiple myeloma; multiple sclerosis;
KW mycobacterium tuberculosis infection; myelodysplastic syndrome;
KW myeloproliferative disorder; non-hodgkin lymphoma; pharmaceutical;
KW primary biliary cirrhosis; psoriasis; rheumatoid arthritis;
KW sjoegrens syndrome; systemic lupus erythematosus; therapeutic;
KW thrombocytopenic purpura; wegener granulomatosis.
XX
OS Homo sapiens.
XX
CC PN US2017233484-A1.
XX
CC PD 17-AUG-2017.
XX
CC PF 16-FEB-2017; 2017US-00434921.
XX
PR 17-FEB-2016; 2016US-0296594P.
PR 16-SEP-2016; 2016US-0396084P.
XX
CC PA (SEGE ) SEATTLE GENETICS INC.
XX
CC PI Sussman D, Ryan M, Westendorf L, Feldhaus M;
XX
DR WPI; 2017-56594M/57.
XX
CC PT New humanized, chimeric or veneered antibody used in pharmaceutical
CC PT composition for treating cancer or immune disorder e.g. multiple myeloma,
CC PT rheumatoid arthritis, and asthma comprises mature heavy and light chain
CC PT variable region.
XX
CC PS Claim 2; SEQ ID NO 13; 88pp; English.
XX
CC The present invention relates to a novel humanized, chimeric or veneered
CC antibody useful for treating cancer or immune disorder. The invention
CC cancer is chosen from multiple myeloma, hematological cancer, myeloma,
CC leukemia, non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma or lymphoma,
CC myelodysplastic syndromes (MDS), myeloproliferative syndromes (MPS),
CC Waldenstrom's macroglobulinemia or Burkett's lymphoma, immune disorder is
CC chosen from rheumatoid arthritis, systemic lupus erythematosus (SLE),
CC type I diabetes, asthma, atopic dermatitis, allergic rhinitis,
CC thrombocytopenic purpura, multiple sclerosis, psoriasis, Sjogren's
CC syndrome, Hashimoto's thyroiditis, Grave's disease, primary biliary
CC cirrhosis, Wegener's granulomatosis, tuberculosis, and graft versus host
CC disease. The present sequence is a human anti-BCMA antibody heavy chain
CC variable region, used in the invention for treating cancer or immune
CC disorder.
XX
SQ Sequence 121 AA;
Query Match 87.7%; Score 175.4; Length 121;
Best Local Similarity 42.5%;
Matches 34; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 DYYIH--------------YINPNSGYTNYAQKFQG------------------------ 22
||||| |||||||||||||||||
Db 31 DYYIHWVRQAPGQGLEWIGYINPNSGYTNYAQKFQGRATMTADKSINTAYVELSRLRSDD 90
Qy 23 --------YMWERVTGFFDF 34
||||||||||||
Db 91 TAVYFCTRYMWERVTGFFDF 110
RESULT 2 from 5fus6fus7.align450.rag database.
BEG60546
(NOTE: this sequence has 12 duplicates in the database searched.
See complete list at the end of this report)
ID BEG60546 standard; protein; 108 AA.
XX
AC BEG60546;
XX
DT 02-NOV-2017 (first entry)
XX
DE Anti-BCMA antibody light chain variable region, SEQ ID 19.
XX
KW APRIL receptor; B-cell maturation antigen; BCMA protein; CD269;
KW allergic rhinitis; antibody; antibody therapy; asthma; atopic dermatitis;
KW cancer; cytostatic; graft versus host disease; graves disease;
KW hashimotos disease; hematological neoplasm; hodgkins disease;
KW immune disorder; immunomodulator; insulin dependent diabetes; leukemia;
KW light chain variable region; lymphoma; macroglobulinemia;
KW multiple myeloma; multiple sclerosis;
KW mycobacterium tuberculosis infection; myelodysplastic syndrome;
KW myeloproliferative disorder; non-hodgkin lymphoma; pharmaceutical;
KW primary biliary cirrhosis; psoriasis; rheumatoid arthritis;
KW sjoegrens syndrome; systemic lupus erythematosus; therapeutic;
KW thrombocytopenic purpura; wegener granulomatosis.
XX
OS Unidentified.
XX
CC PN US2017233484-A1.
XX
CC PD 17-AUG-2017.
