DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Claims Status
Claims 1-23 are pending and presented for examination on the merits.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 10/11/2023, 06/17/2024, and 08/14/2026 has been considered by the Examiner. An initialed copy of the form PTO-1449 is attached to the office action.
Drawings
The drawings are objected to because of the following informalities:
Figures 1-5 are non-compliant with 37 CFR 1.84 (a)(1), which requires India ink, or its equivalent that “secures solid black lines” to be used for drawings. Because black/white ink is not used in Figures 1-5, some of the symbols in certain figures, such as the symbol for SD-233883-afuc in Figure 4E, cannot be distinguished.
Appropriate correction is required.
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The y-axis is unlabeled on the graph entitled “SD-837152-afuc (EGFR1)” of Figure 1C.
Appropriate correction is required.
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The size of the text in Figures 1A-1C is illegible and fails to comply with 37 CFR 1.84(l) and (p)(3), which requires reference characters, sheet numbers, and view numbers to be plain and legible. The scale to which a drawing is made must be large enough to show the mechanism without crowding when the drawing is reduced in size to two-thirds in reproduction. Indications such as "actual size" or "scale 1/2" on the drawings are not permitted since these lose their meaning with reproduction in a different format.
Appropriate correction is required.
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Abstract
The abstract of the disclosure is objected to because of the following informality:
The abstract of the disclosure fails to define “EGFRvIII” at its first usage in line 1. A corrected abstract of the disclosure is required and must be presented on a separate sheet, apart from any other text. See MPEP § 608.01(b).
Appropriate correction is required.
Specification
The disclosure is objected to because of the following informalities:
The specification recites “SEQ ID NOs: 7, 17, 27, 37, 47, 57, 67, 77, 87, 97, 107, 117, and 127” on pages 2 and 43 in paragraphs [0008] and [0106], respectively, and in Table 11 on pages 31-43. However, because the instant application was filed after July 1, 2022, the rules governing sequence disclosures are dictated by WIPO ST.26 which do not permit amino acid sequences of less than 4 amino acids being included in the Sequence Listing. Therefore, SEQ ID NOs: 7, 17, 27, 37, 47, 57, 67, 77, 87, 97, 107, 117, and 127 are technically “skipped sequences” and are not associated with the sequence “GAS” in the sequence listing. Deletion of “SEQ ID NOs: 7, 17, 27, 37, 47, 57, 67, 77, 87, 97, 107, 117, and 127” from the specification and replacement with “GAS” would be remedial (if it is not already present). Upon amendment, Applicant should point to the original sequence listing in the parent application as basis for inserting “GAS” in place of “SEQ ID NOs: 7, 17, 27, 37, 47, 57, 67, 77, 87, 97, 107, 117, and 127” if there is not currently literal support for the amendment.
Appropriate correction is required.
The specification contains trademarked terms:
“Tween-20” in paragraph [0073];
“Phage-CompetentTM” in paragraph [0066]; and
“LIVE/DEADTM” in paragraph [0087],
but does not provide the generic terminology:
The use of the terms “Tween-20” in paragraph [0073], “Phage-Competent” in paragraph [0066], and “LIVE-DEADTM” in paragraph [0087], which are trade names or a mark used in commerce, have been noted in this application. The terms should be accompanied by the generic terminology; furthermore, the terms should be capitalized wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Appropriate correction is required.
