DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Priority
This application is a National-Stage entry of PCT/KR2022/001083, filed 1/21/2022. Applicant’s claim for the benefit of a prior-filed foreign application KR10-2021-0010077 filed 1/25/2021, under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
No certified English Language translation of foreign application KR10-2021-0010077 has been provided. In order to perfect the priority claim in regards to intervening art references, as indicated below, a certified translation is required.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 7/24/2023 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Specification
TRADE NAMES, TRADEMARKS, AND OTHER MARKS USED IN COMMERCE:
The use of the terms Tween® 20 ([0029] of the published application (US PGPub No. 20240084025)); TOSOH® model TSK-GEL® G3000SW ([0047]), which are each a trade name or a mark used in commerce, has been noted in this application. The term(s) should be accompanied by the generic terminology; furthermore the term(s) should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term(s).
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks (see MPEP 608.01(v) and 608.01(u)).
Claim Objections
Claims 1-6 are objected to because of the following informalities:
Claim 1 recites “the amino acids of SEQ ID NO: 9”, in line 8, which should instead say “the amino acid sequence of SEQ ID NO: 9”, to better set forth the claimed subject matter.
Similarly, the phrase “the amino acids of SEQ ID NO...” is used in claim 1, 2, 3, 4, 5, and 6. It is recommended to amend each of these to “the amino acid sequence of SEQ ID NO...”.
Appropriate correction is required.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-12 are rejected under 35 U.S.C. 103 as being obvious over Tustian et al. (US20160024147) in view of Chung et al. (US20210024650, published 2/4/2021, filed 7/27/2020).
Tustian is drawn to a method for purifying a specific multimeric protein from a complex mixture of proteins via affinity chromatography, which comprises isolating a heterodimer (e.g. a bispecific antibody) from a complex mixture of monomers and homodimers via affinity chromatography (i.e. protein A chromatography) using a chaotropic agent ([0001], claim 1).
Tustian teaches that “Protein A chromatography” refers to a specific affinity chromatographic method that makes use of the affinity of the IgG binding domains of Protein A for the Fc portion of an immunoglobulin molecule ([0045]).
Tustian teaches that the bispecific antibodies and cell culture fluid used in these examples were expressed in CHO cells ([0014]; [0064]) and that the Protein A chromatography columns were loaded to 10-40 g binding antibody/L with “clarified cell culture fluid”, thus an antibody-containing filtrate as in the instant claim ([0066]). Methods for obtaining cell supernatants and filtering out unwanted cells and debris are well-known in the art (see also “Harvest” in Figure 4).
Tustian teaches loading a mixture of multimeric proteins onto an affinity matrix, and then eluting and collecting a heterodimeric protein from that matrix at a particular pH range and in a buffer containing a chaotropic agent ([0005]), and teaches that a buffered pH gradient is applied to the loaded affinity matrix where in one embodiment, the pH gradient is run from pH 6 to pH 3 ([0011]). Tustian species that the desired heterodimer product (e.g. the bispecific antibody) is eluted from the affinity matrix, is eluted from the affinity matrix with an elution range of about pH 5.5 to about pH 3.6 ([0011]). Tustian teaches that the elution buffer in one embodiment is 40 mM acetate and the chaotropic agent is CaCl2, at a range of 250-500 mM ([0011]).
Tustian also teaches in one example that harvested clarified cell culture fluid was loaded on a Protein A affinity matrix and was eventually eluted with a gradient of pH 5 to 3 in 40 mM acetate buffer ([0048]). Tustian teaches that the use of chaotropic salts such as calcium chloride as mobile phase modifiers in the elution buffer was shown to enhance the peak resolution and the subsequent purification of bsAb (see Table 2, last line, for CaCl2 the peak pH is 4.6 and yield and purity are both 100%). Elsewhere Tustian teaches that a similar buffer can contain 40 mM sodium acetate and 250 mM calcium chloride ([0068]).
Therefore, Tustian teaches a purification method comprises filtering a culture supernatant (e.g. obtaining a harvested clarified cell culture fluid, [0048]) of a bispecific antibody-producing cell line (e.g. claims 26-27) to obtain a crude antibody-containing filtrate; loading the filtrate onto a protein A affinity chromatography column ([0011], claim 4); and eluting the antibody from the column with a sodium acetate buffer containing CaCl2 (e.g. claims 17 and 22).
However, Tustian does not explicitly teach that the method is used to purify an anti-4-1BB/anti-HER2 bispecific antibody, as required in the instant claims.
