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 .
Applicant previously canceled claims 1-59. Claims 60-79 are newly added. Claims 60-79 are currently pending and under examination.
Information Disclosure Statement
The Information Disclosure Statement filed February 09, 2023 has been considered.
Specification
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code (see Page 27, [0068]). Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
The use of the terms Phusion®, (Page 69, [00129], Page 73, [00134], Page 74, [00135]-[00136], Page 75, [00139], Page 76, [00140]-[00141], Page 77, [00144]), which is a trade name or a mark used in commerce, has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Claim Objections
Claims 62, 68, 71 and 77 are objected to because of the following informalities:
In claim 62, lines 5-6, “is ligated to the upstream of”, should read “is ligated upstream of”.
In claim 68, line 10, “the ligation product”, should read “the first ligation product”.
In claim 71, lines 4-5, “is ligated to the downstream of”, should read “is ligated downstream of”.
In claim 77, line 5, the sequence listed is missing a SEQ ID NO:. The sequence is interpreted as being SEQ ID NO: 57.
In claim 77, line 8, the sequence listed is missing a SEQ ID NO:. The sequence is interpreted as being SEQ ID NO: 58.
In claim 77, line 14, the sequence listed is missing a SEQ ID NO:. The sequence is interpreted as being SEQ ID NO: 82.
In claim 77, line 17, the sequence listed is missing a SEQ ID NO:. The sequence is interpreted as being SEQ ID NO: 84.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 60-77 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.
Claim 60 is considered vague and indefinite for the following reasons:
Claim 60 recites the limitation "the amplified population of nucleic acids" in lines 5-6. There is insufficient antecedent basis for this limitation in the claim.
Claim 60 recites the limitation "the chicken antibody" in lines 8-9 and 14-15. There is insufficient antecedent basis for this limitation in the claim.
Claims 61-77 depend from claim 60 and are therefore included in this rejection.
Claim 61 is considered vague and indefinite for the following reasons:
Claim 61 recites the limitation "the amplified population of nucleic acids" in lines 1-2. There is insufficient antecedent basis for this limitation in the claim.
Claim 61 recites the limitation "the sequence encoding the CDR" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claims 62, 67-72 depend from claim 61 and are therefore included in this rejection.
Claim 62 is considered vague and indefinite for the following reasons:
In claim 62, the terms “the overhang” in line 5 is unclear. Is this referring to the 3’ overhang, 5’ overhang, either or both?
Claim 62, recites the limitation "the first digestion product" in line 6. There is insufficient antecedent basis for this limitation in the claim.
Claims 68-72 depend from claim 62 and are therefore included in this rejection.
Claim 63 is considered vague and indefinite for the following reasons:
Claim 63 recites the limitation "the CDR boundary" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 63 recites the limitation "the boundary" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 63 recites the limitation "the sequencing encoding" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claims 64 depends from claim 63 and is therefore included in this rejection.
Claim 64 is considered vague and indefinite for the following reasons:
Claim 64 recites the limitation "the CDR boundary" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 66 is considered vague and indefinite for the following reasons:
Claim 66 recites the limitation "the length" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 66 recites the limitation "the mRNA" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 66 recites the limitation "the chicken antibody" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claim 67 is considered vague and indefinite for the following reasons:
Claim 67 recites the limitation "the CDR boundary" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 69 is considered vague and indefinite for the following reasons:
Claim 69 recites the limitation "the length" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 69 recites the limitation "the mRNA" in line 2. There is insufficient antecedent basis for this limitation in the claim.
Claim 69 recites the limitation "the chicken antibody" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim.
Claim 70 is considered vague and indefinite for the following reasons:
Claim 70 recites the limitation "the sequencing encoding" in line 3. There is insufficient antecedent basis for this limitation in the claim.
Claims 71-72 depend from claim 70 and are therefore included in this rejection.
Claim 71 is considered vague and indefinite for the following reasons:
Claim 71 recites the limitation "the second ligation product" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim.
Claim 76 is considered vague and indefinite for the following reasons:
In claim 76, line 1, the sequence “ACNNNNGTAYC” is unclear and confusing as well as missing a sequence identifier; sequence identifiers are required for a sequence with 10 or more enumerated and defined nucleotides. The Y is undefined and is therefore unclear; is this any nucleic acid as well?
In claim 76, line 2, the sequence “CGANNNNNNTGC” is missing a sequence identifier; sequence identifiers are required for a sequence with 10 or more enumerated and defined nucleotides.
In claim 76, line 3, the sequence “ACNNNNNCTCC” is missing a sequence identifier; sequence identifiers are required for a sequence with 10 or more enumerated and defined nucleotides.
In claim 76, line 5, the sequence “CAANNNNNGTGG” is missing a sequence identifier; sequence identifiers are required for a sequence with 10 or more enumerated and defined nucleotides.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 60-76 and 79 are rejected under 35 U.S.C. 102 (a)(1) and (a)(2) as being anticipated by Fischer et al. (U.S. Patent Application Publication US 2015/0119294 A1, published April 30, 2015).
Regarding claim 60, Fischer teaches a method of producing a population of nucleic acid molecules encoding a chicken complementary determining region (CDR) flanked by two human framework regions (FRs) (Page 2, [0012], Pages 4-5, [0025]-[0026], Page 17, [0184] and Fig. 2). Fischer teaches amplifying a first population of nucleic acid molecules encoding chicken antibodies with a first primer and a second primer under conditions sufficient to produce the amplified population of nucleic acid molecules encoding the chicken complementary determining region (CDR) (Pages 4-5, [0025]-[0026], Page 17, [0184] and Fig. 3). Fischer teaches the first primer anneals to a region upstream or downstream of a CDR of the chicken antibody (Page 17, [0184] and Fig. 3). Fischer teaches the first primer contains a restriction enzyme recognition site recognized by a restriction enzyme that cleaves at a location that is immediately upstream or downstream of the CDR and at a distance away from the recognition site and the second primer anneals to a region at a distance downstream of the CDR of the chicken antibody, if the first primer anneal upstream of the CDR or the second primer anneals to a region at a distance upstream of the CDR of the chicken antibody, if the first primer anneals downstream of the CDR (Page 4, [0021] and [0023], Page 17, [0184], Page 32, [0278] and Fig. 3).
Regarding claim 61, Fischer teaches digesting the amplified population of nucleic acid molecules with said restriction enzyme to produce a 5' overhang immediately upstream of the sequence encoding the CDR to produce a digestion product (Page 18, [0189], Page 28, [0268] and Figs. 2-3).
Regarding claim 62, Fischer teaches preparing a first ligation product by ligating said digestion product to a nucleic acid sequence encoding a first FR of a human antibody, wherein said first FR of a human antibody comprises an overhang region at its 3'-end compatible with the overhang region of said digestion product so that the first FR is ligated to the upstream of the first digestion product (Page 3, [0017]-[0019], Page 8, [0066], Page 18, [0189]-[0190], Page 28, [0268] and Figs. 2-3).
Regarding claims 63 and 64, Fischer teaches primers are designed to contain cleavage sites for type II restriction enzymes at the boundary of the site at which diversity is desired for example the CDR (Page 4, [0021]). Fischer teaches the Types II restriction enzyme cleaves at a defined distance from the CDR and the defined distance may be up to 20 bases, which includes cleaving at a location from 1-5 nucleotides of the CDR boundary and the CDR boundary is either internal or external of the sequencing encoding the CDR (Page 17-18, [0186] and [0188] and Figs. 1-4).
Regarding claim 65, Fischer teaches the restriction enzyme cleaves at a location that is at least 10 nucleotides away from the recognition site (Page 4, [0021], Pages 17-18, [0186] and [0188] and Figs. 1-4).
Regarding claim 66, Fischer teaches the second primer anneals to a region at a distance no greater than the length of the mRNA transcript downstream or upstream of the CDR of the chicken antibody (Page 4, [0021], Page 17, [0184], Page 32, [0277]-[0278] and Fig. 3).
Regarding claim 67, Fischer teaches 67. (New) The method of claim 61, wherein the 5' overhang that is immediately downstream is 1, 2, 3, 4, or 5 nucleotides of the CDR boundary. (Page 3, [0017]-[0019], Page 8, [0066], Page 18, [0189]-[0190], Page 28, [0268], Page 32, [0278] and Figs. 2-3).
Regarding claim 68, Fischer teaches preparing a second population of amplified nucleic acid molecules with a third primer and a fourth primer under conditions sufficient to produce the second amplified population of nucleic acid molecules encoding the chicken CDR (Page 4, [0021]-[0023], Page 14, [0135]-[0136], Page 15, [0145]-[0146], Page 17, [0184], Page 27, [0265], Page 28, [0268], Page 32, [0277]-[0280] and Example 1). Fischer teaches the third primer anneals to a region immediately downstream of the nucleic acid sequence encoding the CDR present in the first ligation product, wherein the third primer contains a restriction enzyme recognition site recognized by a restriction enzyme that cleaves at a location that is immediately downstream of the CDR and at a distance away from the recognition site (Page 4, [0021]-[0023], Page 14, [0135]-[0136], Page 15, [0145]-[0146], Page 17, [0184], Page 27, [0265], Page 28, [0268], Page 32, [0277]-[0280], Example 1 and Figs. 2-4). Fischer teaches the fourth primer anneals to a portion of the nucleic acid molecule encoding the first FR present in the first ligation product at a distance upstream of the CDR in the ligation product (Page 4, [0021]-[0023], Page 14, [0135]-[0136], Page 15, [0145]-[0146], Page 17, [0184], Page 27, [0265], Page 28, [0268], Page 32, [0277]-[0280], Example 1 and Figs. 2-4).
Regarding claim 69, Fischer teaches the second primer anneals to a region at a distance no greater than the length of the mRNA transcript downstream of the CDR of the chicken antibody (Page 4, [0021], Page 17, [0184], Page 32, [0277]-[0278] and Fig. 3).
Regarding claim 70, Fischer teaches digesting the second amplified population of nucleic acid molecules with said restriction enzyme to produce a 5' overhang immediately downstream of the sequence encoding the CDR to produce a second digestion product (Page 3, [0017]-[0019], Page 8, [0066], Page 18, [0189]-[0190], Page 28, [0268] and Figs. 2-3).
Regarding claim 71, Fischer teaches ligating the second digestion product to a nucleic acid sequence encoding a second FR of a human antibody to produce the second ligation product, wherein said second FR comprises an overhang region at its 5'-end compatible with the overhang region of said second digestion product, so that the second FR is ligated to the downstream of the second digestion product (Page 3, [0017]-[0019], Page 8, [0066], Page 18, [0189]-[0190], Page 20, [0211], Page 28, [0268] and Figs. 2-3).
Regarding claim 72, Fischer teaches comprising amplifying the second ligation product with a first FW primer that anneals to the first FR of the human antibody and a second primer that anneals to the second FR of the human antibody under conditions sufficient to produce the population of nucleic acid molecules encoding the CDR flanked by two FRs of a human antibody (Page 4, [0021]-[0023], Page 14, [0135]-[0136], Page 15, [0145]-[0146], Page 17, [0184], Page 27, [0265], Page 28, [0268], Page 32, [0277]-[0280], Page 2, [0012], Pages 4-5, [0025]-[0026], Page 17, [0184], Fig. 2 and Example 1).
Regarding claim 73, Fischer teaches the CDR is a chicken CDR1, CDR2, or CDR3 and the FRs are human FR1, FR2, FR3, or FR4 (Page 17, [0184], Page 5, [0025] and Page 3, [0017]).
Regarding claim 74, Fischer teaches the restriction enzyme is a Type IIS enzyme (Page 5, [0025]).
Regarding claim 75, Fischer teaches a first primer and third primer (Page 4, [0021]-[0023] and Example 1). Fischer teaches the primers may comprise a nucleic acid sequence comprising the formula: 5' -(N)xR(N)n-3', R is the recognition sequence, N is any nucleic acid base, such as naturally occurring, non-naturally occurring, or degenerate nucleic acid base, x is 0-11, and n is 1-21 (SEQ ID NOs: 212 and 213 and Page 4, [0021]-[0023]).
Regarding claim 76, Fischer teaches R is CGATC (SEQ ID NOs: 212 and 213 and Page 4, [0021]-[0023]).
Regarding claim 79, Fischer teaches an oligonucleotide that anneals to a region immediately upstream or downstream of CDR of a chicken antibody (Page 17, [0184] and Fig. 3). Fischer teaches said oligonucleotide comprises a restriction enzyme recognition site recognized by a restriction enzyme that cleaves at a distance downstream of the recognition site (Page 4, [0021] and [0023], Page 17, [0184], Page 32, [0278] and Fig. 3). Fischer teaches the oligonucleotide comprises the sequence of nucleic acid sequence comprising the formula: 5' -(N)xR(N)n-3', where R is the recognition sequence, N is any nucleic acid base, such as naturally occurring, non-naturally occurring, or degenerate nucleic acid base, x is 0-11 and n is 1-21 (SEQ ID NOs: 212 and 213 and Page 4, [0021]-[0023]).
Fischer teaches each and every limitation of claims 60-76 and 79, therefore Fischer anticipates claims 60-76 and 79.
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.
Claim 77 is rejected under 35 U.S.C. 103 as being unpatentable over Fischer et al. (U.S. Patent Application Publication US 2015/0119294 A1, published April 30, 2015, as applied to claims 60-76 and 79 above, in view of Park et al. (United States Patent US 9,193,994 B2, patented November 24, 2015, effectively filed April 19, 2013).
Regarding claim 77, Fischer teaches the first primer and third primer as discussed above.
Fischer does not teach or suggest that the first and third primer comprise a nucleic acid sequence comprises a sequence of 5'- GTGCAGNNNNNNNNNNNNNNN-3' (SEQ ID NO: 62), wherein N is any nucleic acid base, such as naturally occurring, non-naturally occurring, or degenerate nucleic acid base.