XX
CC PF 16-FEB-2017; 2017US-00434921.
XX
PR 17-FEB-2016; 2016US-0296594P.
PR 16-SEP-2016; 2016US-0396084P.
XX
CC PA (SEGE ) SEATTLE GENETICS INC.
XX
CC PI Sussman D, Ryan M, Westendorf L, Feldhaus M;
XX
DR WPI; 2017-56594M/57.
XX
CC PT New humanized, chimeric or veneered antibody used in pharmaceutical
CC PT composition for treating cancer or immune disorder e.g. multiple myeloma,
CC PT rheumatoid arthritis, and asthma comprises mature heavy and light chain
CC PT variable region.
XX
CC PS Claim 2; SEQ ID NO 19; 88pp; English.
XX
CC The present invention relates to a novel humanized, chimeric or veneered
CC antibody useful for treating cancer or immune disorder. The invention
CC cancer is chosen from multiple myeloma, hematological cancer, myeloma,
CC leukemia, non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma or lymphoma,
CC myelodysplastic syndromes (MDS), myeloproliferative syndromes (MPS),
CC Waldenstrom's macroglobulinemia or Burkett's lymphoma, immune disorder is
CC chosen from rheumatoid arthritis, systemic lupus erythematosus (SLE),
CC type I diabetes, asthma, atopic dermatitis, allergic rhinitis,
CC thrombocytopenic purpura, multiple sclerosis, psoriasis, Sjogren's
CC syndrome, Hashimoto's thyroiditis, Grave's disease, primary biliary
CC cirrhosis, Wegener's granulomatosis, tuberculosis, and graft versus host
CC disease. The present sequence is an anti-BCMA antibody light chain
CC variable region, used in the invention for treating cancer or immune
CC disorder.
XX
SQ Sequence 108 AA;
Query Match 81.6%; Score 109.3; Length 108;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 LASEDISDDLA---------------TTSSLQS--------------------------- 18
||||||||||| |||||||
Db 24 LASEDISDDLAWYQQKPGKAPKVLVYTTSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDF 83
Qy 19 -----QQTYKFPPT 27
|||||||||
Db 84 ATYFCQQTYKFPPT 97
RESULT 1 from 4.rag database.
BEG60540
(NOTE: this sequence has 27 duplicates in the database searched.
See complete list at the end of this report)
ID BEG60540 standard; protein; 121 AA.
XX
AC BEG60540;
XX
DT 02-NOV-2017 (first entry)
XX
DE Human anti-BCMA antibody heavy chain variable region, SEQ ID 13.
XX
KW APRIL receptor; B-cell maturation antigen; BCMA protein; CD269;
KW allergic rhinitis; antibody; antibody therapy; asthma; atopic dermatitis;
KW cancer; cytostatic; graft versus host disease; graves disease;
KW hashimotos disease; heavy chain variable region; hematological neoplasm;
KW hodgkins disease; immune disorder; immunomodulator;
KW insulin dependent diabetes; leukemia; lymphoma; macroglobulinemia;
KW multiple myeloma; multiple sclerosis;
KW mycobacterium tuberculosis infection; myelodysplastic syndrome;
KW myeloproliferative disorder; non-hodgkin lymphoma; pharmaceutical;
KW primary biliary cirrhosis; psoriasis; rheumatoid arthritis;
KW sjoegrens syndrome; systemic lupus erythematosus; therapeutic;
KW thrombocytopenic purpura; wegener granulomatosis.
XX
OS Homo sapiens.
XX
CC PN US2017233484-A1.
XX
CC PD 17-AUG-2017.
XX
CC PF 16-FEB-2017; 2017US-00434921.
XX
PR 17-FEB-2016; 2016US-0296594P.
PR 16-SEP-2016; 2016US-0396084P.
XX
CC PA (SEGE ) SEATTLE GENETICS INC.
XX
CC PI Sussman D, Ryan M, Westendorf L, Feldhaus M;
XX
DR WPI; 2017-56594M/57.
XX
CC PT New humanized, chimeric or veneered antibody used in pharmaceutical
CC PT composition for treating cancer or immune disorder e.g. multiple myeloma,
CC PT rheumatoid arthritis, and asthma comprises mature heavy and light chain
CC PT variable region.
XX
CC PS Claim 2; SEQ ID NO 13; 88pp; English.
XX
CC The present invention relates to a novel humanized, chimeric or veneered
CC antibody useful for treating cancer or immune disorder. The invention
CC cancer is chosen from multiple myeloma, hematological cancer, myeloma,
CC leukemia, non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma or lymphoma,
CC myelodysplastic syndromes (MDS), myeloproliferative syndromes (MPS),
CC Waldenstrom's macroglobulinemia or Burkett's lymphoma, immune disorder is
CC chosen from rheumatoid arthritis, systemic lupus erythematosus (SLE),
CC type I diabetes, asthma, atopic dermatitis, allergic rhinitis,
CC thrombocytopenic purpura, multiple sclerosis, psoriasis, Sjogren's
CC syndrome, Hashimoto's thyroiditis, Grave's disease, primary biliary
CC cirrhosis, Wegener's granulomatosis, tuberculosis, and graft versus host
CC disease. The present sequence is a human anti-BCMA antibody heavy chain
CC variable region, used in the invention for treating cancer or immune
CC disorder.
XX
SQ Sequence 121 AA;
Query Match 100.0%; Score 652; Length 121;
Best Local Similarity 100.0%;
Matches 121; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVQSGAEVKKPGASVKLSCKASGYTFTDYYIHWVRQAPGQGLEWIGYINPNSGYTNY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKLSCKASGYTFTDYYIHWVRQAPGQGLEWIGYINPNSGYTNY 60
Qy 61 AQKFQGRATMTADKSINTAYVELSRLRSDDTAVYFCTRYMWERVTGFFDFWGQGTMVTVS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 AQKFQGRATMTADKSINTAYVELSRLRSDDTAVYFCTRYMWERVTGFFDFWGQGTMVTVS 120
Qy 121 S 121
|
Db 121 S 121
RESULT 1 from 8.rag database.
BEG60546
(NOTE: this sequence has 12 duplicates in the database searched.
See complete list at the end of this report)
ID BEG60546 standard; protein; 108 AA.
XX
AC BEG60546;
XX
DT 02-NOV-2017 (first entry)
XX
DE Anti-BCMA antibody light chain variable region, SEQ ID 19.
XX
KW APRIL receptor; B-cell maturation antigen; BCMA protein; CD269;
KW allergic rhinitis; antibody; antibody therapy; asthma; atopic dermatitis;
KW cancer; cytostatic; graft versus host disease; graves disease;
KW hashimotos disease; hematological neoplasm; hodgkins disease;
KW immune disorder; immunomodulator; insulin dependent diabetes; leukemia;
KW light chain variable region; lymphoma; macroglobulinemia;
KW multiple myeloma; multiple sclerosis;
KW mycobacterium tuberculosis infection; myelodysplastic syndrome;
KW myeloproliferative disorder; non-hodgkin lymphoma; pharmaceutical;
KW primary biliary cirrhosis; psoriasis; rheumatoid arthritis;
KW sjoegrens syndrome; systemic lupus erythematosus; therapeutic;
KW thrombocytopenic purpura; wegener granulomatosis.
XX
OS Unidentified.
XX
CC PN US2017233484-A1.
XX
CC PD 17-AUG-2017.
XX
CC PF 16-FEB-2017; 2017US-00434921.
XX
PR 17-FEB-2016; 2016US-0296594P.
PR 16-SEP-2016; 2016US-0396084P.
XX
CC PA (SEGE ) SEATTLE GENETICS INC.
XX
CC PI Sussman D, Ryan M, Westendorf L, Feldhaus M;
XX
DR WPI; 2017-56594M/57.
XX
CC PT New humanized, chimeric or veneered antibody used in pharmaceutical
CC PT composition for treating cancer or immune disorder e.g. multiple myeloma,
CC PT rheumatoid arthritis, and asthma comprises mature heavy and light chain
CC PT variable region.
XX
CC PS Claim 2; SEQ ID NO 19; 88pp; English.
