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 .
DETAILED ACTION
The amendment filed August 25, 2026 in response to the Office Action of June 29, 2026 is acknowledged and has been entered.
Claims 1, 6, 8, 13, 14, 19, 21, and 60 have been amended.
Claims 9, 10, 22, 23, 25, 32 and 33 have been cancelled.
Claims 67-71 have been added.
Claims 1, 5, 6, 8, 11-15, 18, 19, 21, 60, and 67-71 are pending and under consideration.
In view of the amendments in the drawings and the Specification, the objection to the numbering of the figures is hereby withdrawn. However, the objection to the drawing executed in color is maintained, because no petition has been filed and granted.
In view of amendments in the Sequence Listing and the Specification, the objection to Nucleotide and/or Amino Acid Sequence Disclosures is hereby withdrawn
In view of cancellation of claims 9, 23, and 33, the 112(b) rejection is hereby withdrawn.
In view of cancellation of claims 9, 10, 22, 23, 25, 32 and 33, and amendments of claims 6 and 19, the 112(a) rejection set forth in the Office Action of June 29, 2026 is hereby withdrawn.
In view of claim 14 amendment, the 102 set forth in the Office Action of June 29, 2026 is hereby withdrawn.
Claim Interpretation
Claims 1 and 14 recite: “at least first and second structurally distinct antibodies or antibody fragments, wherein said first antibody or antibody fragment has heavy and light chain CDR1-3 sequences of SEQ ID NOS: 5-7 and 8-10, respectively, wherein said second antibody or antibody fragment has heavy and light chain CDR1-3 sequences of SEQ ID NOS: 15-17 and 18-20, respectively, wherein said first antibody comprises a wild-type IgG1 Fc region and said second antibody comprises a LALA mutated IgG1 Fc region”. Given Broadest Reasonable Interpretation (BRI), the recited first antibody fragment may not have a wild-type IgG1 Fc region, and the recited second antibody fragment may not have a LALA mutated IgG1 Fc region, as evidenced by instant claims 8 and 21, and paragraph [0141] of instant publication US 2024/0287160. Thus, antibody fragments with the recited HCDR1-3 and LCDR1-3 would read on said first antibody or antibody fragment or said second antibody or antibody fragment.
It is also noted that the term “delivering” a composition (e.g. antibody, RNA, DNA or vector) was interpreted as “administering” a composition.
Drawings
Color photographs and color drawings are not accepted in utility applications unless a petition filed under 37 CFR 1.84(a)(2) is granted. Any such petition must be accompanied by the appropriate fee set forth in 37 CFR 1.17(h), one set of color drawings or color photographs, as appropriate, if submitted via the USPTO patent electronic filing system or three sets of color drawings or color photographs, as appropriate, if not submitted via the via USPTO patent electronic filing system, and, unless already present, an amendment to include the following language as the first paragraph of the brief description of the drawings section of the specification:
The patent or application file contains at least one drawing executed in color. For example, the brief description of the figures describes different colors for Figs. 3A-C, 4A-C, 5A-B, 6A-F, 8A-C, 9A-C, 10, 13, however no color drawings were submitted. Copies of this patent or patent application publication with color drawing(s) will be provided by the Office upon request and payment of the necessary fee.
Color photographs will be accepted if the conditions for accepting color drawings and black and white photographs have been satisfied. See 37 CFR 1.84(b)(2).
Claim Objections
Claim 60 is objected to because of the following informalities: “method of claim 1” should be “The method of claim 1”. Appropriate correction is required.
MAINTAINED/MODIFIED REJECTIONS
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 14, 18, 19, 21, and 71 are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by Crowe (Crowe et al., WO 2020/014443 A1, Publication Date: 01/16/2020, cited in IDS of 11/15/2024).
As set forth above, given BRI, the recited first antibody fragment may not have a wild-type IgG1 Fc region, and the recited second antibody fragment may not have a LALA mutated IgG1 Fc region, as evidenced by instant claims 8 and 21, and paragraph [0141] of instant publication US 2024/0287160. Because EBOV-442 comprises the recited first antibody fragment and EBOV-51 comprises the recited second antibody fragment, scFv derived from EBOV-442 and scFv derived from EBOV-515, which do not comprise a Fc domain, still read on the amended claims 14, 18, 19 and 21.
Crowe teaches that EBOV-442 and EBOV-515 potently neutralize EBOV and BDBV (the bridging paragraph of pages 96-97). As evidenced by paragraphs [0082] -[0085] of the instant publication US 2024/0287160 A1, EBOV-442 comprises a heavy chain and light chain of SEQ ID NO: 3 and SEQ ID NO: 4, respectively; EBOV-515 comprises a heavy chain and light chain of SEQ ID NO: 13 and SEQ ID NO: 14, respectively (also see Table 2 of Crowe). Crowe also teaches treating a subject with ebolavirus with an antibody from Table 2 and fragments thereof, such as scFv (claims 11-13, 17 and 20). Thus, as set forth above, the fragments thereof read on the instant claims 14, 18, and 19, because they comprise recited antibody fragments.
Crowe teaches that EBOV-442 can enhance the binding of EBOV-515 to intact GP ~3 to 5-fold. Such a cooperative binding effect could facilitate recognition of intact GP by broadly neutralizing mAbs in polyclonal plasma or therapeutic antibody mixtures. (Fig. 5E, and page 101, para. 2).
Crowe teaches that combination therapy with a cocktail of several potent mAbs has been considered necessary for treatment of ebolavirus infections (the bottom paragraph of page 107).
Crowe teaches that cocktails are preferred for prevention or treatment of viral infections to accomplish breadth of coverage against diverse virus species and to prevent emergence of antibody escape mutant virus (page 132, para. 2).
Crowe teaches various antibodies for ebolavirus listed in Table 2 (page 5, lines 21-25).
Crowe teaches vaccine formulation comprising one or more antibodies or fragments thereof from Table 2 (the bridging paragraph of pages 6-7, claims 47 and 51). It is noted that Table 2 discloses 21 antibodies, including EBOV-442 (on page 154) and EBOV-515 (on page 156). Thus, Crowe teaches a vaccine formulation comprising antibody fragments derived from EBOV-442 and EBOV-515.
Regarding claim 21, Crowe teaches that at least one of said antibody fragments is a recombinant scFv (single chain fragment variable) antibody (claims 12, 20, 32, 43, 53, 68 and 86).
Regarding claim 71, Crowe teaches the composition of instant claim 14. In addition, Crowe teaches that the DNA sequences encoding EBOV-442 light chain (SEQ ID NO: 6) and heavy chain (SEQ ID NO: 5); EBOV-515 light chain (SEQ ID NO: 24) and heavy chain (SEQ ID NO: 23). As shown below: SEQ ID NO: 5 of Crowe is 100% identical to SEQ ID NO: 1 of the instant claim; SEQ ID NO: 6 of Crowe is 100% identical to SEQ ID NO: 2 of the instant claim; SEQ ID NO: 23 of Crowe is 99.6% identical to SEQ ID NO: 11 of the instant claim; SEQ ID NO: 24 of Crowe is 100% identical to SEQ ID NO: 12 of the instant claim.
SEQ ID NO: 5 of Crowe alignment with SEQ ID NO: 1 of the instant claim:
SEQ ID NO: 5 of Crowe is identical to SEQ ID NO: 1 of the instant claim:
Query Match 100.0%; Score 408; Length 408;
Best Local Similarity 100.0%;
Matches 408; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GAGGTGCAGTTGGTGGAGTCTGGGGGAGGCCTCGTAAAGCCGGGGGGGTCCCTTAGACTC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GAGGTGCAGTTGGTGGAGTCTGGGGGAGGCCTCGTAAAGCCGGGGGGGTCCCTTAGACTC 60
Qy 61 TCCTGTACAGGCTCTGGAGGCACTGGATTCACTTTCAAGTATGCCGGGATGAGCTGGGTC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TCCTGTACAGGCTCTGGAGGCACTGGATTCACTTTCAAGTATGCCGGGATGAGCTGGGTC 120
Qy 121 CGCCAGGCTCCAGGGAAGGGGCCGGAGTGGATTGGCCGTATTAAAAGCAGGATTGATGGT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 CGCCAGGCTCCAGGGAAGGGGCCGGAGTGGATTGGCCGTATTAAAAGCAGGATTGATGGT 180
Qy 181 GGGACAACAGACTACGCTGCACCCGTGAAAGACAGATTCATTGTCTCAAGAGATGATTCA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GGGACAACAGACTACGCTGCACCCGTGAAAGACAGATTCATTGTCTCAAGAGATGATTCA 240
Qy 241 AGAAATACACTCTATCTGCAAATGAACAGCCTGAAGACCGAGGACACAGCCGTCTATTAT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 AGAAATACACTCTATCTGCAAATGAACAGCCTGAAGACCGAGGACACAGCCGTCTATTAT 300
Qy 301 TGTGCCACAGGATCGGGAAAGGGGCCCTCTGCGTCGTTCGGGGAGTCATACTACTACTAC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 TGTGCCACAGGATCGGGAAAGGGGCCCTCTGCGTCGTTCGGGGAGTCATACTACTACTAC 360
Qy 361 GACTTCATTAACGTCTGGGGCAAAGGGACCACGGTCACCGTCTCCTCA 408
||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GACTTCATTAACGTCTGGGGCAAAGGGACCACGGTCACCGTCTCCTCA 408
SEQ ID NO: 6 of Crowe alignment with SEQ ID NO: 2 of the instant claim:
Query Match 100.0%; Score 324; Length 324;
Best Local Similarity 100.0%;
Matches 324; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GAAAGTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GAAAGTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACC 60
Qy 61 CTCTCGTGCAGGGCCAGTCAGAGTATTAGCAGGAAGTACTTAGCCTGGTACCAGCAGAAA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 CTCTCGTGCAGGGCCAGTCAGAGTATTAGCAGGAAGTACTTAGCCTGGTACCAGCAGAAA 120
Qy 121 CCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTTCATCCAGCAGGGCCACTGGCATCCCA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 CCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTTCATCCAGCAGGGCCACTGGCATCCCA 180
Qy 181 GACAGATTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GACAGATTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAG 240
Qy 241 CCTGAAGATTTTGCAGTGTATTACTGTCATCAGTATGAAAGCTCACCTTGGACGTTCGGC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CCTGAAGATTTTGCAGTGTATTACTGTCATCAGTATGAAAGCTCACCTTGGACGTTCGGC 300
Qy 301 CAAGGGACTAAGGTGGAAATCAAA 324
||||||||||||||||||||||||
Db 301 CAAGGGACTAAGGTGGAAATCAAA 324
SEQ ID NO: 23 of Crowe alignment with SEQ ID NO: 11 of the instant claim:
Query Match 99.6%; Score 364.4; Length 366;
Best Local Similarity 99.7%;
Matches 365; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 CAGGTGCAGCTGCACGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTC 60
|||||||||||||| |||||||||||||||||||||||||||||||||||||||||||||
Db 1 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTC 60
Qy 61 ACCTGCACTGTCTCTGGTGGGTCCATCAACAGTGCTGGTTACTACTGGACCTGGATCCGC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ACCTGCACTGTCTCTGGTGGGTCCATCAACAGTGCTGGTTACTACTGGACCTGGATCCGC 120
Qy 121 CAGCACCCGGGGAAGGGCCTGGAGTGGATTGGGTACATCGATTATACTGGGAGGACCTAC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 CAGCACCCGGGGAAGGGCCTGGAGTGGATTGGGTACATCGATTATACTGGGAGGACCTAC 180