Park teaches polynucleotides including primers pairs to efficiently amplify target nucleic acids (Column 1, Lines 45-49 and Column 5, Line 30-Column 6, Line 2). Park teaches primers comprising the sequence 5'- GTGCAGNNNNNNNNNNNNNNN-3' (SEQ ID NO: 62) (Table 4, SEQ ID No: 85).
As a common field of endeavor both Fischer and Park disclose using primer pairs for amplification. It would have been prima facie obvious to one having ordinary skill in the art at the time of the invention to modify the method of Fischer by substituting the primers as taught by Park because it has been held that the simple substitution of one known element for another to obtain predictable results is obvious. In re Fout, 213 USPQ 532 (CCPA 1982), In re O'Farrell, 7 USPQ2d 1673 (Fed. Cir. 1988). Simply substituting the primers of Fischer with primers of Park with the sequence comprising a sequence of 5'- GTGCAGNNNNNNNNNNNNNNN-3' (SEQ ID NO: 62), would obtain expected predictable results because both Fischer and Park disclose methods for amplification using primer pairs.
Claim 78 is rejected under 35 U.S.C. 103 as being unpatentable over Fischer et al. (U.S. Patent Application Publication US 2015/0119294 A1, published April 30, 2015, as applied to claims 60-76 and 79 above, in view of Wu et al. (U.S. Patent Application Publication US 2010/0216975 A1, published August 26, 2010), cited on the IDS filed February 09, 2023.
Regarding claim 78, Fischer teaches a method of producing a library of nucleic acid molecules encoding humanized variable regions of antibodies (Page 2, [0012], Pages 4-5, [0025]-[0026], Page 17, [0184] and Fig. 2). Fischer teaches a first library of nucleic acid molecules encoding a chicken complementary determining region 1 (CDR1) domain, flanked by nucleic acid sequences encoding a human framework region 1 (FR1) and a human framework region 2 (FR2) (Page 2, [0012], Pages 4-5, [0025]-[0026], Page 17, [0184] and Fig. 2). Fischer teaches a second library of nucleic acid sequences encoding a chicken complementary determining region 2 (CDR2) domain, flanked by nucleic acid sequences encoding a human framework region 2 (FR2) and a human framework region 3 (FR3) (Page 2, [0012], Pages 4-5, [0024]-[0026], Page 17, [0184] and Fig. 2). Fischer teaches a third library of nucleic acid sequences encoding a chicken complementary determining region 3 (CDR3) domain, flanked by nucleic acid sequences encoding a human framework region 3 (FR3) and a human framework region 4 (FR4) (Page 2, [0012], Pages 4-5, [0024]-[0026], Page 17, [0184], Page 34, [0283] and Fig. 2). Fischer teaches FR1 is a human FR1, CDR1 is a chicken CDR1, FR2 is a human FR2, CDR2 is a chicken CDR2, FR3 is a human FR3, CDR3 is a chicken CDR3, and FR4 is a human FR4 (Page 17, [0184], Page 5, [0025] and Page 3, [0017]).
Fischer does not explicitly teach or suggest the nucleic acid molecule encoding the humanized variable regions of antibodies has a formula of: FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4.
Wu teaches engineering antibodies to reduce the immunogenicity of the antibodies, while maintaining the immune specificity of the antibodies for an antigen (Abstract). Wu teaches creating libraries of antibodies and nucleic acids (Abstract, Page 2, [0016], Page 3, [0023]-[0024] and Page 16, [0076]-[0077]). Wu teaches nucleic acid molecule encoding the humanized variable regions of antibodies has a formula of: FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4 (Page 4, [0026] and Page 16, [0076]). Wu teaches the FR1-4 are human FRs and the CDR1-3 may be non-human and specifically chicken CDRs (Page 15, [0067], Page 34, [0113] and Page 91, [0385]). Wu teaches using these engineered antibodies allows for improved characteristics of the antibody such as improved stability, shelf life, melting temperature, and improved solubility for a pharmaceutical carrier (Page 3, [0020]-[0023]).
It would have been obvious to one having ordinary skill in the art before the effective filing date of the invention to modify the teachings of Fischer with the teachings of Wu to engineer the antibody with the formula FR1-CDR1-FR2-CDR2-FR3-CDR3-FR4. This would allow for improved characteristics of the antibody such as improved stability, shelf life, melting temperature, and solubility for a pharmaceutical carrier as taught by Wu (Page 3, [0020]-[0023]).
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JESSICA DANIELLE PARISI whose telephone number is (571)272-8025. The examiner can normally be reached Mon - Friday 7:30-5:00 Eastern with alternate Fridays off.
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/JESSICA D PARISI/Examiner, Art Unit 1684
/HEATHER CALAMITA/Supervisory Patent Examiner, Art Unit 1684
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