Detailed Office Action
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Status of the Claims
Acknowledgement is hereby made of receipt and entry of the communication filed 02 July, 2024. Claims 1-23 were canceled without prejudice or disclaimer and new claims 24-33 submitted.
37 C.F.R. § 1.98
The information disclosure statements filed 02 July, 2024, have been placed in the application file and the information referred to therein has been considered.
37 C.F.R. § 1.84
Acknowledgement is hereby made of receipt and entry of the drawings filed on 02 July, 2024, which are deemed to be acceptable. The petition to accept color drawings filed under 37 C.F.R. § 1.84(a)(2) has been granted.
37 C.F.R. § 1.52
The specification is objected to because it is illegible (e.g., see Table 3, p. 28; Table 4, p. 29; Table 7, pp. 33-37; Table 8, pp. 37-41). Applicants are reminded that the specification (including the abstract and claims), and any amendments for applications, except as provided for in 37 C.F.R. § 1.821 through 1.825, must have text written plainly and legibly either by a typewriter or machine printer in a nonscript type font (e.g., Arial, Times Roman, or Courier, preferably a font size of 12) lettering style having capital letters which should be at least 0.3175 cm. (0.125 inch) high, but may be no smaller than 0.21 cm. (0.08 inch) high (e.g., a font size of 6) in portrait orientation and presented in a form having sufficient clarity and contrast between the paper and the writing thereon to permit the direct reproduction of readily legible copies in any number by use of photographic, electrostatic, photo-offset, and microfilming processes and electronic capture by use of digital imaging and optical character recognition; and only a single column of text. See 37 C.F.R. § 1.52(a) and (b). Legible replacement pages in compliance with 37 C.F.R. § 1.52(a) and (b) and § 1.125 is/are required.
37 C.F.R. § 1.821-1.825
Summary of Requirements for Patent Applications Filed On Or After July 1, 2022, That Have Sequence Disclosures
37 C.F.R. § 1.831(a) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 C.F.R. § 1.831(b) must contain a "Sequence Listing XML", as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 C.F.R. § 1.831-1.835. This "Sequence Listing XML" part of the disclosure may be submitted:
1. In accordance with 37 C.F.R. § 1.831(a) using the symbols and format requirements of 37 C.F.R. § 1.832 through 1.834 via the USPTO’s patent electronic filing system (Patent Center) (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/patents-application-process/filing-online/legal-framework-efs-web), hereinafter "Legal Framework") in XML format, together with an incorporation by reference statement of the material in the XML file in a separate paragraph of the specification (an incorporation by reference paragraph) as required by 37 C.F.R. § 1.835(a)(2) or 1.835(b)(2) identifying:
a. the name of the XML file
b. the date of creation; and
c. the size of the XML file in bytes; or
2. In accordance with 37 C.F.R. § 1.831(a) using the symbols and format requirements of 37 C.F.R. § 1.832 through 1.834 on read-only optical disc(s) as permitted by 37 C.F.R. § 1.52(e)(1)(ii), labeled according to 37 C.F.R. § 1.52(e)(5), with an incorporation by reference statement of the material in the XML format according to 37 C.F.R. § 1.52(e)(8) and 37 C.F.R. § 1.835(a)(2) or 1.835(b)(2) in a separate paragraph of the specification identifying:
a. the name of the XML file;
b. the date of creation; and
c. the size of the XML file in bytes.
This application contains sequence disclosures that are encompassed by the definitions for nucleotide and/or amino acid sequences set forth in 37 C.F.R. § 1.821(a)(1) and (a)(2) (e.g., see Table 3, p. 28; Table 4, p. 29). However, this application fails to comply with the requirements of 37 C.F.R. § 1.821 through 1.825. Applicants are reminded that the sequence rules embrace all unbranched nucleotide sequences with ten or more bases and all unbranched, non-D amino acid sequences with four or more amino acids, provided that there are at least 4 “specifically defined” nucleotides or amino acids. The rules apply to all sequences in a given application, whether claimed or not. All such sequences are relevant for the purposes of building a comprehensive database and properly assessing prior art. It is therefore essential that all sequences, whether only disclosed or also claimed, be included in the database. See 37 C.F.R. § 1.821(a) and M.P.E.P. § 2421.02.
Specific deficiency-Sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 C.F.R. § 1.821(d) (e.g., see Table 3, p. 28; Table 4, p. 29). Applicant must provide:
- A substitute specification in compliance with 37 C.F.R. § 1.121(b)(3) and 1.125 inserting the required sequence identifiers, consisting of:
- A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
- A copy of the amended specification without markings (clean version); and
- A statement that the substitute specification contains no new matter.
35 U.S.C. § 101
The following is a quotation of 35 U.S.C. § 101 which reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter or any new and useful improvement thereof, may obtain a patent therefore, subject to the conditions and requirements of this title.
Section 33(a) of the America Invents Act reads as follows:
Notwithstanding any other provision of law, no patent may issue on a claim directed to or encompassing a human organism.
Claim 32 is rejected under 35 U.S.C. § 101 and section 33(a) of the America Invents Act as being directed to or encompassing a human organism. See also Animals - Patentability, 1077 Off. Gaz. Pat. Office 24 (April 21, 1987) (indicating that human organisms are excluded from the scope of patentable subject matter under 35 U.S.C. § 101). The claim is directed toward a cell comprising the expression vector of claim 29. The specification discusses the utilization of expression vectors to express the claimed antibodies (see pp. 20-21). These constructs could be utilized to express VRC01-like antibodies within a patient. Thus, the cells would be wholly integrated into the human being and inseparable therefrom. The scope of the claim, therefore, encompasses a human being, which is non-statutory subject matter. Amendment of the claim language to reference “non-human” or “isolated/purified” cells would obviate the rejection.
35 U.S.C. § 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.
Claims 24-33 are rejected under 35 U.S.C. § 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention. Two separate requirements are set forth under this statute: (1) the claims must set forth the subject matter that applicants regard as their invention; and (2) the claims must particularly point out and distinctly define the metes and bounds of the subject matter that will be protected by the patent grant.
The claims reference an isolated anti-CD4 binding site (anti-CD4bs) VRC01-related antibody comprising the recited variable heavy and light chain regions, wherein said heavy chain comprises a substitution at target amino acid position 54, wherein said numbering is based upon the Kabat system. This particular claim limitation is vague and indefinite. The specification states that preferred mutations include G54W, G54F, and G54Y in NIH45-46 (p. 11 and Fig. 15A). However, examination of the VRC01 heavy chain sequence (SEQ ID NO.: 2) fails to reveal Gly at amino acid position 54. According to the Kabat numbering scheme this position contains Arg and position 55 contains Gly. Dondelinger et al. (2018) discuss some of the limitations associated with antibody numbering. Thus, it would not be readily manifest to the skilled artisan which amino acid should be targeted for modification in any given antibody. Appropriate clarification is required.
Kabat Numbering NIH45-46 VH (SEQ ID NO.: 6)
Heavy Chain
Q
V
R
L
S
Q
S
G
G
Q
M
K
K
P
G
E
S
M
R
L
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
S
C
R
A
S
G
Y
E
F
L
N
C
P
I
N
W
I
R
L
A
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
P
G
R
R
P
E
W
M
G
W
L
K
P
R
G
G
A
V
N
Y
41
42
43
44
45
46
47
48
49
50
51
52
53
53A
54
55
56
57
58
59
A
R
K
F
Q
G
R
V
T
M
T
R
D
V
Y
S
D
T
A
F
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
L
E
L
R
S
L
T
S
D
D
T
A
V
Y
F
C
T
R
G
K
80
81
82
82A
82B
82C
83
84
85
86
87
88
89
90
91
92
93
94
95
96
Y
C
T
A
R
D
Y
Y
N
W
D
F
E
H
W
G
R
G
A
P
97
98
99
100
100A
100B
100C
100D
100E
100F
100G
100H
101
102
103
104
105
106
107
108
V
T
V
S
S
109
110
111
112
113
Kabat Numbering VRC01 VH (SEQ ID NO.: 2)
Heavy Chain
Q
V
Q
L
V
Q
S
G
G
Q
M
K
K
P
G
E
S
M
R
I
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
S
C
R
A
S
G
Y
E
F
I
D
C
T
L
N
W
I
R
L
A
21
22
23
24
25
26
27
28
29
30
31
32
33
34
35
36
37
38
39
40
P
G
K
R
P
E
W
M
G
W
L
K
P
R
G
G
A
V
N
Y
41
42
43
44
45
46
47
48
49
50
51
52
53
54
55
56
56A
57
58
59
A
R
P
L
Q
G
R
V
T
M
T
R
D
V
Y
S
D
T
A
F
60
61
62
63
64
65
66
67
68
69
70
71
72
73
74
75
76
77
78
79
L
E
L
R
S
L
T
V
D
D
T
A
V
Y
F
C
T
R
G
K
80
81
82
82A
82B
82C
83
84
85
86
87
88
89
90
91
92
93
94
95
96
N
C
D
Y
N
W
D
F
E
H
W
G
R
G
T
P
V
I
V
S
97
98
99
100
100A
100B
100C
100D
101
102
103
104
105
106
107
108
109
110
111
112
S
113
CDRs are highlighted in colors (CDR1, CDR2, CDR3).
The green letters indicate heavy chain region while the blue letters indicate light chain region.
Moreover, the reference to a substitution at position 54 is also vague and indefinite because it fails to identify the original amino acid at this position and the nature of the substitution. Thus, the skilled artisan cannot readily ascertain if any given antibody has been modified at this location. Amendment of the claim language to reference a G54W, G54F, or G54Y mutation in the heavy chain would be acceptable.
Nonstatutory Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 U.S.P.Q.2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 U.S.P.Q.2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 U.S.P.Q. 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 U.S.P.Q. 761 (C.C.P.A. 1982); In re Vogel, 422 F.2d 438, 164 U.S.P.Q. 619 (C.C.P.A. 1970); and In re Thorington, 418 F.2d 528, 163 U.S.P.Q. 644 (C.C.P.A. 1969).
A timely filed terminal disclaimer in compliance with 37 C.F.R. § 1.321(c) or § 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See M.P.E.P. § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in M.P.E.P. § 2159. See M.P.E.P. §§ 706.02(l)(1)-706.02(l)(3) for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 C.F.R. § 1.321(b).
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 24-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 9,890,207 B2 (issued 13 February, 2018). Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the instant application are directed toward an isolated anti-CD4 binding site (anti-CD4bs) VRC01-related antibody that comprises a substitution at amino acid position 54 in the variable heavy chain. Preferred antibodies include the heavy and light chains set forth in SEQ ID NOS.: 1-46. Nucleic acids and expression vectors encoding the claimed antibodies are also set forth. The ‘207 patent discloses compositions comprising VRC01 variants comprising modifications at amino acid position 54. Accordingly, the claims are not patentably distinct.
Claims 24-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 9,493,549 B2 (issued 15 November, 2016). Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the instant application are directed toward an isolated anti-CD4 binding site (anti-CD4bs) VRC01-related antibody that comprises a substitution at amino acid position 54 in the variable heavy chain. Preferred antibodies include the heavy and light chains set forth in SEQ ID NOS.: 1-46. Nucleic acids and expression vectors encoding the claimed antibodies are also set forth. The ‘549 patent discloses compositions comprising VRC01 variants comprising modifications at amino acid position 54. Accordingly, the claims are not patentably distinct.
Claims 24-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 9,879,068 B2 (issued 30 January, 2018). Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the instant application are directed toward an isolated anti-CD4 binding site (anti-CD4bs) VRC01-related antibody that comprises a substitution at amino acid position 54 in the variable heavy chain. Preferred antibodies include the heavy and light chains set forth in SEQ ID NOS.: 1-46. Nucleic acids and expression vectors encoding the claimed antibodies are also set forth. The ‘068 patent discloses compositions comprising VRC01 variants comprising modifications at amino acid position 54. Accordingly, the claims are not patentably distinct.
Claims 24-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. 11,149,081 B2 (issued 19 October, 2021). Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the instant application are directed toward an isolated anti-CD4 binding site (anti-CD4bs) VRC01-related antibody that comprises a substitution at amino acid position 54 in the variable heavy chain. Preferred antibodies include the heavy and light chains set forth in SEQ ID NOS.: 1-46. Nucleic acids and expression vectors encoding the claimed antibodies are also set forth. The ‘081 patent discloses compositions comprising VRC01 variants comprising modifications at amino acid position 54. Accordingly, the claims are not patentably distinct.
Claims 24-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 10,590,187 B2 (issued 17 March, 2020). Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the instant application are directed toward an isolated anti-CD4 binding site (anti-CD4bs) VRC01-related antibody that comprises a substitution at amino acid position 54 in the variable heavy chain. Preferred antibodies include the heavy and light chains set forth in SEQ ID NOS.: 1-46. Nucleic acids and expression vectors encoding the claimed antibodies are also set forth. The ‘187 patent discloses compositions comprising VRC01 variants comprising modifications at amino acid position 54. Accordingly, the claims are not patentably distinct.
Claims 24-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 11,472,868 B2 (issued 18 October, 2022). Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the instant application are directed toward an isolated anti-CD4 binding site (anti-CD4bs) VRC01-related antibody that comprises a substitution at amino acid position 54 in the variable heavy chain. Preferred antibodies include the heavy and light chains set forth in SEQ ID NOS.: 1-46. Nucleic acids and expression vectors encoding the claimed antibodies are also set forth. The ‘868 patent discloses nucleic acids and expression vectors encoding VRC01 variants comprising modifications at amino acid position 54. Accordingly, the claims are not patentably distinct.
Claims 24-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 12,173,052 B2 (issued 24 December, 2024). Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the instant application are directed toward an isolated anti-CD4 binding site (anti-CD4bs) VRC01-related antibody that comprises a substitution at amino acid position 54 in the variable heavy chain. Preferred antibodies include the heavy and light chains set forth in SEQ ID NOS.: 1-46. Nucleic acids and expression vectors encoding the claimed antibodies are also set forth. The ‘052 patent discloses compositions comprising VRC01 variants comprising modifications at amino acid position 54. Accordingly, the claims are not patentably distinct.
Claims 24-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3 of U.S. Patent No. 12,054,538 B2 (issued 06 August, 2024). Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the instant application are directed toward an isolated anti-CD4 binding site (anti-CD4bs) VRC01-related antibody that comprises a substitution at amino acid position 54 in the variable heavy chain. Preferred antibodies include the heavy and light chains set forth in SEQ ID NOS.: 1-46. Nucleic acids and expression vectors encoding the claimed antibodies are also set forth. The ‘538 patent discloses methods for producing compositions comprising VRC01 variants comprising modifications at amino acid position 54. Accordingly, the claims are not patentably distinct.
Claims 24-33 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6 of U.S. