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 1-7, 9, 13-16, 20-23, 28, 31, 38 and 40 are pending.
Claims 8, 10-12, 17-19, 24-27, 29, 30, 32-37 and 39 have been cancelled.
Claims 3, 4, 9, 13-21, 28, 38 and 40 have been amended.
Claims 1-7, 9, 13-16, 20-23, 28, 31, 38 and 40 are examined on the merits.
Claim Objections
3. Claim 1 is objected to because of the following informality: the verb, administrating is not between the terms, comprising and one on line 2 of the claim.
Correction is required.
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 4-7, 9 and 13-19 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 claims are drawn to a method for treating small cell lung cancer (SCLC) comprising rounds of induction therapy and optionally, maintenance therapy, wherein a round of each comprises anti-fucosyl-GM1, wherein the anti-fucosyl-GM1 antibody cross competes with BMS-986012 for binding to fucosyl-GM1. The BMS-986012 comprises heavy and light chain variable regions comprising the sequences of SEQ ID NOs: 1 and 2, respectively. The instant claims read on antibodies requiring a specific function without a correlation to structure which can affect antigen binding as well as therapeutic function.
The MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through 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 applicant was in possession of the claimed genus. A “representative number of species” means that the species which are adequately described are representative of the entire genus. See, e.g., AbbVie Deutschland GMBH v. Janssen Biotech, 759 F.3d 1285, 111 USPQ2d 1780 (Fed. Cir. 2014). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species. The “structural features common to the members of the genus” needed for one of skill in the art to ‘visualize or recognize’ the members of the genus take into account the state of the art at the time of the invention. “Functional” terminology may be used “when the art has established a correlation between structure and function” but “merely drawing a fence around the outer limits of a purported genus is not an adequate substitute for describing a variety of materials constituting the genus and showing one has invented a genus and not just a species.” Ariad Pharmaceuticals Inc. v. Eli Lilly & Co., 598 F3d 1336, 94 USPQ2d 1161, 1171 (Fed Cir. 2010).
As was well-known in the antibody art, antibodies as a class share an overall structure generally comprising two heavy chain polypeptides that each comprises a heavy chain variable region (VH) and a heavy chain constant region made up of several domains (CH1, hinge, CH2, CH3, and for some antibodies, a CH4). Each of the heavy chains pairs with a light chain polypeptide that comprises a light chain variable region (VL) and a constant region. But while this overall structure is shared amongst antibodies from a wide variety of sources (human, rat, mouse, rabbit), the structure each antibody uses to bind its particular epitope on an antigen is structurally distinct and is formed by a recombination event that results in high variability at the amino acid sequence level. By the time the invention was made, it was well established in the art that the formation of an intact antigen-binding site in an antibody usually required 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, see Section 3
“Antibody Structure and the Antigen Binding Site” and Figure 1 within Almagro et al. (Frontiers in Bioscience 13: 1619-1633, January 1, 2008). Chimeric antibodies comprise the heavy and light chain variable regions of a rodent antibody linked to human constant regions and preserve the entirety of the VH and VL of the parent antibody. Id. at 1619-20. Humanized antibodies comprise only the CDRs, or in some cases an abbreviated subset of residues within the CDRs, of a parental rodent antibody in the context of human framework sequences. Id. at Section 4. All of the CDRs of the heavy and light chain, in their proper order of CDR1, then 2, then 3, and in the context of framework sequences which maintain their required conformation are generally required to produce a humanized antibody in which the heavy and light chains associate to form an antigen-binding region that binds the same antigen as the parental rodent antibody. Id. at Section 4. Almagro provides a detailed discussion regarding various methods of humanization, including rationale design approaches and empirical approaches based on random screening, see Almagro, Sections 4 and 5.
Overall, at the time the invention was made, the level of skill for preparing antibodies and then selecting those antibodies with desired functional properties was high. However, even if a selection procedure was, at the time of the invention, sufficient to enable the skilled artisan to identify antibodies with the recited functional properties, the written description provision of 35 U.S.C § 112 is severable from its enablement provision. Ariad Pharm., Inc. v. Eli Lilly & Co., 598 F.3d 1336 (Fed. Cir. 2010); see also Centocor Ortho Biotech Inc. v. Abbott Labs., 97 USPQ2d 1870, 1876 (Fed. Cir. 2011) (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the [7,070,775] patent possessed such an antibody.”) Absent the conserved structure provided by all six CDRs in the context of appropriate VH and VL framework sequences, the skilled artisan generally would not be able to visualize or otherwise predict, a priori, what an antibody with a particular set of functional properties would look like structurally.
MPEP § 2163 states that a “representative number of species” means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The CDR sequences of one antibody do not predict the CDR sequence/structure of any and all other binding variant antibodies yet to be discovered. The instant application does not provide adequate written description for any and all antibodies which function as claimed having less than all 6 CDRs defined and yet to be discovered, even those that bind known epitopes. Furthermore, although screening applications are well known in the art to identify antibodies, screening is only a wish or plan for the future invention of undiscovered, unknown antibodies the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention). Based on the disclosed antibody sequences, one could not readily envision or predict the CDR sequences of any and all other future, undiscovered variant antibodies that can function as claimed. A definition by function does not suffice to define the genus because it is only an indication of what the antibody does, rather than what it is.
A description of a genus of antibodies may be achieved by means of a recitation of a representative number of antibodies, defined by sequence, falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus. The written description requirement can be met by showing that an invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, i.e., complete or partial structure, other physical and/or chemical properties, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics. The court found that if the disclosed species only abide in a corner of the genus, one has not described the genus sufficiently to show that the inventor invented, or had possession of, the genus. He only described a portion of it. The specifically defined antibody sequences claimed or disclosed in the specification are not representative of nor predictive of any and all other antibody sequences for the broadly claimed genus.
Applicants are directed to the recent and relevant decision in AbbVie Deutschland GmbH v. Janssen Biotech, Inc. (Fed. Cir. 2014). The court found that if the disclosed species only abide in a corner of the genus, one has not described the genus sufficiently to show that the inventor invented, or had possession of, the genus. He only described a portion of it. Therefore, claims which do not define the antibodies with 100% identity to specific variable or CDR sequences or do not define all 6 CDR regions or both VH and VL in one claim, are rejected for not adequately providing written description for the entire genus instantly claimed. Furthermore, it is also 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 that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. 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 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 (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 (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).
In the absence of a representative number of species, the written description requirement for a claimed genus may be satisfied by disclosure of relevant, identifying characteristics; i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus. To meet this requirement in the instant case, the specification must describe structural features that convey the claimed cross competing antibody’s activity. As noted above, the art generally accepted that the combination of the CDRs within the VH and VL pair of an antibody were essential for binding specificity. But the specification does not describe what residues within the CDRs confer the binding activity claimed. Accordingly, the skilled artisan would not be able to discern a structure/function correlation for antibodies other than those comprising either all six CDRs (in the context of VH and VL regions) of one parental antibody, or the VH and VL of one parental antibody. Given the lack of shared structural properties that provide the claimed binding activity, the limited number of species described, and the fact that the species that were described cannot be considered representative of the broad genus of competing antibodies, Applicant was not in possession of the invention as claimed. Claims only reciting functional language (other than merely antigen binding) require a sequence structure correlation to meet the written description requirements.
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) 22 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chu et al., (Annals of Oncology 28 (Supplement 5: v539-v542, 2017/ IDS reference 3C submitted April 18, 2024). Chu discloses [patients] “[p]ts with [small cell lung cancer] SCLC who relapsed after or were refractory to first-line therapy received BMS-986012 400 or 1000 mg + nivolumab 360 mg IV [21 days long] Q3W”, see Methods. Absent evidence to the contrary, both antibodies were administered on the same day Q3W.
“BMS986012 is a first-in-class, fully human [monoclonal antibody] mAb with enhanced antibody-dependent cell mediated cytotoxicity that binds to fucosyl-GM1, a ganglioside highly expressed on SCLC. “, see sentence that bridges columns 1 and 2. Nivolumab is an anti-programmed death-1 mAb, see sentence before Methods segment.
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) 1-7, 9, 13-16, 20 and 21 is/are rejected under 35 U.S.C. 103 as being unpatentable over Lopez-Chavez, WO 2019/246557 A1 (published 26 December 2019), and further in view of Cardarelli et al., (WO 2017/181034 A1 published 19 October 2017/ IDS reference 2B submitted April 18, 2024). Lopez-Chavez teaches treating extensive-stage small cell lung cancer (ES-SCLC) administering to the individual a PD-1 axis binding antagonist, carboplatin and etoposide, see abstract. “In particular, the methods and uses are based on data from a randomized Phase III clinical study of atezolizumab…in combination with carboplatin and etoposide in individuals with previously -untreated…(ES-SCLC).”, see page 2, section 0009; section 0014 bridging pages 3 and 4.
“[T]reatment comprises an induction phase and a maintenance phase (or “maintenance therapy”). In some embodiments, the induction phase comprises administering the PD-1 axis binding antagonist (e.g., an anti-PD-Ll antibody such as atezolizumab) at a dose of 1200 mg on Day 1, the platinum agent (e.g., carboplatin or cisplatin) at a dose sufficient to achieve an initial target Area Under the Curve (AUC) of 5 mg/mL/min on Day 1, and the topoisomerase II inhibitor (e.g., etoposide) at a dose of 100 mg/m2 on each of Days 1, 2, and 3 of each 21-day cycle for Cycles 1-4. In some embodiments, the maintenance phase comprises administering the PD-1 axis binding antagonist (e.g., an anti-PD-L1 antibody such as atezolizumab) at a dose of 1200 mg on Day l of each 21-day cycle following Cycle 4.”, see page 75, section 0287.
“During the induction phase, etoposide (100 mg/m2) was also administered intravenously over 60 minutes on Days 2 and 3.”, see page 107, section 0382. And the maintenance phase comprising the PD-1 axis binding antagonist may extend past 21 days, thus reading on one or more 28-day rounds of maintenance therapy, see Table 4 on page 75.
The cycles are equivalent to rounds. Hence, the induction phase for 4 cycles, reads on Applicant’s exactly four rounds for induction therapy. The induction phase last 21 days for each round, see page 30, section 0124; page 75, section 0287; page 99, section 0358.
The PD-1 axis binding antagonist is also an anti-PD-1 antibody including nivolumab, see page 31, sections 0127 and 0128. Lopez-Chavez teaches heavy chain comprising SEQ ID NO: 13 and light chain comprising SEQ ID NO: 14.
Lopez-Chavez does not teach the claimed method, wherein an anti-fucosyl-GM1 antibody comprises a heavy chain variable region (VH) (comprising SEQ ID NO: 1), light chain variable region (VL) (comprising SEQ ID NO: 2), heavy chain (comprising SEQ ID NO: 3) and light chain (comprising SEQ ID NO: 4) is administered with the taught combination at the induction and maintenance phases at the dosages cited in claims 13 and 14. Nor, does Lopez-Chavez teach the anti-PD-1 antibody, nivolumab (comprising heavy chain, SEQ ID NO: 13 and light chain, SEQ ID NO: 14) is administered during induction and maintenance phases at the dosages cited in claims 15, 16 and 21.
However, Cardarelli teaches treating SCLC with the administration of anti-fucosyl-GM1 BMS-986012 antibody with etoposide, see page 4, section 0016; and Example 3 on page 22.
The anti-fucosyl-GM1 antibody contains a VH comprising the sequence of SEQ ID NO: 1 and VL comprising the sequence of SEQ ID NO: 2, as well as a heavy chain comprising the sequence of SEQ ID NO: 3 and light chain containing a light chain comprising the sequence of SEQ ID NO: 4 and non-fucosylated, see sequence summaries and alignments at close of rejection.
“[T]he anti-fucosyl-GMl mAb competes with BMS- 986012, comprises the same CDRs as BMS-986012, comprises the same heavy and light chain variable domains as BMS-986012”, see page 2, section 0006; page 14, section 0055; and segment V. beginning on page 17.
It would have been obvious to one of ordinary skill in the art at the
effective filing date of the claimed invention to combine the therapeutic agents of Lopez-Chavez and Cardarelli to treat ESLC with the combination of carboplatin, etoposide, anti-fucosyl-GM1 and an immune checkpoint inhibitor, as well as arrive at the specific dosages set forth in the claims.
One of ordinary skill in the art would have been motivated to do so
with a reasonable expectation of success by teachings in all the references treating lung cancer with a combinatorial approach, which extends progression free survival (PFS) and overall survival (OS), see both references in their entirety. Notwithstanding, it is art known one of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by teachings well known in the art, that dosages of any pharmaceutical composition must be adjusted and optimized to arrive at the desired result.
BHB92903 from 13.rag database.
ID BHB92903 standard; protein; 440 AA.
XX
AC BHB92903;
XX
DT 20-FEB-2020 (first entry)
XX
DE Anti-PD-L1 antibody heavy chain, SEQ ID 11.
XX
KW PD-L1 protein; antibody; antibody therapy; cytostatic; enzyme inhibition;
KW heavy chain; lung tumor; metastasis; metastatic lung cancer;
KW respiratory-gen.; small-cell lung cancer; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2019246557-A1.
XX
CC PD 26-DEC-2019.
XX
CC PF 21-JUN-2019; 2019WO-US038534.
XX
PR 23-JUN-2018; 2018US-0689105P.
PR 17-AUG-2018; 2018US-0719461P.
PR 25-SEP-2018; 2018US-0736326P.
XX
CC PA (GETH ) GENENTECH INC.
XX
CC PI Lopez-Chavez A;
XX
DR WPI; 2019-A8465F/007.
XX
CC PT Treating individual having lung cancer by administering to individual,
CC PT anti-programmed cell death ligand (PD-L)1 antibody, platinum agent (e.g.
CC PT carboplatin), and topoisomerase II inhibitor (e.g. etoposide).
XX
CC PS Disclosure; SEQ ID NO 11; 146pp; English.
XX
CC The present invention relates to a novel method for treating an
CC individual having lung cancer. The method involves administering an anti-
CC PD-L1 antibody, a platinum agent and a topoisomerase II inhibitor,
CC wherein the treatment extends the progression free survival (PFS) of the
CC individual. The invention also provides: a method for treating an
CC individual having extensive-stage small cell lung cancer (ES-SCLC); a kit
CC (k1) comprising the anti-PD-L1 antibody for use in combination with the
CC platinum agent and topoisomerase II inhibitor; and a kit (k2) comprising
CC atezolizumab for use in combination with carboplatin and etoposide for
CC treating an individual having lung cancer. The lung cancer or ES-SCLC can
CC be metastasized to the brain, liver, lymph nodes, or adrenal gland.
XX
SQ Sequence 440 AA;
BHB92904 from 14.rag database.
ID BHB92904 standard; protein; 214 AA.
XX
AC BHB92904;
XX
DT 20-FEB-2020 (first entry)
XX
DE Anti-PD-L1 antibody light chain, SEQ ID 12.
XX
KW PD-L1 protein; antibody; antibody therapy; cytostatic; enzyme inhibition;
KW light chain; lung tumor; metastasis; metastatic lung cancer;
KW respiratory-gen.; small-cell lung cancer; therapeutic.
XX
OS Unidentified.
XX
CC PN WO2019246557-A1.
XX
CC PD 26-DEC-2019.
XX
CC PF 21-JUN-2019; 2019WO-US038534.
XX
PR 23-JUN-2018; 2018US-0689105P.
PR 17-AUG-2018; 2018US-0719461P.
PR 25-SEP-2018; 2018US-0736326P.
XX
CC PA (GETH ) GENENTECH INC.
XX
CC PI Lopez-Chavez A;
XX
DR WPI; 2019-A8465F/007.
XX
CC PT Treating individual having lung cancer by administering to individual,
CC PT anti-programmed cell death ligand (PD-L)1 antibody, platinum agent (e.g.
CC PT carboplatin), and topoisomerase II inhibitor (e.g. etoposide).
XX
CC PS Disclosure; SEQ ID NO 12; 146pp; English.
XX
CC The present invention relates to a novel method for treating an
CC individual having lung cancer. The method involves administering an anti-
CC PD-L1 antibody, a platinum agent and a topoisomerase II inhibitor,
CC wherein the treatment extends the progression free survival (PFS) of the
CC individual. The invention also provides: a method for treating an
CC individual having extensive-stage small cell lung cancer (ES-SCLC); a kit
CC (k1) comprising the anti-PD-L1 antibody for use in combination with the
CC platinum agent and topoisomerase II inhibitor; and a kit (k2) comprising
CC atezolizumab for use in combination with carboplatin and etoposide for
CC treating an individual having lung cancer. The lung cancer or ES-SCLC can
CC be metastasized to the brain, liver, lymph nodes, or adrenal gland.
XX
SQ Sequence 214 AA;
RESULT 15 from 1.rag database including underlined CDRHs 5-7.
BEM82341
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BEM82341 standard; protein; 451 AA.
XX
AC BEM82341;
XX
DT 14-DEC-2017 (first entry)
XX
DE Anti-FucGM1 antibody heavy chain, SEQ ID 3.
XX
KW FucGM1 protein; antibody; antibody therapy; cancer; cytostatic;
KW heavy chain; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2017181034-A1.
XX
CC PD 19-OCT-2017.
XX
CC PF 14-APR-2017; 2017WO-US027663.
XX
PR 14-APR-2016; 2016US-0322407P.
XX
CC PA (BRIM ) BRISTOL-MYERS SQUIBB CO.
XX
CC PI Cardarelli JM, Chen B, Lopes De Menezes DE, Pan C, Ponath PD;
XX
DR WPI; 2017-71604F/74.
XX
CC PT Treating subject afflicted with cancer involves administering to subject
CC PT therapeutically effective combination of anti-fucosyl GMl antibody, or
CC PT their antigen-binding portion and anti-CD 137 antibody, or their antigen-
CC PT binding portion.
XX
CC PS Claim 5; SEQ ID NO 3; 33pp; English.
XX
CC The present invention relates to a novel method for treating a subject
CC afflicted with cancer. The method involves: administering to the subject
CC a therapeutically effective combination of: (a) an anti-fucosyl GM1
CC antibody, or an antigen-binding portion thereof; and (b) an anti-CD137
CC antibody, or its antigen-binding portion. The method enables to treat
CC subject afflicted with cancer provides fucosyl-GMl as highly specific
CC tumor antigen, which may be targeted by an immunotherapeutic in effective
CC manner. The present sequence is an anti-FucGM1 antibody heavy chain,
CC where the antibody is used in the invention for treating a subject
CC afflicted with cancer.
XX
SQ Sequence 451 AA;
Query Match 100.0%; Score 645; Length 451;
Best Local Similarity 100.0%;
Matches 122; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGSVQPGESLRLSCVASGFTFSRYKMNWVRQAPGKGLEWVSYISRSGRDIYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGSVQPGESLRLSCVASGFTFSRYKMNWVRQAPGKGLEWVSYISRSGRDIYY 60
Qy 61 ADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCAGTVTTYYYDFGMDVWGQGTTVTV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCAGTVTTYYYDFGMDVWGQGTTVTV 120
Qy 121 SS 122
||
Db 121 SS 122
BEM82340 from 2.rag database include CDRLs, SEQ ID Nos. 8-10.
ID BEM82340 standard; protein; 107 AA.
XX
AC BEM82340;
XX
DT 14-DEC-2017 (first entry)
XX
DE Anti-FucGM1 antibody VL region, SEQ ID 2.
XX
KW FucGM1 protein; antibody; antibody therapy; cancer; cytostatic;
KW light chain variable region; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2017181034-A1.
XX
CC PD 19-OCT-2017.
XX
CC PF 14-APR-2017; 2017WO-US027663.
XX
PR 14-APR-2016; 2016US-0322407P.
XX
CC PA (BRIM ) BRISTOL-MYERS SQUIBB CO.
XX
CC PI Cardarelli JM, Chen B, Lopes De Menezes DE, Pan C, Ponath PD;
XX
DR WPI; 2017-71604F/74.
XX
CC PT Treating subject afflicted with cancer involves administering to subject
CC PT therapeutically effective combination of anti-fucosyl GMl antibody, or
CC PT their antigen-binding portion and anti-CD 137 antibody, or their antigen-
CC PT binding portion.
XX
CC PS Claim 7; SEQ ID NO 2; 33pp; English.
XX
CC The present invention relates to a novel method for treating a subject
CC afflicted with cancer. The method involves: administering to the subject
CC a therapeutically effective combination of: (a) an anti-fucosyl GM1
CC antibody, or an antigen-binding portion thereof; and (b) an anti-CD137
CC antibody, or its antigen-binding portion. The method enables to treat
CC subject afflicted with cancer provides fucosyl-GMl as highly specific
CC tumor antigen, which may be targeted by an immunotherapeutic in effective
CC manner. The present sequence is an anti-FucGM1 antibody light chain
CC variable region, where the antibody is used in the invention for treating
CC a subject afflicted with cancer.
XX
SQ Sequence 107 AA;
RESULT 1 from 3.rag database.
BEM82341
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BEM82341 standard; protein; 451 AA.
XX
AC BEM82341;
XX
DT 14-DEC-2017 (first entry)
XX
DE Anti-FucGM1 antibody heavy chain, SEQ ID 3.
XX
KW FucGM1 protein; antibody; antibody therapy; cancer; cytostatic;
KW heavy chain; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2017181034-A1.
XX
CC PD 19-OCT-2017.
XX
CC PF 14-APR-2017; 2017WO-US027663.
XX
PR 14-APR-2016; 2016US-0322407P.
XX
CC PA (BRIM ) BRISTOL-MYERS SQUIBB CO.
XX
CC PI Cardarelli JM, Chen B, Lopes De Menezes DE, Pan C, Ponath PD;
XX
DR WPI; 2017-71604F/74.
XX
CC PT Treating subject afflicted with cancer involves administering to subject
CC PT therapeutically effective combination of anti-fucosyl GMl antibody, or
CC PT their antigen-binding portion and anti-CD 137 antibody, or their antigen-
CC PT binding portion.
XX
CC PS Claim 5; SEQ ID NO 3; 33pp; English.
XX
CC The present invention relates to a novel method for treating a subject
CC afflicted with cancer. The method involves: administering to the subject
CC a therapeutically effective combination of: (a) an anti-fucosyl GM1
CC antibody, or an antigen-binding portion thereof; and (b) an anti-CD137
CC antibody, or its antigen-binding portion. The method enables to treat
CC subject afflicted with cancer provides fucosyl-GMl as highly specific
CC tumor antigen, which may be targeted by an immunotherapeutic in effective
CC manner. The present sequence is an anti-FucGM1 antibody heavy chain,
CC where the antibody is used in the invention for treating a subject
CC afflicted with cancer.
XX
SQ Sequence 451 AA;
Query Match 100.0%; Score 2407; Length 451;
Best Local Similarity 100.0%;
Matches 451; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGSVQPGESLRLSCVASGFTFSRYKMNWVRQAPGKGLEWVSYISRSGRDIYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGSVQPGESLRLSCVASGFTFSRYKMNWVRQAPGKGLEWVSYISRSGRDIYY 60
Qy 61 ADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCAGTVTTYYYDFGMDVWGQGTTVTV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCAGTVTTYYYDFGMDVWGQGTTVTV 120
Qy 121 SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ 180
Qy 181 SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELL 240
Qy 241 GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ 300
Qy 301 YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR 360
Qy 361 EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS 420
Qy 421 RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 451
|||||||||||||||||||||||||||||||
Db 421 RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 451
BEM82342 from 4.rag database.
ID BEM82342 standard; protein; 214 AA.
XX
AC BEM82342;
XX
DT 14-DEC-2017 (first entry)
XX
DE Anti-FucGM1 antibody light chain, SEQ ID 4.
XX
KW FucGM1 protein; antibody; antibody therapy; cancer; cytostatic;
KW light chain; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2017181034-A1.
XX
CC PD 19-OCT-2017.
XX
CC PF 14-APR-2017; 2017WO-US027663.
XX
PR 14-APR-2016; 2016US-0322407P.
XX
CC PA (BRIM ) BRISTOL-MYERS SQUIBB CO.
XX
CC PI Cardarelli JM, Chen B, Lopes De Menezes DE, Pan C, Ponath PD;
XX
DR WPI; 2017-71604F/74.
XX
CC PT Treating subject afflicted with cancer involves administering to subject
CC PT therapeutically effective combination of anti-fucosyl GMl antibody, or
CC PT their antigen-binding portion and anti-CD 137 antibody, or their antigen-
CC PT binding portion.
XX
CC PS Claim 5; SEQ ID NO 4; 33pp; English.
XX
CC The present invention relates to a novel method for treating a subject
CC afflicted with cancer. The method involves: administering to the subject
CC a therapeutically effective combination of: (a) an anti-fucosyl GM1
CC antibody, or an antigen-binding portion thereof; and (b) an anti-CD137
CC antibody, or its antigen-binding portion. The method enables to treat
CC subject afflicted with cancer provides fucosyl-GMl as highly specific
CC tumor antigen, which may be targeted by an immunotherapeutic in effective
CC manner. The present sequence is an anti-FucGM1 antibody light chain,
CC where the antibody is used in the invention for treating a subject
CC afflicted with cancer.
XX
SQ Sequence 214 AA;
10. Claim(s) 22, 23, 28, 31, 38 and 40 is/are rejected under 35 U.S.C. 103 as being unpatentable over Chu et al., (Annals of Oncology 28 (Supplement 5: v539-v542, 2017/ IDS reference 3C submitted April 18, 2024), and further in view of Vangsted et al. (Cancer Research 51: 2879-2884, June 1, 1991), Cardarelli et al., (WO 2017/181034 A1 published 19 October 2017/ IDS reference 2B submitted April 18, 2024) and Cardarelli, J.M., WO 2016/201425 (published 15 December 2016) further referenced herein, Bristol-Myers Squibb Company. Chu teaches [patients] “[p]ts with [small cell lung cancer] SCLC who relapsed after or were refractory to first-line therapy received BMS-986012 400 or 1000 mg + nivolumab 360 mg IV [21 days long] Q3W”, see Methods. Absent evidence to the contrary, both antibodies were administered on the same day Q3W.
“BMS986012 is a first-in-class, fully human [monoclonal antibody] mAb with enhanced antibody-dependent cell mediated cytotoxicity that binds to fucosyl-GM1, a ganglioside highly expressed on SCLC. “, see sentence that bridges columns 1 and 2. Nivolumab is an anti-programmed death-1 mAb, see sentence before Methods segment. BMS986012 is art known to be non-fucosylated (lacking fucosylation on the Fc domain).
Chu does not explicitly teach the patient is afflicted with extensive-stage small cell lung cancer (ES-SCLC). Chu does not teach the anti-fucosyl-GM1 antibody comprises heavy chain comprising SEQ ID NO: 3 and a light chain comprising SEQ ID NO: 4, wherein the anti-fucosyl-GM1 antibody is non-fucosylated and administered on the same day Q4W.
Chu does not teach the anti-PD-1 antibody comprises heavy chain, SEQ ID NO: 13 and light chain comprises, SEQ ID NO: 14 and administered at 480 mg administered on the same day Q4W, nor the administration of an anti-PD-L1 antibody administered at a dose of 1200 mg.
However, Vangsted teaches patients with disseminated cancer involving metastases to other organ sites with FucGM1-positive serum samples and large tumor load are regarded as having extensive disease, see Abstract on page 2879; and page 2883, last sentence before 1st full paragraph (para.)
Cardarelli teaches the anti-fucosyl-GM1 antibody that is BMS-986012 containing a heavy chain comprising the sequence of SEQ ID NO: 3 and light chain containing a light chain comprising the sequence of SEQ ID NO: 4 and non-fucosylated, see page 2, section 0005; page 4, section 0018; page 6, section 0024 and sequence summary. “[T]he anti-Fucosyl-GM1 antibody is administered at a dose ranging from 10 to 2000 mg once every 1, 2, 3 or 4 weeks… the antibody is administered on Days 1, 22, 43, and 64.”, see page 3, section 0010; and page 19, section 0071.
Furthermore, Bristol-Myers Squibb Co. teaches the administration of an antibody or antigen-binding portion thereof that binds specifically to programmed death ligand (PD-L1) or to programed death-1 (PD-1) that is nivolumab containing a heavy chain comprising the sequence of SEQ ID NO: 13 and light chain containing a light chain comprising the sequence of SEQ ID NO: 14, see page 2, lines 13-33; page 11, lines 17-28; page 14, lines 19-21; page 15, line 8-page 21, line 21; page 18, lines 9-31; and sequence summary. Administration of the antibody can occur once every 3 weeks, once every 4 weeks at a fixed or flat dose ranging from about 50-2000 mg, see para. bridging pages 39 and 40.
It would have been obvious to one of ordinary skill in the art at the
effective filing date of the claimed invention to conclude the SCLC of Chu is an ES-SCLC due to its high expression of the gangloside, fucosyl-GM1.
One of ordinary skill in the art would have been motivated to conclude with a reasonable expectation of success by teachings in both references, the SCLC of Chu is an ES-SCLC based on the increased frequency of expression of fucosyl-GM1.
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 Chu BMS-986012 antibody with the anti-fucosyl-GM1 antibody of Cardarelli with known structure given it has successfully targeted the fucosyl-GM1 antigen, as well as substitute the nivolumab antibody of Chu with the known PD-1 antibody of BMS because it too has successfully targeted it receptor and administer both on same day Q4W with nivolumab at 480 mg.
One of ordinary skill in the art would have been motivated to do so
with a reasonable expectation of success by teachings in the secondary references that the targets of the antibodies with known CDRs are art recognized as a plausible alternative and in particular BMS teaches a dosage range that reads on 480 mg. Notwithstanding, it is art known one of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success by teachings well known in the art, that dosages of any pharmaceutical composition must be adjusted and optimized to arrive at the desired result.
RESULT 1 from 3.rag database.
BEM82341
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BEM82341 standard; protein; 451 AA.
XX
AC BEM82341;
XX
DT 14-DEC-2017 (first entry)
XX
DE Anti-FucGM1 antibody heavy chain, SEQ ID 3.
XX
KW FucGM1 protein; antibody; antibody therapy; cancer; cytostatic;
KW heavy chain; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2017181034-A1.
XX
CC PD 19-OCT-2017.
XX
CC PF 14-APR-2017; 2017WO-US027663.
XX
PR 14-APR-2016; 2016US-0322407P.
XX
CC PA (BRIM ) BRISTOL-MYERS SQUIBB CO.
XX
CC PI Cardarelli JM, Chen B, Lopes De Menezes DE, Pan C, Ponath PD;
XX
DR WPI; 2017-71604F/74.
XX
CC PT Treating subject afflicted with cancer involves administering to subject
CC PT therapeutically effective combination of anti-fucosyl GMl antibody, or
CC PT their antigen-binding portion and anti-CD 137 antibody, or their antigen-
CC PT binding portion.
XX
CC PS Claim 5; SEQ ID NO 3; 33pp; English.
XX
CC The present invention relates to a novel method for treating a subject
CC afflicted with cancer. The method involves: administering to the subject
CC a therapeutically effective combination of: (a) an anti-fucosyl GM1
CC antibody, or an antigen-binding portion thereof; and (b) an anti-CD137
CC antibody, or its antigen-binding portion. The method enables to treat
CC subject afflicted with cancer provides fucosyl-GMl as highly specific
CC tumor antigen, which may be targeted by an immunotherapeutic in effective
CC manner. The present sequence is an anti-FucGM1 antibody heavy chain,
CC where the antibody is used in the invention for treating a subject
CC afflicted with cancer.
XX
SQ Sequence 451 AA;
Query Match 100.0%; Score 2407; Length 451;
Best Local Similarity 100.0%;
Matches 451; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGSVQPGESLRLSCVASGFTFSRYKMNWVRQAPGKGLEWVSYISRSGRDIYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGSVQPGESLRLSCVASGFTFSRYKMNWVRQAPGKGLEWVSYISRSGRDIYY 60
Qy 61 ADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCAGTVTTYYYDFGMDVWGQGTTVTV 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISRDNAKNSLYLQMNSLRDEDTAVYYCAGTVTTYYYDFGMDVWGQGTTVTV 120
Qy 121 SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SSASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQ 180
Qy 181 SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELL 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 SSGLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKRVEPKSCDKTHTCPPCPAPELL 240
Qy 241 GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GGPSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQ 300
Qy 301 YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 YNSTYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSR 360
Qy 361 EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 EEMTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKS 420
Qy 421 RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 451
|||||||||||||||||||||||||||||||
Db 421 RWQQGNVFSCSVMHEALHNHYTQKSLSLSPG 451
PNG
media_image1.png
246
1179
media_image1.png
Greyscale
RESULT 106 from 13.rag database.
BDK83374
(NOTE: this sequence has 25 duplicates in the database searched.
See complete list at the end of this report)
ID BDK83374 standard; protein; 439 AA.
XX
AC BDK83374;
XX
DT 09-FEB-2017 (first entry)
XX
DE Anti-PD-1 monoclonal antibody heavy chain, SEQ ID 3.
XX
KW PD-1 protein; antibody therapy; cancer; cytostatic; heavy chain;
KW hematological neoplasm; hepatocellular carcinoma; monoclonal antibody;
KW nivolumab; pancreas tumor; programmed death-1; prophylactic to disease;
KW small-cell lung cancer; solid tumor; therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2016201425-A1.
XX
CC PD 15-DEC-2016.
XX
CC PF 13-JUN-2016; 2016WO-US037207.
XX
PR 12-JUN-2015; 2015US-0174931P.
XX
CC PA (BRIM ) BRISTOL-MYERS SQUIBB CO.
XX
CC PI Cardarelli JM, Clemens WL, Kroog GS, Lopes De Menezes DE, Pan C;
CC PI Ponath PD, Viallet J;
XX
DR WPI; 2016-772421/06.
XX
CC PT Treating cancer comprises administering a combination of an antibody that
CC PT binds to Programmed Death-1 or to Programmed Death Ligand-1 and an
CC PT antibody that binds to C-X-C Chemokine Receptor 4 or to C-X-C motif
CC PT chemokine 12.
XX
CC PS Disclosure; SEQ ID NO 3; 106pp; English.
XX
CC The present invention relates to a novel method for treating a subject
CC afflicted with a cancer. The method involves administering to the subject
CC a combination of an antibody specifically binding to programmed death-1
CC (PD-1) or programmed death ligand-1 (PD-L1), and an antibody specifically
CC binding to C-X-C chemokine receptor 4 (CXCR4) or C-X-C motif chemokine 12
CC (CXCL12). The invention also provides: a method for reducing adverse
CC events in a subject undergoing treatment for cancer; and a kit for
CC treating or preventing a subject afflicted with a cancer, comprising the
CC antibodies. The cancer can be hematological malignancy or solid tumor,
CC wherein the solid tumor is selected from the group consisting of
CC pancreatic cancer (PAC), small cell lung cancer (SCLC) or hepatocellular
CC carcinoma (HCC). The present sequence represents an anti-PD-1 monoclonal
CC antibody nivolumab heavy chain, which is used in preparing the kit of the
CC invention, for treating or preventing the above mentioned cancers in a
CC subject.
XX
SQ Sequence 439 AA;
Query Match 99.8%; Score 2343; Length 439;
Best Local Similarity 100.0%;
Matches 439; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QVQLVESGGGVVQPGRSLRLDCKASGITFSNSGMHWVRQAPGKGLEWVAVIWYDGSKRYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QVQLVESGGGVVQPGRSLRLDCKASGITFSNSGMHWVRQAPGKGLEWVAVIWYDGSKRYY 60
Qy 61 ADSVKGRFTISRDNSKNTLFLQMNSLRAEDTAVYYCATNDDYWGQGTLVTVSSASTKGPS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISRDNSKNTLFLQMNSLRAEDTAVYYCATNDDYWGQGTLVTVSSASTKGPS 120
Qy 121 VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 VFPLAPCSRSTSESTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSSGLYSLSS 180
Qy 181 VVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKP 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 VVTVPSSSLGTKTYTCNVDHKPSNTKVDKRVESKYGPPCPPCPAPEFLGGPSVFLFPPKP 240
Qy 241 KDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 KDTLMISRTPEVTCVVVDVSQEDPEVQFNWYVDGVEVHNAKTKPREEQFNSTYRVVSVLT 300
Qy 301 VLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 VLHQDWLNGKEYKCKVSNKGLPSSIEKTISKAKGQPREPQVYTLPPSQEEMTKNQVSLTC 360
Qy 361 LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 LVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSRLTVDKSRWQEGNVFSCSV 420
Qy 421 MHEALHNHYTQKSLSLSLG 439
|||||||||||||||||||
Db 421 MHEALHNHYTQKSLSLSLG 439
BDK83375 from 14.rag database.
ID BDK83375 standard; protein; 214 AA.
XX
AC BDK83375;
XX
DT 09-FEB-2017 (first entry)
XX
DE Anti-PD-1 monoclonal antibody light chain, SEQ ID 4.
XX
KW PD-1 protein; antibody therapy; cancer; cytostatic;
KW hematological neoplasm; hepatocellular carcinoma; light chain;
KW monoclonal antibody; nivolumab; pancreas tumor; programmed death-1;
KW prophylactic to disease; small-cell lung cancer; solid tumor;
KW therapeutic.
XX
OS Homo sapiens.
XX
CC PN WO2016201425-A1.
XX
CC PD 15-DEC-2016.
XX
CC PF 13-JUN-2016; 2016WO-US037207.
XX
PR 12-JUN-2015; 2015US-0174931P.
XX
CC PA (BRIM ) BRISTOL-MYERS SQUIBB CO.
XX
CC PI Cardarelli JM, Clemens WL, Kroog GS, Lopes De Menezes DE, Pan C;
CC PI Ponath PD, Viallet J;
XX
DR WPI; 2016-772421/06.
XX
CC PT Treating cancer comprises administering a combination of an antibody that
CC PT binds to Programmed Death-1 or to Programmed Death Ligand-1 and an
CC PT antibody that binds to C-X-C Chemokine Receptor 4 or to C-X-C motif
CC PT chemokine 12.
XX
CC PS Disclosure; SEQ ID NO 4; 106pp; English.
XX
CC The present invention relates to a novel method for treating a subject
CC afflicted with a cancer. The method involves administering to the subject
CC a combination of an antibody specifically binding to programmed death-1
CC (PD-1) or programmed death ligand-1 (PD-L1), and an antibody specifically
CC binding to C-X-C chemokine receptor 4 (CXCR4) or C-X-C motif chemokine 12
CC (CXCL12). The invention also provides: a method for reducing adverse
CC events in a subject undergoing treatment for cancer; and a kit for
CC treating or preventing a subject afflicted with a cancer, comprising the
CC antibodies. The cancer can be hematological malignancy or solid tumor,
CC wherein the solid tumor is selected from the group consisting of
CC pancreatic cancer (PAC), small cell lung cancer (SCLC) or hepatocellular
CC carcinoma (HCC). The present sequence represents an anti-PD-1 monoclonal
CC antibody nivolumab light chain, which is used in preparing the kit of the
CC invention, for treating or preventing the above mentioned cancers in a
CC subject.
XX
SQ Sequence 214 AA;
Conclusion
11. 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 at 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
13 February 2026
/Alana Harris Dent/Primary Examiner, Art Unit 1643