Chung et al. (US20210024650) teaches an anti-4-1BB/anti-HER2 bispecific antibody (Title, Abstract, claim 1). The anti-HER2/anti-4-1 BB bispecific antibodies of Chung comprises IgG-scFv fusions wherein an scFv antibody fragment of one antigen is fused to c-terminal of IgG of another antigen, and teaches producing candidates in full-length IgG (anti-HER2 antibody)-scFv(anti-4-1 BB antibody) format or in full-length IgG (anti-4-1 BB antibody)-scFv(anti-HER2 antibody) ([0294]-[0295]). Chung teaches sequences of the heavy chains, light chains, scFvs and DNA segments used in preparing several exemplary bispecific antibodies are illustrated in Tables 21 to 29 ([0296]). Chung also teaches a production method which may comprise culturing a recombinant cell harboring the polynucleotide or the recombinant vector thereat, and optionally isolating and/or purifying the bispecific antibody from the culture medium (e.g. [0274]).
Regarding claims 1-3 and 6, the sequences disclosed in Chung et al. are essentially the same as those of the instant claims. Particularly, it is noted that the instant SEQ ID NO: 9 is identical to SEQ ID NO: 73 of Chung; instant SEQ ID NO: 11 is identical to SEQ ID NO: 75 of Chung; instant SEQ ID NO: 4 is identical to SEQ ID NO: 34 of Chung; instant SEQ ID NO: 8 is identical to SEQ ID NO: 25 of Chung; and instant SEQ ID NO: 10 is identical to SEQ ID NO: 83 of Chung. Further, the particular sequences of instant SEQ ID NOs: 1, 2, and 3; and instant SEQ ID NOs: 5, 6, and 7 are fully encompassed by instant SEQ ID NOs: 4 and 8, respectively.
Regarding claims 4 and 5, use of linker sequences are also taught in Chung et al. ([0240]-[0242]). The linker of the instant SEQ ID NO: 12, GSGSGSGSGSGSGSGSGS, is identical to SEQ ID NO: 86 of Chung. SEQ ID NO: 13, GGGGSGGGGSGGGGSGGGGS, is identical to SEQ ID NO: 87 of Chung.
Thus, to one of ordinary skill in the art, before the effective filing date of the instant invention, it would have been prima facie obvious to perform a bispecific antibody purification method, comprising the steps taught in Tustian including obtaining a harvested clarified cell culture fluid of a bispecific antibody-producing cell line (e.g. obtaining a crude antibody-containing filtrate); loading the antibody-containing mixture onto a protein A affinity chromatography column; and eluting the antibody from the column with a buffer containing sodium acetate and CaCl2 in order to purify and obtain a bispecific antibody comprising an IgG Fc region, including the anti-HER2/anti-4-1 BB bispecific antibodies taught in Chung.
One would have been motivated to purify the antibody taught in Chung with any suitable antibody purification method known in the art, and Tustian teaches the advantages of using calcium chloride in the elution buffer for the predictable benefit of enhancing the purity and recovery of the bispecific antibody. The selection of a bispecific IgG-scFv antibody which is used in the purification method does not practically change the method taught in Tustian. Likewise, the choice of a purification method from among those known in the art in order to obtain the antibody taught in Chung would have been a matter of judicious selection to one having ordinary skill in the art.
Regarding claims 7 and 9, Tustian teaches that the elution buffer in one embodiment comprises 40 mM acetate with CaCl2 at a range of 250-500 mM.
Regarding claims 8 and 11, the instantly claimed concentration range of 75 to 125 mM CaCl2 is not taught in the prior art, however, to one having ordinary skill in the art it would have been a matter of routine optimization to arrive at the instantly claimed concentrations.
MPEP § 2144.05 describes that the determination of suitable or effective concentration of a known composition (or when performing a known method) can be determined by one of ordinary skill in the art through the use of routine or manipulative experimentation to obtain optimal results, as these are variable parameters attainable within the art. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). In the instant case, the concentration of CaCl2 would have been a known result- effective variable, as its presence in the elution buffer is taught to be important in Tustian, and one would have been motivated to optimize the amount of the chaotropic salt provided.
Regarding claims 10 and 12, Tustian teaches providing elution buffers in gradients of a range of about pH 5.5 to about pH 3.6, which overlaps with the claimed range of pH 3.5 to 4.0. MPEP § 2144.05 states that, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
In this case, the claimed pH concentration overlaps with that of the reference and in regards to the narrower claimed range, the determination of a suitable or effective pH value of the claimed inventions can be determined by one of ordinary skill in the art through the use of routine or manipulative experimentation to obtain optimal results, as these are variable parameters attainable within the art, and pH is recognized by the teachings of Tustian to be a result-effective variable.
