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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 07/22/2026 has been entered.
Priority
This application is a U.S. national phase of International Application No. PCT/US2021/030342, filed on 04/30/2021, which claims domestic benefit to US provision application 63/018,440, filed 04/30/2020.
Claim Status
The Amendment, filed on 07/22/2026, is acknowledged in which:
Claims 2-4, 6-30, 45, 49-53, 55-64, 66-68, 70, and 75-77 are canceled.
Claims 1, 42, 54, 65, and 69 are currently amended.
Claims 5, 31, 33-34, 36-38, 71, and 73-74 were previously presented.
Claims 32, 35, 39-41, 43-44, 46-48, and 72 are original.
Claims 1, 5, 31-44, 46-48, 54, 65, 69, and 71-74 are pending in the instant application and are examined on the merits herein.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/22/2026 has been considered by the examiner.
Withdrawn Objections and Rejections
In the office action dated 04/22/2026,
All previous objections and/or rejections regarding claims 17-18, 23-26, 45 and 70 are rendered moot in view of claim cancellations.
1, 5, 31-41, and 65 were rejected under 35 U.S.C. 112(a) as failing to comply with the written description requirement for encompassing a genus of antibody formulations suggesting interchangeability of CDRs and/or unlimited functional claims without sufficient structure. Applicants’ amendments to restrict the respective claims to antibody CDR sequence sets with sufficient written description have overcome the rejections and the rejections are withdrawn.
The following grounds of objections and/or rejections are either maintained or necessitated by applicant’s amendment to the claims. Please note: The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim Rejections - 35 USC § 112(a) (Maintained)
Claims 42-44, 46-48, 54, 69 and 71-74 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.
Regarding independent claims 42, 54, and 69, the instant claims are drawn to molecules with ABCB5 binding affinity comprising twelve antibody VH/VL pairings each with distinctive CDR sets (summarized in the table below).
SEQ ID NOs:
Set
VH
VL
1
1
20
2
2
21
3
3
22
4
4
23
5
6
23
6
7
20
7
8
20
8
13
26
9
14
27
10
15
28
11
16
29
12
17
28
MPEP 2163(II)(A)(3)(a)(ii) states that the written description requirement for claimed genus may be satisfied through a sufficient description of a representative number of species by actual reduction to practice, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the inventor was in possession of the claimed genus.
As discussed in the previous office action, the instant specification discloses 6 species of CDR sets with evidence of ABCB5 binding (FIGs 2, 15-17), summarized below with corresponding VH/VL species (i.e. embodiments with sufficient written description):
SEQ ID NOs:
Clone
HCDR1
HCDR2
LCDR3
LCDR1
LCDR2
LCDR3
VH
VL
42
55
64
71
75
78
81
13
26
43
55
64
71
76
78
81
14
27
44
55
65
71
80
78
81
15
28
45
56
64
72
80
78
81
16
29
100
49
57
66
73
77
79
5
22
101
55
64
71
80
78
81
17
28
Of these six clones, several additional clones with 100% CDR identity (i.e. identical critical binding paratope with variation only framework residues) have VH/VL pairings that would likely maintain binding to ABCB5 (summarized in the table below):
SEQ ID NOs:
HCDR1
HCDR2
LCDR3
LCDR1
LCDR2
LCDR3
VH
VL
49
57
66
73
77
79
1
20
49
57
66
73
77
79
4
22
49
57
66
73
77
79
8
20
The content at issue and failing to comply with written description requirements are additional VH/VL pairings (i.e. SEQ ID NOs: 2 and 21; 3 and 22; 4 and 23; 6 and 23; 7 and 20) comprising unique CDR sequences without evidence of ABCB5 binding affinity.
The state of the art near the effective filing date of the claimed invention demonstrates that antibody functionality is dependent on amino acid structure, particularly regarding complementarity of the six CDRs. It is understood by one of ordinary skill in the art that mutations to CDRs are unpredictable and that each construct requires function testing.
Rabia (Biochem Eng J. 2018 Sep 15;137:365-374.) teaches that antibody-antigen binding specificity is primarily mediated by their CDRs within the sequences of variable heavy and variable light chains (Introduction, ¶ 1). Given the chemical diversity possible within combined CDRs alone (~20 different amino acids at ~60 sites), not all combinations can result in viable antibodies suitable for therapeutic applications. Rabia et al. teaches that natural antibody maturation relies on random somatic mutations followed by clonal selection for antibodies with improved affinity and/or with mutations that compensate for destabilizing affinity enhancing mutations (page 366, column 2, ¶ 2). However, it is expected that most somatic mutations that increase affinity, such as those that increase hydrophobicity or charge, can also reduce specificity. For instance, arginine in CDRs was identified as the greatest risk factor for non-specific interactions (page 368, column 1, ¶ 5). Based on these teachings, introducing mutations in antibody structure, particularly in the CDR regions, requires thorough testing to ensure suitable binding specificity and antibody stability.
Furthermore, even though some of the non-tested CDR combinations may differ in only one amino acid residue, Koenig (PNAS USA. 2017;114(4):E486-E495) teaches that single amino acid mutations across both VL and VH can alter stability and antibody-antigen binding. In generating a single mutation library in VL and VH chains (Figure 1), Koenig et al. identified mutations distal to CDRs can improve anti-VEGF antibody G6.31 stability (anti-gD tag; enriched in red) and affinity (VEGF; enriched in red), but conserved framework positions including the hydrophobic core and interface residues in addition to a few CDR positions, particularly in HCDR3, exhibited low tolerance to mutation (depleted in blue/ strongly depleted in black). Therefore, even a single residue difference could result in loss of antibody stability and/or binding.
Based on prior art, making changes to the CDR sequences of an antibody is a highly unpredictable process and one skilled in the art could not a priori make any predictions regarding changing residues with any reasonable expectation of success nor envisage the breadth of CDR combinations as claimed that would still possess claimed ABCB5 binding without functional testing. As such, an ordinarily skilled artisan would not have recognized that applicant was in possession of the entire scope of the claimed genus at the time of the effective filing date of the claimed invention. Therefore, instant claims 42, 54, and 69, and subsequent dependent claims 43-44, 46-48 and 71-74 that do not rectify the issues as discussed above were found to not meet the written description requirement of 35 USC 112(a).
Conclusion
Claims 1, 5, 31-41, and 65 are allowable and claims 42-44, 46-48, 54, 69 and 71-74 are rejected.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HANNAH SUNSHINE whose telephone number is (571)270-7417. The examiner can normally be reached M-Th & Second Friday 8:30am-5pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama can be reached at (571) 272-2911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/HANNAH SUNSHINE/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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