XX
CC The present invention relates to a novel humanized, chimeric or veneered
CC antibody useful for treating cancer or immune disorder. The invention
CC cancer is chosen from multiple myeloma, hematological cancer, myeloma,
CC leukemia, non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma or lymphoma,
CC myelodysplastic syndromes (MDS), myeloproliferative syndromes (MPS),
CC Waldenstrom's macroglobulinemia or Burkett's lymphoma, immune disorder is
CC chosen from rheumatoid arthritis, systemic lupus erythematosus (SLE),
CC type I diabetes, asthma, atopic dermatitis, allergic rhinitis,
CC thrombocytopenic purpura, multiple sclerosis, psoriasis, Sjogren's
CC syndrome, Hashimoto's thyroiditis, Grave's disease, primary biliary
CC cirrhosis, Wegener's granulomatosis, tuberculosis, and graft versus host
CC disease. The present sequence is an anti-BCMA antibody light chain
CC variable region, used in the invention for treating cancer or immune
CC disorder.
XX
SQ Sequence 108 AA;
Query Match 100.0%; Score 559; Length 108;
Best Local Similarity 100.0%;
Matches 108; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSVSASVGDRVTITCLASEDISDDLAWYQQKPGKAPKVLVYTTSSLQSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSVSASVGDRVTITCLASEDISDDLAWYQQKPGKAPKVLVYTTSSLQSGVPS 60
Qy 61 RFSGSGSGTDFTLTISSLQPEDFATYFCQQTYKFPPTFGGGTKVEIKR 108
||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDFATYFCQQTYKFPPTFGGGTKVEIKR 108
11. Claim(s) 121 and 122 is/are rejected under 35 U.S.C. 103 as being unpatentable over Sussman et al., US2017233484 (published August 17, 2017), and further in view of Aardalen et al., WO 2020/261093 A1 (effectively filed 22 June 2020). Sussman teaches B cell maturation antigen (BCMA) antibody or antigen-binding fragment thereof, comprises a heavy chain variable region comprising a CDR1 comprising SEQ ID NO: 1, a CDR2 comprising SEQ ID NO: 2, and a CDR3 comprising SEQ ID NO: 3, and a light chain variable domain comprising a CDR1 comprising SEQ ID NO: 5, a CDR2 comprising SEQ ID NO: 6, and a CDR3 comprising SEQ ID NO: 7, see sequence alignments.
“Compositions or methods “comprising” one or more recited elements may include other elements not specifically recited. For example, a composition that comprises antibody may contain the antibody alone or in combination with other ingredients.”, see page 5, section 0055. A pharmaceutically compatible ingredient including a pharmaceutically acceptable diluent, adjuvant, excipient, or vehicle is combined with which an anti-BCMA antibody, see page 6, sections 0064 and 0065.
Dosages comprising anti-BCMA antibodies alone or as drug-conjugates thereof are administered, see VII. spanning pages 17 and 18.
The anti-BCMA antibodies disclosed herein “…can be provided in the form of kit with all the necessary reagents…, see page 19, section 0174.
Sussman does not teach the pharmaceutical composition comprising said BCMA antibody or antigen-binding fragment thereof cited in the claims in combination with nirogacestat and/or dexamethasone.
However, Aardalen discloses administering a B cell maturation antigen (BCMA) binding molecule with a second therapeutic agent, wherein “the BCMA binding molecule and the second therapeutic agent are administered simultaneously, separately, or over a period of time” for the treatment of multiple myeloma (MM), see page 4, lines 25-29; page 7, lines 28-32; page 37, lines 14-19; and page 47, lines 4-8.
“[T]he second therapeutic agent is a gamma secretase inhibitor (GSI),” including PF-3084014, see page 4, line 30; page 38, lines 1-6; page 40. PF-3084014 is art known as “…nirogacestat or (S)-2-(((S)-6,8-difluoro-1,2,3,4-tetrahydronaphthalen-2-yl)amino )-N-(1-(2-methyl-1-(neopentylamino )propan-2-yl)-1 H-imidazol-4-yl)pentanamide, or a pharmaceutically acceptable salt thereof.”, see page 40, lines 9-15; page 48, line 11; .
Moreover, although the claims recite a kit and a container for use, no positive recitation of the kit ingredients/elements distinguishes the claim over the reference. Therefore, the reference reads on the claimed kit and container of use. It is noted that kits traditionally include structurally material such as instructions, labeling and promotional material. Textural instructions are given little patentable weight because a piece of paper is only relevant to the claimed invention if it is functionally tied to the structure of the invention, for example, demarcations on a measuring cup or slide rule. The instructions included on the piece of paper are viewed as a recitation of intended use and therefore are not given patentable weight in comparing the claim with the prior art. See MPEP 706.03(a). Thus, the instructions for use included in a kit or article of manufacture constitutes an “intended use” for that kit or article of manufacture. Thus, the claimed subject matter is considered obvious over the prior art, absent sufficient factual evidence to the contrary.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to contain therapeutic antibodies for the treatment of multiple myeloma in a kit with instructions. One of ordinary skill in the art would have been
motivated to make a kit because test kits including compounds are packaged for the advantages of convenience and economy for the ordinarily skilled artisan or the practitioner. Kits are conveniently made to reproducibly obtain results under test conditions and it is conventional to assemble necessary reagents including compounds, such as antibodies for the effective treatment for the convenience of the practitioner and commercial expediency.
RESULT 1 from 1fus2fus3.align450.rag database.
BEG60540
(NOTE: this sequence has 27 duplicates in the database searched.
See complete list at the end of this report)
ID BEG60540 standard; protein; 121 AA.
XX
AC BEG60540;
XX
DT 02-NOV-2017 (first entry)
XX
DE Human anti-BCMA antibody heavy chain variable region, SEQ ID 13.
XX
KW APRIL receptor; B-cell maturation antigen; BCMA protein; CD269;
KW allergic rhinitis; antibody; antibody therapy; asthma; atopic dermatitis;
KW cancer; cytostatic; graft versus host disease; graves disease;
KW hashimotos disease; heavy chain variable region; hematological neoplasm;
KW hodgkins disease; immune disorder; immunomodulator;
KW insulin dependent diabetes; leukemia; lymphoma; macroglobulinemia;
KW multiple myeloma; multiple sclerosis;
KW mycobacterium tuberculosis infection; myelodysplastic syndrome;
KW myeloproliferative disorder; non-hodgkin lymphoma; pharmaceutical;
KW primary biliary cirrhosis; psoriasis; rheumatoid arthritis;
KW sjoegrens syndrome; systemic lupus erythematosus; therapeutic;
KW thrombocytopenic purpura; wegener granulomatosis.
XX
OS Homo sapiens.
XX
CC PN US2017233484-A1.
XX
CC PD 17-AUG-2017.
XX
CC PF 16-FEB-2017; 2017US-00434921.
XX
PR 17-FEB-2016; 2016US-0296594P.
PR 16-SEP-2016; 2016US-0396084P.
XX
CC PA (SEGE ) SEATTLE GENETICS INC.
XX
CC PI Sussman D, Ryan M, Westendorf L, Feldhaus M;
XX
DR WPI; 2017-56594M/57.
XX
CC PT New humanized, chimeric or veneered antibody used in pharmaceutical
CC PT composition for treating cancer or immune disorder e.g. multiple myeloma,
CC PT rheumatoid arthritis, and asthma comprises mature heavy and light chain
CC PT variable region.
XX
CC PS Claim 2; SEQ ID NO 13; 88pp; English.
XX
CC The present invention relates to a novel humanized, chimeric or veneered
CC antibody useful for treating cancer or immune disorder. The invention
CC cancer is chosen from multiple myeloma, hematological cancer, myeloma,
CC leukemia, non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma or lymphoma,
CC myelodysplastic syndromes (MDS), myeloproliferative syndromes (MPS),
CC Waldenstrom's macroglobulinemia or Burkett's lymphoma, immune disorder is
CC chosen from rheumatoid arthritis, systemic lupus erythematosus (SLE),
CC type I diabetes, asthma, atopic dermatitis, allergic rhinitis,
CC thrombocytopenic purpura, multiple sclerosis, psoriasis, Sjogren's
CC syndrome, Hashimoto's thyroiditis, Grave's disease, primary biliary
CC cirrhosis, Wegener's granulomatosis, tuberculosis, and graft versus host
CC disease. The present sequence is a human anti-BCMA antibody heavy chain
CC variable region, used in the invention for treating cancer or immune
CC disorder.
XX
SQ Sequence 121 AA;
Query Match 87.7%; Score 175.4; Length 121;
Best Local Similarity 42.5%;
Matches 34; Conservative 0; Mismatches 0; Indels 46; Gaps 2;
Qy 1 DYYIH--------------YINPNSGYTNYAQKFQG------------------------ 22
||||| |||||||||||||||||
Db 31 DYYIHWVRQAPGQGLEWIGYINPNSGYTNYAQKFQGRATMTADKSINTAYVELSRLRSDD 90
Qy 23 --------YMWERVTGFFDF 34
||||||||||||
Db 91 TAVYFCTRYMWERVTGFFDF 110
RESULT 2 from 5fus6fus7.align450.rag database.
BEG60546
(NOTE: this sequence has 12 duplicates in the database searched.
See complete list at the end of this report)
ID BEG60546 standard; protein; 108 AA.
XX
AC BEG60546;
XX
DT 02-NOV-2017 (first entry)
XX
DE Anti-BCMA antibody light chain variable region, SEQ ID 19.
XX
KW APRIL receptor; B-cell maturation antigen; BCMA protein; CD269;
KW allergic rhinitis; antibody; antibody therapy; asthma; atopic dermatitis;
KW cancer; cytostatic; graft versus host disease; graves disease;
KW hashimotos disease; hematological neoplasm; hodgkins disease;
KW immune disorder; immunomodulator; insulin dependent diabetes; leukemia;
KW light chain variable region; lymphoma; macroglobulinemia;
KW multiple myeloma; multiple sclerosis;
KW mycobacterium tuberculosis infection; myelodysplastic syndrome;
KW myeloproliferative disorder; non-hodgkin lymphoma; pharmaceutical;
KW primary biliary cirrhosis; psoriasis; rheumatoid arthritis;
KW sjoegrens syndrome; systemic lupus erythematosus; therapeutic;
KW thrombocytopenic purpura; wegener granulomatosis.
XX
OS Unidentified.
XX
CC PN US2017233484-A1.
XX
CC PD 17-AUG-2017.
XX
CC PF 16-FEB-2017; 2017US-00434921.
XX
PR 17-FEB-2016; 2016US-0296594P.
PR 16-SEP-2016; 2016US-0396084P.
XX
CC PA (SEGE ) SEATTLE GENETICS INC.
XX
CC PI Sussman D, Ryan M, Westendorf L, Feldhaus M;
XX
DR WPI; 2017-56594M/57.
XX
CC PT New humanized, chimeric or veneered antibody used in pharmaceutical
CC PT composition for treating cancer or immune disorder e.g. multiple myeloma,
CC PT rheumatoid arthritis, and asthma comprises mature heavy and light chain
CC PT variable region.
XX
CC PS Claim 2; SEQ ID NO 19; 88pp; English.
XX
CC The present invention relates to a novel humanized, chimeric or veneered
CC antibody useful for treating cancer or immune disorder. The invention
CC cancer is chosen from multiple myeloma, hematological cancer, myeloma,
CC leukemia, non-Hodgkin's lymphoma (NHL) or Hodgkin's lymphoma or lymphoma,
CC myelodysplastic syndromes (MDS), myeloproliferative syndromes (MPS),
CC Waldenstrom's macroglobulinemia or Burkett's lymphoma, immune disorder is
CC chosen from rheumatoid arthritis, systemic lupus erythematosus (SLE),
CC type I diabetes, asthma, atopic dermatitis, allergic rhinitis,
CC thrombocytopenic purpura, multiple sclerosis, psoriasis, Sjogren's
CC syndrome, Hashimoto's thyroiditis, Grave's disease, primary biliary
CC cirrhosis, Wegener's granulomatosis, tuberculosis, and graft versus host
CC disease. The present sequence is an anti-BCMA antibody light chain
CC variable region, used in the invention for treating cancer or immune
CC disorder.
XX
SQ Sequence 108 AA;
Query Match 81.6%; Score 109.3; Length 108;
Best Local Similarity 36.5%;
Matches 27; Conservative 0; Mismatches 0; Indels 47; Gaps 2;
Qy 1 LASEDISDDLA---------------TTSSLQS--------------------------- 18
||||||||||| |||||||
Db 24 LASEDISDDLAWYQQKPGKAPKVLVYTTSSLQSGVPSRFSGSGSGTDFTLTISSLQPEDF 83
Qy 19 -----QQTYKFPPT 27
|||||||||
Db 84 ATYFCQQTYKFPPT 97
Conclusion
12. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however she can generally be reached 8AM-8PM, Monday through Friday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the Examiner by telephone are unsuccessful, the Examiner’s supervisor, Julie Wu can be reached on 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
31 August 2026
/Alana Harris Dent/Primary Examiner, Art Unit 1643
Prosecution Insights