Qy 181 TACAACCCGTCCCTTGAGAGCCGAGTGATCATTTCAATAGACACGTCTAAGAACCACTTC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TACAACCCGTCCCTTGAGAGCCGAGTGATCATTTCAATAGACACGTCTAAGAACCACTTC 240
Qy 241 TCCCTGAGACTGACCTCTGTGTCTGCCGCGGACACGGCCGTGTATTACTGTGCGCGAGAA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TCCCTGAGACTGACCTCTGTGTCTGCCGCGGACACGGCCGTGTATTACTGTGCGCGAGAA 300
Qy 301 TCGTCGTGGGTATCCGAGTTAGGGCGTGACAACTGGGGCCAGGGAACCCTGGTCACCGTC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 TCGTCGTGGGTATCCGAGTTAGGGCGTGACAACTGGGGCCAGGGAACCCTGGTCACCGTC 360
Qy 361 TCTTCA 366
||||||
Db 361 TCTTCA 366
SEQ ID NO: 24 of Crowe alignment with SEQ ID NO: 12 of the instant claim:
Query Match 100.0%; Score 321; Length 321;
Best Local Similarity 100.0%;
Matches 321; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GAAATAGTGATGACGCAGTCTCCAGCCACCCTGCCTGTGTCTCCAGGGGAAGGAGCCACC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GAAATAGTGATGACGCAGTCTCCAGCCACCCTGCCTGTGTCTCCAGGGGAAGGAGCCACC 60
Qy 61 CTCTCCTGCAGGGCCAGTCAGAGTGTTTTCACCAACTTAGCCTGGTACCAGCAAAAACCT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 CTCTCCTGCAGGGCCAGTCAGAGTGTTTTCACCAACTTAGCCTGGTACCAGCAAAAACCT 120
Qy 121 GGCCAGGCTCCCAGGCTCCTCATCTATGATGCATCCACCAGGGCCACTGGTATCCCAGCC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GGCCAGGCTCCCAGGCTCCTCATCTATGATGCATCCACCAGGGCCACTGGTATCCCAGCC 180
Qy 181 AGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 AGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCT 240
Qy 241 GAAGACTTTGCAGTTTATTATTGTCAGCAGTATAATAACTGGCCTCGGACGTACGGCCAA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GAAGACTTTGCAGTTTATTATTGTCAGCAGTATAATAACTGGCCTCGGACGTACGGCCAA 300
Qy 301 GGGACCAGGGTGGAAGTCAAA 321
|||||||||||||||||||||
Db 301 GGGACCAGGGTGGAAGTCAAA 321
Claim Rejections - 35 USC § 103
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 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, 5, 6, 8, 11-13, 15, 60, and 67-70 are rejected under 35 U.S.C. 103 as being unpatentable over Crowe (Crowe et al., WO 2020/014443 A1, Publication Date: 01/16/2020, cited in IDS of 11/15/2024), as applied to claims 14, 18, 19, 21, and 71 above.
Examiner’s Note: the term “delivering” an antibody was interpreted as “administering” an antibody.
Crowe teaches the composition of the instant claim 14, as set forth above.
In addition, Crowe teaches that filovirus entry is a complex process involving cathepsin-mediated cleavage of GP into GP intermediate (lines 1-2 on page 99). Antibodies EMOV-442, -515 and -520 inhibited cleavage in a dose-dependent manner. EBOV-442 was the most efficient mAb and completely inhibited GP cleavage at 0.3 μM (page 99, lines25-31).
Crowe teaches EBOV-437 and EBOV-442, which are glycan cap-specific mAbs that recognize all three pathogenic ebolaviruses and do not compete for binding with the base region specific mAbs, such as EBOV-515. Antibody EBOV-442 appears to be an optimal partner for enhancing the activity of the base region antibodies. EBOV-442 potently neutralize EBOV, BDBV and to a lesser extent SUDV, partially protected mice from lethal EBOV challenge, exhibited multiple effector functions in in vitro assays, efficiently inhibited GP cleavage in vitro, and cooperated in binding with EBOV-515. EBOV-442 appears to be promising candidate for inclusion in a combination therapy with EBOV-515 or EBOV-520 as a next-generation therapeutic antibody cocktail for ebolavirus treatment (page 108, lines 19-30).
Crowe teaches a method of treating a subject infected with ebolavirus or reducing the likelihood of infection of a subject at risk of contracting ebolavirus, comprising delivering to the antibodies of Table 2 (claims 13 and 17).
Crowe teaches as set forth above. However, Crowe does not teach delivering the claimed antibody cocktail/combination to a subject for the claimed method. It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to administer EBOV-442 (or scFV derived from EBOV-442) and EBOV-515 (or scFv derived from EBOV-515) (e.g. the vaccine comprising EBOV-442 and EBOV-515) for treating a subject infected with ebolavirus or reducing the likelihood of infection of ebolavirus because Crowe teaches using both antibodies for treating ebola virus . One of ordinary skill in the art would have had a reasonable expectation that administering EBOV-442 (or scFV derived from EBOV-442) and EBOV-515 (or scFv derived from EBOV-515) can enhance the therapeutic activity compared to single antibody treatment, because Crowe teaches that both 1) antibodies (or scFv) can be used to treat a subject infected with ebolavirus or to reduce the likelihood of infection of a subject at risk of contracting ebolavirus; 2) both EBOV-442 and EBOV-515 can potently neutralize EBOV; 3) EBOV-442 does not compete for binding with the base region specific mAb EBOV-515; 4) EBOV-442 can enhance the binding of EBOV-515 to intact GP ~3 to 5-fold; 5) EBOV-442 is an optimal partner for enhancing the activity of the base region antibodies; 6) combination therapy with a cocktail of several potent mAbs has been considered necessary for treatment of ebolavirus infections; 7) vaccine formulation comprising antibodies: EBOV-442 (or scFV derived from EBOV-442) and EBOV-515 (or scFv derived from EBOV-515). The motivation would have been to develop a better treatment for ebolavirus related conditions.
Regarding claim 8, Crowe teaches that said antibody fragment is a recombinant scFv (single chain fragment variable) antibody, Fab fragment, F(ab')2 fragment, or Fv fragment (claim 20).
Regarding claims 11 and 12, Crowe teaches that said antibody or antibody fragment is administered prior to infection or after infection (claim 23). It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to treat a subject diagnosed with an ebolavirus infection (after infection) with the antibody cocktail, because the cocktail can be used to subject infected with ebolavirus.
Regarding claim 13, Crowe teaches wherein delivering comprises antibody or antibody fragment administration, or genetic delivery with an RNA or DNA sequence or vector encoding the antibody or antibody fragment (claim 25).
Regarding claims 15, and 68-70, Crowe teaches the composition of instant claim 14. In addition, Crowe teaches that the DNA sequences encoding EBOV-442 light chain (SEQ ID NO: 6) and heavy chain (SEQ ID NO: 5); EBOV-515 light chain (SEQ ID NO: 24) and heavy chain (SEQ ID NO: 23). As shown below: SEQ ID NO: 5 of Crowe is 100% identical to SEQ ID NO: 1 of the instant claim; SEQ ID NO: 6 of Crowe is 100% identical to SEQ ID NO: 2 of the instant claim; SEQ ID NO: 23 of Crowe is 99.6% identical to SEQ ID NO: 11 of the instant claim; SEQ ID NO: 24 of Crowe is 100% identical to SEQ ID NO: 12 of the instant claim.
SEQ ID NO: 5 of Crowe alignment with SEQ ID NO: 1 of the instant claim:
SEQ ID NO: 5 of Crowe is identical to SEQ ID NO: 1 of the instant claim:
Query Match 100.0%; Score 408; Length 408;
Best Local Similarity 100.0%;
Matches 408; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GAGGTGCAGTTGGTGGAGTCTGGGGGAGGCCTCGTAAAGCCGGGGGGGTCCCTTAGACTC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GAGGTGCAGTTGGTGGAGTCTGGGGGAGGCCTCGTAAAGCCGGGGGGGTCCCTTAGACTC 60
Qy 61 TCCTGTACAGGCTCTGGAGGCACTGGATTCACTTTCAAGTATGCCGGGATGAGCTGGGTC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 TCCTGTACAGGCTCTGGAGGCACTGGATTCACTTTCAAGTATGCCGGGATGAGCTGGGTC 120
Qy 121 CGCCAGGCTCCAGGGAAGGGGCCGGAGTGGATTGGCCGTATTAAAAGCAGGATTGATGGT 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 CGCCAGGCTCCAGGGAAGGGGCCGGAGTGGATTGGCCGTATTAAAAGCAGGATTGATGGT 180
Qy 181 GGGACAACAGACTACGCTGCACCCGTGAAAGACAGATTCATTGTCTCAAGAGATGATTCA 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GGGACAACAGACTACGCTGCACCCGTGAAAGACAGATTCATTGTCTCAAGAGATGATTCA 240
Qy 241 AGAAATACACTCTATCTGCAAATGAACAGCCTGAAGACCGAGGACACAGCCGTCTATTAT 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 AGAAATACACTCTATCTGCAAATGAACAGCCTGAAGACCGAGGACACAGCCGTCTATTAT 300
Qy 301 TGTGCCACAGGATCGGGAAAGGGGCCCTCTGCGTCGTTCGGGGAGTCATACTACTACTAC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 TGTGCCACAGGATCGGGAAAGGGGCCCTCTGCGTCGTTCGGGGAGTCATACTACTACTAC 360
Qy 361 GACTTCATTAACGTCTGGGGCAAAGGGACCACGGTCACCGTCTCCTCA 408
||||||||||||||||||||||||||||||||||||||||||||||||
Db 361 GACTTCATTAACGTCTGGGGCAAAGGGACCACGGTCACCGTCTCCTCA 408
SEQ ID NO: 6 of Crowe alignment with SEQ ID NO: 2 of the instant claim:
Query Match 100.0%; Score 324; Length 324;
Best Local Similarity 100.0%;
Matches 324; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GAAAGTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GAAAGTGTGTTGACGCAGTCTCCAGGCACCCTGTCTTTGTCTCCAGGGGAAAGAGCCACC 60
Qy 61 CTCTCGTGCAGGGCCAGTCAGAGTATTAGCAGGAAGTACTTAGCCTGGTACCAGCAGAAA 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 CTCTCGTGCAGGGCCAGTCAGAGTATTAGCAGGAAGTACTTAGCCTGGTACCAGCAGAAA 120
Qy 121 CCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTTCATCCAGCAGGGCCACTGGCATCCCA 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 CCTGGCCAGGCTCCCAGGCTCCTCATCTATGGTTCATCCAGCAGGGCCACTGGCATCCCA 180
Qy 181 GACAGATTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAG 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 GACAGATTCAGTGGCAGTGGGTCTGGGACAGACTTCACTCTCACCATCAGCAGACTGGAG 240
Qy 241 CCTGAAGATTTTGCAGTGTATTACTGTCATCAGTATGAAAGCTCACCTTGGACGTTCGGC 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 CCTGAAGATTTTGCAGTGTATTACTGTCATCAGTATGAAAGCTCACCTTGGACGTTCGGC 300
Qy 301 CAAGGGACTAAGGTGGAAATCAAA 324
||||||||||||||||||||||||
Db 301 CAAGGGACTAAGGTGGAAATCAAA 324
SEQ ID NO: 23 of Crowe alignment with SEQ ID NO: 11 of the instant claim:
Query Match 99.6%; Score 364.4; Length 366;
Best Local Similarity 99.7%;
Matches 365; Conservative 0; Mismatches 1; Indels 0; Gaps 0;
Qy 1 CAGGTGCAGCTGCACGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTC 60
|||||||||||||| |||||||||||||||||||||||||||||||||||||||||||||
Db 1 CAGGTGCAGCTGCAGGAGTCGGGCCCAGGACTGGTGAAGCCTTCACAGACCCTGTCCCTC 60
Qy 61 ACCTGCACTGTCTCTGGTGGGTCCATCAACAGTGCTGGTTACTACTGGACCTGGATCCGC 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 ACCTGCACTGTCTCTGGTGGGTCCATCAACAGTGCTGGTTACTACTGGACCTGGATCCGC 120
Qy 121 CAGCACCCGGGGAAGGGCCTGGAGTGGATTGGGTACATCGATTATACTGGGAGGACCTAC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 CAGCACCCGGGGAAGGGCCTGGAGTGGATTGGGTACATCGATTATACTGGGAGGACCTAC 180
Qy 181 TACAACCCGTCCCTTGAGAGCCGAGTGATCATTTCAATAGACACGTCTAAGAACCACTTC 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 TACAACCCGTCCCTTGAGAGCCGAGTGATCATTTCAATAGACACGTCTAAGAACCACTTC 240
Qy 241 TCCCTGAGACTGACCTCTGTGTCTGCCGCGGACACGGCCGTGTATTACTGTGCGCGAGAA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 TCCCTGAGACTGACCTCTGTGTCTGCCGCGGACACGGCCGTGTATTACTGTGCGCGAGAA 300
Qy 301 TCGTCGTGGGTATCCGAGTTAGGGCGTGACAACTGGGGCCAGGGAACCCTGGTCACCGTC 360
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 301 TCGTCGTGGGTATCCGAGTTAGGGCGTGACAACTGGGGCCAGGGAACCCTGGTCACCGTC 360
Qy 361 TCTTCA 366
||||||
Db 361 TCTTCA 366
SEQ ID NO: 24 of Crowe alignment with SEQ ID NO: 12 of the instant claim:
Query Match 100.0%; Score 321; Length 321;
Best Local Similarity 100.0%;
Matches 321; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 GAAATAGTGATGACGCAGTCTCCAGCCACCCTGCCTGTGTCTCCAGGGGAAGGAGCCACC 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 GAAATAGTGATGACGCAGTCTCCAGCCACCCTGCCTGTGTCTCCAGGGGAAGGAGCCACC 60
Qy 61 CTCTCCTGCAGGGCCAGTCAGAGTGTTTTCACCAACTTAGCCTGGTACCAGCAAAAACCT 120
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 CTCTCCTGCAGGGCCAGTCAGAGTGTTTTCACCAACTTAGCCTGGTACCAGCAAAAACCT 120
Qy 121 GGCCAGGCTCCCAGGCTCCTCATCTATGATGCATCCACCAGGGCCACTGGTATCCCAGCC 180
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 121 GGCCAGGCTCCCAGGCTCCTCATCTATGATGCATCCACCAGGGCCACTGGTATCCCAGCC 180
Qy 181 AGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCT 240
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 181 AGGTTCAGTGGCAGTGGGTCTGGGACAGAGTTCACTCTCACCATCAGCAGCCTGCAGTCT 240
Qy 241 GAAGACTTTGCAGTTTATTATTGTCAGCAGTATAATAACTGGCCTCGGACGTACGGCCAA 300
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 241 GAAGACTTTGCAGTTTATTATTGTCAGCAGTATAATAACTGGCCTCGGACGTACGGCCAA 300
Qy 301 GGGACCAGGGTGGAAGTCAAA 321
|||||||||||||||||||||
Db 301 GGGACCAGGGTGGAAGTCAAA 321
Although Crowe does not teach the exact same DNA sequence of SEQ ID NO: 11, it would have been prima facie obvious at the time the invention was made to generate the nucleic acids encoding the therapeutic antibodies taught by Crowe because disclosure of the polypeptide makes the nucleic acid encoding the protein obvious as the methods of obtaining the nucleic acids are routine in the art and can be obtained with a reasonable expectation of success. See MPEP 2143(E)(Example 3), Ex parte Kubin, 83 USPQ2d 1410 (Bd. Pat. App. & Int. 2007), and In re Kubin 90 USPQ2d 1417 (U. S. Court of Appeals Fed. Cir. 2009).
Regarding claim 60, Crowe teaches the composition of instant claim 14. Crowe further teaches a method of protecting the health of a placenta and/or fetus of a pregnant a subject infected with or at risk of infection with ebolavirus comprising delivering to said subject an antibody of Table 2 (page 7, para. 3; claims 61, 66). Thus, It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to use the combination of EBOV-442 and EBOV-515 for the claimed method for enhancing the therapeutic efficacy of the treatment. Given the teachings from Crowe, one of ordinary skill in the art would have had a reasonable expectation of success because EBOV-442 can enhance EBOV-515 ebolavirus neutralizing activity. The motivation would have been to develop a better treatment.
Response to Arguments
For the rejections under 35 U.S.C. §102 and §103, Applicant mainly argues:
First, applicant notes that claims 22 and 23 have been canceled, rendering the rejection as it is applied to these claim moot. Second, claim 14 has been amended to recite "wherein said first antibody comprises a wild-type IgG1 Fc region and said second antibody comprises a LALA mutated IgG1 Fc region." Crowe et al. fails to disclose such a composition. As such, the anticipation rejection is overcome, reconsideration and withdrawal of which are therefore respectfully requested.
Applicant’s arguments have been fully considered but they are not persuasive. As set forth above, given BRI, the amended claims encompass antibody fragment which may not comprise the recited IgG1 Fc region for the first antibody and second antibody. Thus, scFV derived from EBOV-442 and scFv derived from EBOV-515, which do not comprise a FC domain, would still read the amended claims as set forth above, because EBOV-442 (or scFV derived from EBOV-442) comprises the first antibody fragment has heavy and light chain CDR1-3 sequences of SEQ ID NOS: 5-7 and 8-10, respectively; EBOV-515 (or scFv derived from EBOV-515) comprise the second antibody fragment has heavy and light chain CDR1-3 sequences of SEQ ID NOS: 15-17 and 18-20. Thus, the 102 rejection is maintained for the reasons of record.
For 103 rejection, applicant further argues that based on the results of Example 2, the specific combination of rEBOV-442 (with a wild-type Fc region) and rEBOV-515 (with a LALA mutated Fc region) cocktail shows synergistic activity. This finding is unexpected because another cocktail rEBOV-520 and rEBOV-548 does not show this synergistic activity.
Applicant’s arguments have been fully considered but they are not persuasive. As set forth above, the claims are not limited to this configuration, instead the claims encompass antibody fragments without Fc regions, or antibody variants with different heavy chain and light chain. Thus, the example is not commensurate in scope.
The evidence of nonobviousness must be commensurate in scope with the claims to rebut the prima facie case of obviousness. See MPEP 716.02 (d). Thus, the evidence provided with the specific cocktail of rEBOV-442 and rEBOV-515 is not sufficient to overcome the obviousness rejection because the claims are not limited to the specific combination. In view of the foregoing, when all of the evidence is considered, the totality of the rebuttal evidence of nonobviousness fails to outweigh the evidence of obviousness.
NEW REJECTIONS
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 69 and 70 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 69 recites the limitation "the method of claim 14" in line 1. There is insufficient antecedent basis for this limitation in the claim. For examination purpose, the claim is interpretated as “the method of claim 1”.
Claim 70 recites the limitation "the method of claim 14" in line 1. There is insufficient antecedent basis for this limitation in the claim. For examination purpose, the claim is interpretated as “the method of claim 1”.
Conclusion
No claims are allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CHENG LU whose telephone number is (571)272-0334. The examiner can normally be reached Monday-Friday 8-5.
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/CHENG LU/ Examiner, Art Unit 1642
/PETER J REDDIG/ Primary Examiner, Art Unit 1646