Claim Objections
Claim 1 is objected to because of the following informality:
Lines 1-11 recite: “an anti-Epidermal Growth Factor Receptor version III (EGFRvIII) antibody or antigen binding domain thereof, wherein the antibody or antigen binding domain comprises:
a heavy chain variable domain (VH) complementarity determining region (CDR) 1, VH CDR2 and VH CDR3 comprising an amino acid sequence of any one of the following SEQ ID NOS: 3, 4, 5; 13, 14, 15; 23, 24, 25; 33, 34, 35; 43, 44, 45; 53, 54, 55; 63, 64, 65; 73, 74, 75; 83, 84, 85; 93, 94, 95; 103, 104, 105; 113, 114, 115; or 123, 124, 125, respectfully; and
a light chain variable domain (VL) complementarity determining region (CDR) 1, VL CDR2, and VL CDR3 comprising an amino acid sequence of any one of the following SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; or 126, 127, 128, respectively,”
For clarity, Applicant should revise the claim language to recite: “an anti-Epidermal Growth Factor Receptor version III (EGFRvIII) antibody or antigen binding domain thereof, wherein the antibody or antigen binding domain comprises:
a heavy chain variable domain (VH) complementarity determining region (CDR) 1, VH CDR2 and VH CDR3 comprising an amino acid sequence of any of SEQ ID NOs: 3, 4, 5; SEQ ID NOs: 13, 14, 15; SEQ ID NOs: 23, 24, 25; SEQ ID NOs: 33, 34, 35; SEQ ID NOs: 43, 44, 45; SEQ ID NOs: 53, 54, 55; SEQ ID NOs: 63, 64, 65; SEQ ID NOs: 73, 74, 75; SEQ ID NOs: 83, 84, 85; SEQ ID NOs: 93, 94, 95; SEQ ID NOs: 103, 104, 105; SEQ ID NOs: 113, 114, 115; or SEQ ID NOs: 123, 124, 125, respectfully; and
a light chain variable domain (VL) complementarity determining region (CDR) 1, VL CDR2, and VL CDR3 comprising an amino acid sequence of any of SEQ ID NOs: 6, 7, 8; SEQ ID NOs: 16, 17, 18; SEQ ID NOs: 26, 27, 28; SEQ ID NOs: 36, 37, 38; SEQ ID NOs: 46, 47, 48; SEQ ID NOs: 56, 57, 58; SEQ ID NOs: 66, 67, 68; SEQ ID NOs: 76, 77, 78; SEQ ID NOs: 86, 87, 88; SEQ ID NOs: 96, 97, 98; SEQ ID NOs: 106, 107, 108; SEQ ID NOs: 116, 117, 118; or SEQ ID NOs: 126, 127, 128, respectively,” which would be remedial.
Appropriate correction is required.
Claims 1-3 and 15 are objected to because of the following informalities:
Claim 1, lines 4-5 and line 9 recite: “any one of the following SEQ ID NOS:...”
Claim 2, line 2 recites: “any one of the following SEQ ID NOS:...”
Claim 3, line 2 recites: “any one of the following SEQ ID NOS:...”
Claim 15, lines 5-6 and line 10 recite: “any one of the following SEQ ID NOS:…”
The recitation of “the following” is unnecessary because the sequences are not being provided in a list such that use of “the following” would be necessary. Applicant should revise the claim language to recite “any of SEQ ID NOs:…,” which would be remedial.
Appropriate correction is required.
Claims 2-14 are objected to because of the following informality:
Claims 2-14, line 1 recites: “antibody or binding domain of claim 1…”
Since these claims dependent are upon claim 1, they must recite the same terminology regarding the anti-EGFRvIII antibody or antigen binding domain from claim 1, which states: “antibody or antigen binding domain thereof.” Applicant should revise the claim language in claims 2-14 to recite: “antibody or antigen binding domain,” which would be remedial.
Appropriate correction is required.
Claim 9 is objected to because of the following informality:
The word “as” in place of the word “an” in line 2. Replacing the word “as” with “an” would be remedial.
Appropriate correction is required.
Claim 10 is objected to because of the following informality:
Lines 1-4 recite: “the antibody or binding domain of claim 1, wherein the antibody comprises a heavy chain variable domain and light chain variable domain: SEQ ID NO: 1 and 2, 11 and 12, 21 and 22, 31 and 32, 41 and 42, 51 and 52, 61 and 62, 71 and 72, 81 and 82, 91 and 92, 101 and 102, 111 and 112, or 121 and 122, respectively.”
For clarity, Applicant should revise the claim language to recite: “the antibody or antigen binding domain of claim 1, wherein the antibody or antigen binding domain comprises a heavy chain variable domain and a light chain variable domain comprising the amino acid sequences of: SEQ ID NOs: 1 and 2, SEQ ID NOs: 11 and 12, SEQ ID NOs: 21 and 22, SEQ ID NOs: 31 and 32, SEQ ID NOs: 41 and 42; SEQ ID NOs: 51 and 52; SEQ ID NOs: 61 and 62; SEQ ID NOs: 71 and 72, SEQ ID NOs: 81 and 82, SEQ ID NOs: 91 and 92, SEQ ID NOs: 101 and 102, SEQ ID NOs: 111 and 112, or SEQ ID NOs: 121 and 122, respectively,” which would be remedial.
Appropriate correction is required.
Claim 11 is objected to because of the following informality:
Lines 1-5 recite: “the antibody or binding domain of claim 1, wherein the antibody heavy chain is encoded by a nucleic acid and the antibody light chain is encoded by a nucleic acid with at least 80%, 85%, 90%, 95, 96, 97, 98, 99%, or 100% sequence identity to SEQ ID NOS: 9 and 10, 19 and 20, 29 and 30, 39 and 40, 49 and 50, 59 and 60, 69 and 70, 79 and 80, 89 and 90, 99 and 100, 109 and 110, 119 and 120, or 129 and 130, respectively.”
For clarity, Applicant should revise the claim language to recite: “the antibody or antigen binding domain of claim 1, the antibody or binding domain of claim 1, wherein the antibody heavy chain is encoded by a nucleic acid and the antibody light chain is encoded by a nucleic acid with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity to SEQ ID NOs: 9 and 10, SEQ ID NOs: 19 and 20, SEQ ID NOs: 29 and 30, SEQ ID NOs: 39 and 40, SEQ ID NOs: 49 and 50, SEQ ID NOs: 59 and 60, SEQ ID NOs: 69 and 70, SEQ ID NOs: 79 and 80, SEQ ID NOs: 89 and 90, SEQ ID NOs: 99 and 100, SEQ ID NOs: 109 and 110, SEQ ID NOs: 119 and 120, or SEQ ID NOs: 129 and 130, respectively,” which would be remedial.
Appropriate correction is required.
Claim 15 is objected to because of the following informality:
Lines 1-12 recite: “a method of treating a disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen binding domain thereof, wherein the antibody or antigen binding domain comprises:
a heavy chain variable domain (VH) complementarity determining region (CDR) 1, VH CDR2 and VH CDR3 comprising an amino acid sequence of any one of the following SEQ ID NOS: 3, 4, 5; 13, 14, 15; 23, 24, 25; 33, 34, 35; 43, 44, 45; 53, 54, 55; 63, 64, 65; 73, 74, 75; 83, 84, 85; 93, 94, 95; 103, 104, 105; 113, 114, 115; or 123, 124, 125, respectfully; and
a light chain variable domain (VL) complementarity determining region (CDR) 1, VL CDR2, and VL CDR3 comprising an amino acid sequence of any one of the following SEQ ID NOS: 6, 7, 8; 16, 17, 18; 26, 27, 28; 36, 37, 38; 46, 47, 48; 56, 57, 58; 66, 67, 68; 76, 77, 78; 86, 87, 88; 96, 97, 98; 106, 107, 108; 116, 117, 118; or 126, 127, 128, respectively.”