From the teachings of the cited references, it is apparent that there would have been a reasonable expectation of success in combining the teachings therein to arrive at the claimed invention because both references pertain to bispecific antibodies comprising IgG heavy and light chains, while Tustian teaches that Protein A chromatography relies upon the binding to the IgG Fc region. It would have been predictable that the methods of Tustian were applicable to the binding and purification of the medically useful bispecific antibodies taught in Chung.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date, as evidenced by the cited references, especially in the absence of evidence to the contrary.
It is noted that Chung et al. qualifies as intervening prior art under U.S.C. 102(a)(1), as the publication date (1/28/2021) is prior to the filing date of the PCT application (1/21/2022) and the reference has a different inventive entity. The publication date is later than the filing date of KR10-2021-0010077 (1/25/2021). However, Applicant cannot rely upon the certified copy of the foreign priority application to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55.
When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216.
Further, the applied reference Chung et al. has a common Applicant with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See MPEP § 717.02.
Claims 1-12 are rejected under 35 U.S.C. 103 as being obvious over Tustian et al. (US20160024147) in view of “Hinner” (US 20190010248 to Pieris Pharmaceuticals) and “Park” (WO2020111913 to ABL Bio Inc, published 6/4/2020).
Tustian is drawn to a method for purifying a specific multimeric protein from a complex mixture of proteins via affinity chromatography, which comprises isolating a heterodimer (e.g. a bispecific antibody) from a complex mixture of monomers and homodimers via affinity chromatography (i.e. protein A chromatography) using a chaotropic agent ([0001], claim 1).
Tustian teaches that “Protein A chromatography” refers to a specific affinity chromatographic method that makes use of the affinity of the IgG binding domains of Protein A for the Fc portion of an immunoglobulin molecule ([0045]).
Tustian teaches that the bispecific antibodies and cell culture fluid used in these examples were expressed in CHO cells ([0014]; [0064]) and that the Protein A chromatography columns were loaded to 10-40 g binding antibody/L with “clarified cell culture fluid”, thus an antibody-containing filtrate as in the instant claim ([0066]). Methods for obtaining cell supernatants and filtering out unwanted cells and debris are well-known in the art (see also “Harvest” in Figure 4).
Tustian teaches loading a mixture of multimeric proteins onto an affinity matrix, and then eluting and collecting a heterodimeric protein from that matrix at a particular pH range and in a buffer containing a chaotropic agent ([0005]), and teaches that a buffered pH gradient is applied to the loaded affinity matrix where in one embodiment, the pH gradient is run from pH 6 to pH 3 ([0011]). Tustian species that the desired heterodimer product (e.g. the bispecific antibody) is eluted from the affinity matrix, is eluted from the affinity matrix with an elution range of about pH 5.5 to about pH 3.6 ([0011]). Tustian teaches that the elution buffer in one embodiment is 40 mM acetate and the chaotropic agent is CaCl2, at a range of 250-500 mM ([0011]).
Tustian also teaches in one example that harvested clarified cell culture fluid was loaded on a Protein A-based resin and was eluted with a gradient of pH 5 to 3 in 40 mM acetate buffer ([0048]). Tustian teaches that the use of chaotropic salts such as calcium chloride as mobile phase modifiers in the elution buffer was shown to enhance the peak resolution and the subsequent purification of bsAb (see Table 2, last line, where for CaCl2 the peak pH is 4.6 and yield and purity are both 100%). Elsewhere Tustian teaches that a similar buffer can contain 40 mM sodium acetate and 250 mM calcium chloride ([0068]).
Therefore, Tustian teaches a purification method comprises filtering a culture supernatant (e.g. obtaining a harvested clarified cell culture fluid, [0048]) of a bispecific antibody-producing cell line (e.g. claims 26-27) to obtain a crude antibody-containing filtrate; loading the filtrate onto a protein A affinity chromatography column ([0011], claim 4); and eluting the antibody from the column with a sodium acetate buffer containing CaCl2 (e.g. claims 17 and 22).
However, Tustian does not explicitly teach that the method is used to purify an anti-4-1BB/anti-HER2 bispecific antibody, as required in the instant claims, nor the specific sequences claimed herein.
Hinner teaches fusion polypeptides specific for both CD137 and HER2/neu, which fusion polypeptide can be useful for directing CD137 clustering and activation to HER2/neu-positive tumor cells (Abstract, Claim 1, [0011]-[0012]). Hinner teaches that CD137 is a co-stimulatory immune receptor ([0004]), useful for anti-tumor therapies ([0006]-[0010]) and teaches that CD137 is also known as “4-1BB” or “tumor necrosis factor receptor superfamily member 9 (TNFRSF9)” or “induced by lymphocyte activation (ILA)” ([0014]). Thus, Hinner teaches bispecific antibodies for HER2 and 4-1BB, as so instantly claimed.