For clarity, Applicant should revise the claim language to recite: “a method of treating a disease in a subject in need thereof, comprising administering to the subject a therapeutically effective amount of the antibody or antigen binding domain thereof, wherein the antibody or antigen binding domain comprises:
a heavy chain variable domain (VH) complementarity determining region (CDR) 1, VH CDR2 and VH CDR3 comprising an amino acid sequence of any of SEQ ID NOs: 3, 4, 5; SEQ ID NOs: 13, 14, 15; SEQ ID NOs: 23, 24, 25; SEQ ID NOs: 33, 34, 35; SEQ ID NOs: 43, 44, 45; SEQ ID NOs: 53, 54, 55; SEQ ID NOs: 63, 64, 65; SEQ ID NOs: 73, 74, 75; SEQ ID NOs: 83, 84, 85; SEQ ID NOs: 93, 94, 95; SEQ ID NOs: 103, 104, 105; SEQ ID NOs: 113, 114, 115; or SEQ ID NOs: 123, 124, 125, respectfully; and
a light chain variable domain (VL) complementarity determining region (CDR) 1, VL CDR2, and VL CDR3 comprising an amino acid sequence of any of SEQ ID NOs: 6, 7, 8; SEQ ID NOs: 16, 17, 18; SEQ ID NOs: 26, 27, 28; SEQ ID NOs: 36, 37, 38; SEQ ID NOs: 46, 47, 48; SEQ ID NOs: 56, 57, 58; SEQ ID NOs: 66, 67, 68; SEQ ID NOs: 76, 77, 78; SEQ ID NOs: 86, 87, 88; SEQ ID NOs: 96, 97, 98; SEQ ID NOs: 106, 107, 108; SEQ ID NOs: 116, 117, 118; or SEQ ID NOs: 126, 127, 128, respectively,” which would be remedial.
Appropriate correction is required.
Claim 20 is objected to because of the following informality:
Lines 1-4 recite: “a polynucleotide that comprises a nucleic acid sequence with at least 80%, 85%, 90%, 95, 96, 97, 98, 99%, or 100% sequence identity with SEQ ID NOS: 9 and 10, 19 and 20, 29 and 30, 39 and 40, 49 and 50, 59 and 60, 69 and 70, 79 and 80, 89 and 90, 99 and 100, 109 and 110, 119 and 120, or 129 and 130, respectively.”
For clarity, Applicant should revise the claim language to recite: “a polynucleotide that comprises a nucleic acid sequence with at least 80%, 85%, 90%, 95%, 96%, 97%, 98%, 99%, or 100% sequence identity with SEQ ID NOS: 9 and 10, SEQ ID NOs: 19 and 20, SEQ ID NOs: 29 and 30, SEQ ID NOs: 39 and 40, SEQ ID NOs: 49 and 50, SEQ ID NOs: 59 and 60, SEQ ID NOs: 69 and 70, SEQ ID NOs: 79 and 80, SEQ ID NOs: 89 and 90, SEQ ID NOs: 99 and 100, SEQ ID NOs: 109 and 110, SEQ ID NOs: 119 and 120, or SEQ ID NOs: 129 and 130, respectively,” which would be remedial.
Appropriate correction is required.
Claim 23 is objected to because of the following informality:
Line 2 states “an antibody of claims antibody of claim 1,” which is unclear. Therefore, the claim language in claim 23 could be revised to recite: “the antibody of claim 1,” which would be remedial.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 1, 4-9, 12-19, and 23 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Regarding claims 1 and 15, lines 8-11 and lines 9-12, respectively, recite VL CDR2 variable light chain sequences as set forth in SEQ ID NOs: 7, 17, 27, 37, 47, 57, 67, 77, 87, 97, 107, 117, and 127, which are “skipped sequences.” Because the instant application was filed after July 1, 2022, the application falls under the ST26 version of the Sequence rules. 37 CFR 1.831(j) states that a “Sequence listing XML” must not include any sequences having fewer than 10 specifically defined nucleotides, or fewer than 4 specifically defined amino acids. Because these sequences have fewer than 4 specifically defined amino acids, they are “skipped” in the sequence listing and therefore, there is no information in the Sequence listing for SEQ ID NOs: 7, 17, 27, 37, 47, 57, 67, 77, 87, 97, 107, 117, and 127, and therefore, the claims are indefinite as the amino acid sequences intended by reference to these identifiers cannot be determined. Replacement of the sequence identifier with the actual amino acid sequence that the identifier was to represent would be remedial.
Regarding claims 4-9, 12-14, and 23, these claims are dependent upon claim 1 without resolving the issue(s) identified above and are therefore included in the rejection. Amendment to claim 1 as set forth above would be remedial.
Regarding claims 16-19, these claims are dependent upon claim 15 without resolving the issue identified above and are therefore included in the rejection. Amendment to claim 15 as set forth above would be remedial.
Claim Rejections - 35 USC § 112(a)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-9, 12-19, and 23 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
Claimed Invention
Claims 1 and 15 are drawn to an antibody or antigen-binding domain thereof that binds to and inhibits EGFRvIII comprising sequences for CDRH1-H3 and CDRL1-L3, wherein:
CDRH1 comprises the amino acid sequence of SEQ ID NO: 3, 13, 23, 33, 43, 53, 63, 73, 83, 93, 103, 113, or 123;
CDRH2 comprises the amino acid sequence of SEQ ID NO: 4, 14, 24, 34, 44, 54, 64, 74, 84, 94, 104, 114, or 124;
CDRH3 comprises the amino acid sequence of SEQ ID NO: 5, 15, 25, 35, 45, 55, 65, 65, 75, 85, 95, 105, 115, or 125;
CDRL1 comprises the amino acid sequence of SEQ ID NO: 6, 16, 26, 36, 46, 56, 66, 76, 86, 96, 106, 116, or 126;
CDRL2 comprises the amino acid sequence of SEQ ID NO: 7 (GAS), 17 (GAS), 27 (GAS), 37 (GAS), 47 (GAS), 57 (GAS), 67 (GAS), 77 (GAS), 87 (GAS), 97 (GAS), 107 (GAS), 117 (GAS), or 127 (GAS);
CDRL3 comprises the amino acid sequence of SEQ ID NO: 8, 18, 28, 38, 48, 58, 68, 78, 88, 98, 108, 118, or 128.
However, the claim limitations as written fail to provide an adequate written description for such antibodies and antigen binding domains thereof that specifically bind and inhibit EGFRvIII because while the claims recite CDR structures for the VH and VL regions of the antibody, the claims encompass mixing and matching of VH/VL CDR1-3 to arrive at a functional antibody that specifically binds and inhibits EGFRvIII.
Claims 2-9, 12-14, 16-19, and 23 are dependent on the anti-EGFRvIII antibody or antigen binding domain thereof disclosed in claims 1 and/or 15 and have the same written description issue.
Scope of Disclosed Species
An antibody or antigen binding domain with a full set of VH CDRs (i.e., HCDR1-3) and the complementary VL CDRs (i.e., LCDR1-3) has written description. The instant specification teaches sets of complementary VH and VL amino acid sequences (which comprise of complementary VH CDR1-3 and VL CDR1-3 amino acid sequences) that have written description, wherein the VH and VL comprise the amino acid sequences of SEQ ID NOs: 1 and 2, SEQ ID NOs: 11 and 12, SEQ ID NOs: 21 and 22, SEQ ID NOs: 31 and 32, SEQ ID NOs: 41 and 42, SEQ ID NOs: 51 and 52, SEQ ID NOs: 61 and 62, SEQ ID NOs: 71 and 72, SEQ ID NOs: 81 and 82, SEQ ID NOs: 91 and 92, SEQ ID NOs: 101 and 102, SEQ ID NOs: 111 AND 112, or SEQ ID NOs: 121 and 122 (e.g., page 2, paragraph [0008], lines 11-14; pages 30-42, Table 11; page 44, paragraph [0109], lines 1-4), respectively.
However, the instant specification also teaches antibodies which mix and match CDRs of the heavy and light chain variable domains which also have the ability to bind their respective targets, but these antibodies do not have written description (e.g., page 2, paragraph [0008], lines 1-11; pages 30-43, Table 11; page 43, paragraph [0105], lines 1-8).
State of the Prior Art
At the time of the filing of the instant application, it is well established in the art, specifically in Almagro & Fransson (Frontiers in Bioscience, 01 January 2008, 13:1619-33; hereinafter “Almagro”), that the formation of an intact antigen-binding site in an antibody usually requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three complementarity determining regions (CDRs) which provide the majority of the contact residues for the binding of the antibody to its target epitope (e.g., Section 3, “Antibody Structure and the Antigen Binding Site”; Figure 1). While affinity maturation techniques can result in differences in the CDRs of the antibody compared to its parental antibody (e.g., page 3, “The IgG Molecule,” paragraphs 2-3), those techniques involve trial-and-error testing and the changes that maintain or improve affinity are not predictable a priori. Chiu et al. (Antibodies, 16 October 2019, 8(55):1-80; hereinafter “Chiu”) teaches the antigen binding of antibodies often results in conformational changes in the contact surface areas of both the antibody and the antigen (e.g., page 5, paragraph 1). Thus, it might be difficult to predict binding of a CDR to an epitope or difficult to determine what amino acids would be required in a CDR to bind to an epitope. Chiu further teaches that antibody modeling has been shown to be accurate for the framework region sequences, but CDR modeling requires further development and improvements (e.g., page 6, paragraph 2). Prediction of the structure of HCDR3 could not be accurately produced when given the Fv structures without their CDR-H3s (e.g., page 6, paragraph 2). Chiu teaches the quality of antibody structure prediction, particularly regarding CDR-H3, remains inadequate, and the results of antibody-antigen docking are also disappointing (e.g., page 11, paragraph 2).
In addition to changes within the CDR altering target binding, alterations to the CDR have been shown to dramatically alter antibody secretion. Hasegawa et al. (MAbs, July 2017, 9(5):854-873; hereinafter “Hasegawa”) teaches a pair of human IgG clones with a single amino acid substitution in the variable region was sufficient to alter the efficiency of immunoglobulin biosynthesis (e.g., page 866, last sentence, left column). Hasegawa teaches the 2 monoclonal antibodies (mAbs) differed only by one amino acid in the light chain’s CDR1 and that despite the near-identity of their primary sequences, the parental mAb secretes copious amounts of IgG to the culture media, while the variant mAb induces RB phenotypes extensively and secretes 20-fold less IgG (e.g., page 866, right column, paragraph 1). Importantly, the two model IgGs are by no means abnormal or defective as mAbs but demonstrate a profound impact of a single amino acid substitution on immunoglobulin biosynthesis (e.g., page 866, right column, paragraph 1).
Based on the state of the art, mixing and matching HCDR1-3 and LCDR1-3 amino acid sequences does not guarantee an antibody will bind a specific antigen. Altering one amino acid within the CDR sequences of the VH and VL regions can change how tightly an antibody binds its target or prevent antigen binding. Therefore, mixing and matching CDR sequences will not form a proper antigen binding domain that will bind to EGFRvIII as required by the instant claims.
Conclusion
As indicated by the art, mixing and matching VH CDR1-3 and VL CDR1-3 amino acid sequences does not guarantee an antibody will bind a specific antigen (i.e., EGFRvIII). Antibody-antigen binding requires highly precise molecular fitting. Therefore, one of ordinary skill in the art cannot envision randomly combining VH CDR1-3 and VL CDR1-3 amino acid sequences to result in a functional antibody that binds to and inhibits EGFRvIII.
Applicant can overcome the rejection of claims 1 and 15 by stating a specific SEQ ID NO for each of the amino acid sequences comprising CDR1-3 in the VH region of the anti-EGFRvIII antibody, in addition to stating a specific SEQ ID NO for each of the amino acid sequences comprising CDR1-3 in the VL region of the anti-EGFRvIII antibody. Claims 2-9, 12-14, 16-19, and 23 are dependent on claims 1 and/or 15 and have the same written description issue. Amendment to claims 1 and 15 as set forth above would be remedial.
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.
Claim(s) 20-22 are rejected under 35 U.S.C. 103 as being unpatentable over U.S. Patent No. 8,993,295 (hereinafter “Seed”) in view of Mauro & Chappell (hereinafter “Mauro”) and Carton et al (hereinafter “Carton”).
Seed teaches a polynucleotide sequence that has 58.3% sequence identity with the polynucleotide sequences set forth in SEQ ID NOs: 9 and 10 (instant claim 20) (e.g., page 119, Table 3; page 196, Sequence Listing). Seed also teaches that vectors are used to insert polynucleotide sequences (i.e., the target gene(s)) into host cells, wherein the host cells use their native transcription and translation machinery to express recombinant proteins (instant claims 21-22) (e.g., page 63, column 2, paragraph 3; page 64, column 1, paragraph 3).
Seed does not teach a polynucleotide sequence that has at least 80% sequence identity the polynucleotides sequences set forth in SEQ ID NOs: 9 and 10, but this is obvious in view of Mauro and Carton.
Regarding instant claim 20, Mauro teaches the process of codon optimization, which involves modifying the nucleotide sequence (i.e., nucleotide triplets/codons) of a gene to replace rare/less-favored codons with more frequently used/favored codons of the host organism, thereby increasing the efficiency of translation, resulting in higher levels of protein expression (e.g., page 1, Abstract of Mauro). Carton teaches a study demonstrating how codon optimization improves gene expression and the translational efficiency of a gene, wherein the translation rate in E. coli (i.e., host organism) was slowed when the target protein codon usage differed significantly from the average codon usage of the host organism, but was increased when the target protein codon usage was more similar to the average codon usage of the host organism (e.g., page 280, column 1, paragraph 2 of Carton). Carton also teaches that when codons rarely used in highly expressed E. coli proteins (i.e., Arginine-AGG/A and CGG, Glycine-GGA, Isoleucine-AUA, Proline-CCC, Leucine-CUA) are replaced with synonymous codons used at a higher frequency in recombinant protein coding sequences, target protein expression is increased (e.g., page 280, column 1, paragraph 2 of Carton).
It would have been prima facie obvious to a PHOSITA before the effective filing date of the claimed invention to utilize the process of codon optimization as taught in Mauro and Carton to modify the polynucleotide sequence having 58.3% sequence identity with the polynucleotide sequences set forth in SEQ ID NOs: 9 and 10 using synonymous mutations to match a host organism’s preferred codon bias, as taught in Seed, to form a polynucleotide with at least 80% sequence identity with the polynucleotide sequences set forth in SEQ ID NOs: 9 and 10, wherein the optimized polynucleotide sequence is inserted into a host cell via an expression vector. A PHOSITA would have been motivated to combine the process of codon optimization, as taught by Mauro and Carton, with the polynucleotide sequence having 58.3% sequence identity with the polynucleotide sequences set forth in SEQ ID NOs: 9 and 10, wherein the polynucleotide sequence is inserted into a host cell via an expression vector, as further taught by Seed, because: 1) DNA constructs intended for expression in a host organism/host cell may be modified to accommodate preferable codons for the host (e.g., page 63, column 1, paragraph 4 of Seed), 2) codon engineering according to a host cell’s codon bias increases the speed and efficiency of transcription and translation of a recombinant protein (e.g., page 285, column 1, paragraph 1 of Carton), and 3) synonymous codons are interchangeable without affecting protein structure and function, and replacing rare codons with frequently used codons increases protein production (page 3, “Critical analysis of codon-optimization,” paragraph 1 of Mauro). Therefore, a PHOSITA would have a reasonable expectation of success in using the process of codon optimization to form a polynucleotide that comprises a nucleic acid sequence with at least 80% sequence identity with SEQ ID NOs: 9 and 10, wherein the optimized polynucleotide sequence is inserted into a host cell via an expression vector.
Thus, the claims of Seed would have been prima facie obvious over Mauro and Carton, especially in absence of evidence to the contrary.
Conclusion
No claims are currently allowed.
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/MALIA NICOLE GREEN/Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643
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