Hinner teaches that by causing the simultaneous binding to HER2 on tumor cells and CD137 on the surface of effector cells such as T-cells or NK cells, the fusion polypeptides of the disclosure may cause HER2-dependent effector-cell activation, whereby the effector cell of the immune system actively lyses the HER2-expressing tumor cell ([0074]).
Hinner teaches that the CD137/HER2 bispecific fusion protein has an Fc portion of immunoglobulin and that the Fc portion of the immunoglobulin included in a fusion polypeptide of the disclosure may contribute to maintaining the serum levels of the fusion polypeptide, critical for its stability and persistence in the body ([0076]).
Hinner teaches that the first binding domain comprises a full-length immunoglobulin or an antigen-binding domain thereof specific for HER2/neu, which may be an immunoglobulin that is a monoclonal antibody against HER2/neu. Hinner describes that a examples for such immunoglobulins include Trastuzumab ([0083]).
Hinner teaches that the immunoglobulin specific for HER2/neu as included in such fusion polypeptide, can comprise an antibody having the heavy and light chains provided by SEQ ID NOs: 3 and 4 ([0079]). It is noted that SEQ ID NO:3 of Hinner is 100% identical to SEQ ID NO: 9 of the instantly claimed heavy chain, and SEQ ID NO: 4 is 100% identical to the instantly recited SEQ ID NO: 11, for the light chain of the anti-HER2 antibody (see alignments below)
In regards to claims 4 and 5, Hinner teaches that a peptide linker may be used between the subunits of the fusion protein, and teaches a (Gly4Ser)3 linker (GGGGSGGGGSGGGGS) as shown in SEQ ID NO: 19 ([0066]).
Hinner teaches “[i]n some embodiments, the CD137-specific subunit included in a fusion polypeptide of the disclosure may be a full-length immunoglobulin or an antigen-binding domain thereof that is specific for CD137” ([0068]). Hinner teaches that monoclonal anti-CD137 specific antibodies are known in the art (“reference” SEQ ID NOs: 47, 48, 49, and 50; [0217]). However, Hinner does not disclose the sequences of the instantly claimed anti-4-1BB antibody.
Park discloses an anti-4-1BB antibody or an antigen-binding fragment thereof capable of enhancing immune response and/or treating tumor (cancer) in a mammal (Title, Abstract). Park teaches that the anti-4-1BB antibody or an antigen-binding fragment thereof is characterized by localizing and/or activating only in tumor microenvironment (TME) and/or considerably reducing liver toxicities compared to pre-existing anti-4-1BB antibodies (pg. 1, lines 21-27).
Park teaches anti-4-1BB antibodies (41B01.01, Table 3 and 41B01.03, Table 5) comprising a light chain variable region of an anti-4-1BB specific antibody comprising the instantly recited amino acid sequences of SEQ ID NOs: 1, 2, and 3, which are identical to SEQ ID NOs: 12, 14, and 16 of Park, respectively. Park also teaches a heavy chain variable region of anti-4-1 BB antibody comprising the instantly recited amino acid sequences of SEQ ID NOs: 5, 6, and 7, which are identical to SEQ ID NOs: 1, 4, and 8 of Park, respectively. See e.g. pg 3, lines 8-16 and claim 2, alternative (b): “(b) a CDR-H1 of SEQ ID NO: 1, a CDR-H2 of SEQ ID NO: 4, a CDR-H3 of SEQ ID NO: 8, a VL CDR1 of SEQ ID NO: 12, a VL CDR2 of SEQ ID NO: 14, and a VL CDR3 of SEQ ID NO: 16” .
Park also teaches preparing scFV antibodies against 4-1BB, including that of 41B01.03 (scFV), demonstrated in Table 12, having a light chain variable region (VL) of SEQ ID NO: 62, and a heavy chain variable region of SEQ ID NO: 58. (see pg. 39).
Regarding claims 2 and 3, the instantly claimed heavy chain comprising SEQ ID NO: 8 is 100% identical to SEQ ID NO: 58 of Park and the instantly claimed light chain comprising SEQ ID NO: 4 is 100% identical to SEQ ID NO: 62 of Park. Park teaches that the anti-4-1BB antibody or an antigen-binding fragment thereof may comprise a heavy chain variable region comprising or consisting essentially of SEQ ID NO: 18, 19, 20, 21, 22, 23, 39, 57, 58, 59, or 60; and a light chain variable region comprising or consisting essentially of an amino acid sequence of SEQ ID NO: 24, 25, 26, 61, or 62 (pg 3, lines 17-21 of the description in Park, and claim 3).
Regarding the identity of the linker sequence as in claims 4 and 5, Park teaches (pg 39, lines 7-10) using various types of peptide linkers known to the art, including “(GGGGS)4”, the same as instantly claimed SEQ ID NO:13, or “(GS)9” which is the same as instantly claimed SEQ ID NO: 12. The antibody scFV 41B01.03 of Park comprises SEQ ID NO:56 as the linker, which is identical to that of SEQ ID NO:13 of the instant claim (see e.g. Table 12).
To one of ordinary skill in the art, before the effective filing date of the instant invention, it would have been prima facie obvious to perform a bispecific antibody purification method, comprising the steps taught in Tustian including obtaining a harvested clarified cell culture fluid of a bispecific antibody-producing cell line (e.g. obtaining a crude antibody-containing filtrate); loading the antibody-containing mixture onto a protein A affinity chromatography column; and eluting the antibody from the column with a buffer containing sodium acetate and CaCl2 in order to purify and obtain a bispecific antibody comprising a fusion protein comprising a region specific for 4-1BB and an IgG antibody against HER2, comprising SEQ ID NO: 9 and 11, as taught in Hinner, wherein the 4-1BB/CD137-specific subunit comprises an scFV anti-4-1BB antibody taught in Park.
One would have been motivated to purify the antibody taught in Chung with any suitable antibody purification method known in the art, and Tustian teaches the advantages of using calcium chloride in the elution buffer for the predictable benefit of enhancing the purity and recovery of the bispecific antibody. The selection of any bispecific IgG-scFv antibody of similar fusion protein to be used with the purification method does not practically change the method taught in Tustian. Likewise, the choice of a purification method from among those known in the art in order to obtain the bispecific fusion proteins taught in Hinner would have been a matter of judicious selection to one having ordinary skill in the art.
MPEP § 2143.I., KSR Rationale D, describes that it is obvious to apply a known technique to a known device, method, or product ready for improvement to yield predictable results. In this case, the purification techniques used for bispecific antibodies taught in Tustian are applicable to purifying a bispecific fusion protein such as those taught in Hinner.
Regarding the selection of the particular anti-HER2 and anti-4-1BB subunits, an anti-4-1BB scFV antibody comprising the instantly recited sequences of SEQ ID NO: 4 and SEQ ID NO:8 is explicitly taught in Park, and one would have been motivated to substitute this particular anti-4-1BB antibody because Park teaches that the antibodies and therapeutics having such a sequence taught therein have considerably reducing liver toxicity compared to pre-existing anti-4-1BB antibodies (pg. 1, lines 21-27). One would have been motivated by the combined teachings of Hinner and Park to produce the anti-4-1BB/HER2 bispecific antibody according to the instant claims, because Hinner teaches that the co-targeting of an anti4-1BB (anti-CD137) antibody to tumors expressing HER2 further reduces the associated toxicity of previously known anti 4-1BB mABs, and the instantly claimed sequence is taught in Hinner, and this sequence is derived from a well-known HER2 targeting antibody in the art (e.g. trastuzumab). From the teachings of both references, would of ordinary skill would conclude that a HER2 sequence taught in Hinner combined with an improved anti-4-1BB scFV of Park would have predictably resulted in a dual-targeted cancer therapeutic with reduced toxicity and side-effects.
In regards to claims 4 and 5, the selection of any of these linker sequence from among those known to the art, including these two linkers (SEQ ID NOs: 13 and 12) taught explicitly in Park, would have been a matter of judicious selection to one of ordinary skill in the art.
Claim 6 recites that the heavy chain of the anti-4-1-BB/anti-HER2 bispecific antibody consists of the amino acids of SEQ ID NO: 10, which is a chimera of SEQ ID NOs: 9, 12, 4, 13, and 8 in that specific order (see Table 4 of the instant disclosure). One having ordinary skill in the art would have easily envisioned the fusion protein of SEQ ID NO: 10, as this would amount to the combination of known sequences with known linkers according to the teachings of the art. As one sought to combine the antibodies of Hinner and Park, they would have arrived at a chimeric sequence comprising SEQ ID NO:3 of Hinner (identical to instant SEQ ID NO: 9), with the scFV fragment taught in Park comprising SEQ ID NO: 62, SEQ ID NO:56, and SEQ ID NO: 58 (identical to instant SEQ ID NOs: 4, 13, and 8). The selection of any suitable linker, including that of SEQ ID NO:12, would have been a matter of judicious selection. Thus, the claimed sequence SEQ ID NO: 10 (comprising SEQ ID NOs: 9, 12, 4, 13, and 8) and subsequent purification thereof ,would have been predictable and obvious to one of ordinary skill.
Regarding the further limitations of claims 7 and 9, Tustian teaches that the elution buffer in one embodiment comprises 40 mM acetate with CaCl2 at a range of 250-500 mM.
Regarding claims 8 and 11, the instantly claimed concentration range of 75 to 125 mM CaCl2 is not taught in the prior art, however, to one having ordinary skill in the art it would have been a matter of routine optimization to arrive at the instantly claimed concentrations.
MPEP § 2144.05 describes that the determination of suitable or effective concentration of a known composition (or when performing a known method) can be determined by one of ordinary skill in the art through the use of routine or manipulative experimentation to obtain optimal results, as these are variable parameters attainable within the art. Where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation. In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). In the instant case, the concentration of CaCl2 would have been a known result- effective variable, as its presence in the elution buffer is taught to be important in Tustian, and one would have been motivated to optimize the amount of the chaotropic salt provided.
Regarding claims 10 and 12, Tustian teaches providing elution buffers in gradients of a range of about pH 5.5 to about pH 3.6, which overlaps with the claimed range of pH 3.5 to 4.0. MPEP § 2144.05 states that, in the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990). Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955)
In this case, the claimed pH concentration overlaps with that of the reference and in regards to the narrower claimed range, the determination of a suitable or effective pH value of the claimed inventions can be determined by one of ordinary skill in the art through the use of routine or manipulative experimentation to obtain optimal results, as these are variable parameters attainable within the art, and pH is recognized by the teachings of Tustian to be a result-effective variable.
It would have been predictable to one having ordinary skill in the art that the methods of Tustian were applicable to the purification of the therapeutic anti-cancer fusion proteins made obvious by the combination of Hinner and Park, and it would have been obvious to produce and purify a bispecific anti-4-1BB/anti-Her2 antibody having the instantly claimed sequences, all of which are known to the art.
From the teachings of the cited references, it is apparent that there would have been a reasonable expectation of success in combining the teachings therein to arrive at the claimed invention because the references pertain to bispecific proteins and/or antibodies comprising IgG heavy and light chains, both Hinner and Park pertain to binding agents for 4-1BB, and Tustian teaches that Protein A chromatography relies upon the binding to the IgG Fc region.
Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art prior to the effective filing date, as evidenced by the cited references, especially in the absence of evidence to the contrary.
Conclusion
No claims are allowed.
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/A.T.M./Examiner, Art Unit 1655
/ANAND U DESAI/Supervisory Patent Examiner, Art Unit 1655
Appendix A: Sequence alignments for Chung et al. (US 20210024650)
Sequence 73, US/16939536A and instant SEQ ID NO: 9
Publication No. US20210024650A1
GENERAL INFORMATION
APPLICANT: ABL Bio Inc.
APPLICANT: YUHAN CORPORATION
TITLE OF INVENTION: ANTI-HER2/ANTI-4-1BB BISPECIFIC ANTIBODY AND USE THEREOF
SEQ ID NO 73
LENGTH: 450
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic_heavy chain of anti-HER2 antibody
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
||||||||||||||||||||||||||||||
Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
Sequence 34, US/16939536A and Instant SEQ ID NO: 4
Publication No. US20210024650A1
GENERAL INFORMATION
APPLICANT: ABL Bio Inc.
APPLICANT: YUHAN CORPORATION
TITLE OF INVENTION: ANTI-HER2/ANTI-4-1BB BISPECIFIC ANTIBODY AND USE THEREOF
SEQ ID NO 34
LENGTH: 110
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic_light chain variable region of anti-4-1BB antibody
(mutated 1A10 M12, 1A10 M13, 1A12M1)
Query Match 100.0%; Score 582; Length 110;
Best Local Similarity 100.0%;
Matches 110; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QSVLTQPPSASGTPGQRVTISCSGSSSNIGNNYVTWYQQLPGTAPKLLIYADSHRPSGVP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QSVLTQPPSASGTPGQRVTISCSGSSSNIGNNYVTWYQQLPGTAPKLLIYADSHRPSGVP 60
Qy 61 DRFSGSKSGTSASLAISGLRSEDEADYYCATWDYSLSGYVFGCGTKLTVL 110
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DRFSGSKSGTSASLAISGLRSEDEADYYCATWDYSLSGYVFGCGTKLTVL 110
Sequence 25, US/16939536A and instant SEQ ID NO: 8
Publication No. US20210024650A1
GENERAL INFORMATION
APPLICANT: ABL Bio Inc.
APPLICANT: YUHAN CORPORATION
TITLE OF INVENTION: ANTI-HER2/ANTI-4-1BB BISPECIFIC ANTIBODY AND USE THEREOF
SEQ ID NO 25
LENGTH: 121
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic_heavy chain variable region of anti-4-1BB antibody
(mutated 1A10 M4, 1A10 M12)
Query Match 100.0%; Score 640; Length 121;
Best Local Similarity 100.0%;
Matches 121; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYDMSWVRQAPGKCLEWVSWISYSGGSIYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYDMSWVRQAPGKCLEWVSWISYSGGSIYY 60
Qy 61 ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDAQRNSMREFDYWGQGTLVTVS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDAQRNSMREFDYWGQGTLVTVS 120
Qy 121 S 121
|
Db 121 S 121
Sequence 75, US/16939536A and instant SEQ ID NO:11
Publication No. US20210024650A1
GENERAL INFORMATION
APPLICANT: ABL Bio Inc.
APPLICANT: YUHAN CORPORATION
TITLE OF INVENTION: ANTI-HER2/ANTI-4-1BB BISPECIFIC ANTIBODY AND USE THEREOF
SEQ ID NO 75
LENGTH: 214
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic_light chain of anti-HER2 antibody
Query Match 100.0%; Score 1110; Length 214;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
Qy 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPP 120
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
Sequence 83, US/16939536A vs Instant SEQ ID NO: 10
Publication No. US20210024650A1
GENERAL INFORMATION
APPLICANT: ABL Bio Inc.
APPLICANT: YUHAN CORPORATION
TITLE OF INVENTION: ANTI-HER2/ANTI-4-1BB BISPECIFIC ANTIBODY AND USE THEREOF
SEQ ID NO 83
LENGTH: 719
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic_heavy chain of bispecific antibody(HER2(WT)x1A10 M12)
Query Match 100.0%; Score 3836; Length 719;
Best Local Similarity 100.0%;
Matches 719; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSGSGSGSGSGSGSGSGSQSVLTQPPSASG 480
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGKGSGSGSGSGSGSGSGSGSQSVLTQPPSASG 480
Qy 481 TPGQRVTISCSGSSSNIGNNYVTWYQQLPGTAPKLLIYADSHRPSGVPDRFSGSKSGTSA 540
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 481 TPGQRVTISCSGSSSNIGNNYVTWYQQLPGTAPKLLIYADSHRPSGVPDRFSGSKSGTSA 540
Qy 541 SLAISGLRSEDEADYYCATWDYSLSGYVFGCGTKLTVLGGGGSGGGGSGGGGSGGGGSEV 600
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 541 SLAISGLRSEDEADYYCATWDYSLSGYVFGCGTKLTVLGGGGSGGGGSGGGGSGGGGSEV 600
Qy 601 QLLESGGGLVQPGGSLRLSCAASGFTFSSYDMSWVRQAPGKCLEWVSWISYSGGSIYYAD 660
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 601 QLLESGGGLVQPGGSLRLSCAASGFTFSSYDMSWVRQAPGKCLEWVSWISYSGGSIYYAD 660
Qy 661 SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDAQRNSMREFDYWGQGTLVTVSS 719
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 661 SVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDAQRNSMREFDYWGQGTLVTVSS 719
Appendix B: Sequence alignments for Hinner (US 20190010248)
US-18-273-888-9 and SEQ ID NO: 3 of Hinner (US20190010248)
RESULT 1
SEQIDNO-3
Query Match 100.0%; Score 2412; DB 1; Length 450;
Best Local Similarity 100.0%;
Matches 450; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGGSLRLSCAASGFNIKDTYIHWVRQAPGKGLEWVARIYPTNGYTRY 60
Qy 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISADTSKNTAYLQMNSLRAEDTAVYYCSRWGGDGFYAMDYWGQGTLVTVSS 120
Qy 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 ASTKGPSVFPLAPSSKSTSGGTAALGCLVKDYFPEPVTVSWNSGALTSGVHTFPAVLQSS 180
Qy 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GLYSLSSVVTVPSSSLGTQTYICNVNHKPSNTKVDKKVEPKSCDKTHTCPPCPAPELLGG 240
Qy 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 PSVFLFPPKPKDTLMISRTPEVTCVVVDVSHEDPEVKFNWYVDGVEVHNAKTKPREEQYN 300
Qy 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 STYRVVSVLTVLHQDWLNGKEYKCKVSNKALPAPIEKTISKAKGQPREPQVYTLPPSREE 360
Qy 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 MTKNQVSLTCLVKGFYPSDIAVEWESNGQPENNYKTTPPVLDSDGSFFLYSKLTVDKSRW 420
Qy 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
||||||||||||||||||||||||||||||
Db 421 QQGNVFSCSVMHEALHNHYTQKSLSLSPGK 450
US-18-273-888-11 and SEQ ID NO: 4 of Hinner (US20190010248)
RESULT 1
SEQIDNO-4
Query Match 100.0%; Score 1110; DB 1; Length 214;
Best Local Similarity 100.0%;
Matches 214; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQDVNTAVAWYQQKPGKAPKLLIYSASFLYSGVPS 60
Qy 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPP 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 RFSGSRSGTDFTLTISSLQPEDFATYYCQQHYTTPPTFGQGTKVEIKRTVAAPSVFIFPP 120
Qy 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 SDEQLKSGTASVVCLLNNFYPREAKVQWKVDNALQSGNSQESVTEQDSKDSTYSLSSTLT 180
Qy 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
||||||||||||||||||||||||||||||||||
Db 181 LSKADYEKHKVYACEVTHQGLSSPVTKSFNRGEC 214
Appendix C: Sequence alignments for Park (WO2020111913)
SEQ ID NO: 4 and SEQ ID NO: 62 of PCT/KR2019/016863/ US20220242961A1/ WO2020111913
Sequence 62, US/17296752A
Publication No. US20220242961A1
GENERAL INFORMATION
APPLICANT: ABL Bio Inc.
TITLE OF INVENTION: ANTI-4-1BB ANTIBODY AND USE THEREOF
SEQ ID NO 62
LENGTH: 110
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic_Light chain variable region of anti-4-1BB scFv
Query Match 100.0%; Score 582; Length 110;
Best Local Similarity 100.0%;
Matches 110; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QSVLTQPPSASGTPGQRVTISCSGSSSNIGNNYVTWYQQLPGTAPKLLIYADSHRPSGVP 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QSVLTQPPSASGTPGQRVTISCSGSSSNIGNNYVTWYQQLPGTAPKLLIYADSHRPSGVP 60
Qy 61 DRFSGSKSGTSASLAISGLRSEDEADYYCATWDYSLSGYVFGCGTKLTVL 110
||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 DRFSGSKSGTSASLAISGLRSEDEADYYCATWDYSLSGYVFGCGTKLTVL 110
SEQ ID NO: 8 and SEQ ID NO: 58 of PCT/KR2019/016863/ US20220242961A1/ WO2020111913
Sequence 58, US/17296752A
Publication No. US20220242961A1
GENERAL INFORMATION
APPLICANT: ABL Bio Inc.
TITLE OF INVENTION: ANTI-4-1BB ANTIBODY AND USE THEREOF
SEQ ID NO 58
LENGTH: 121
TYPE: PRT
ORGANISM: Artificial Sequence
FEATURE:
OTHER INFORMATION: Synthetic_Heavy chain variable region of anti-4-1BB scFv
Query Match 100.0%; Score 640; Length 121;
Best Local Similarity 100.0%;
Matches 121; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYDMSWVRQAPGKCLEWVSWISYSGGSIYY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLLESGGGLVQPGGSLRLSCAASGFTFSSYDMSWVRQAPGKCLEWVSWISYSGGSIYY 60
Qy 61 ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDAQRNSMREFDYWGQGTLVTVS 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ADSVKGRFTISRDNSKNTLYLQMNSLRAEDTAVYYCARDAQRNSMREFDYWGQGTLVTVS 120
Qy 121 S 121
|
Db 121 S 121
Instantly claimed fragments for the scFV of anti-4-1BB, see claim 1
SEQ ID NO: 1 - SGSSSNIGNNYVT
SEQ ID NO: 2 - ADSHRPS
SEQ ID NO: 3 - ATWDYSLSGYV
SEQ ID NO: 5 - SYDMS
SEQ ID NO: 6 - WISYSGGSIYYADSVKG
SEQ ID NO: 7 - DAQRNSMREFDY
WO 2020111913 (sequence information obtained from US 17/296,752)
SEQ ID NO: 12 - SGSSSNIGNNYVT
SEQ ID NO: 14 - ADSHRPS
SEQ ID NO: 16 - ATWDYSLSGYV
SEQ ID NO: 1 - SYDMS
SEQ ID NO: 4 - WISYSGGSIYYADSVKG
SEQ ID NO: 8 - DAQRNSMREFDY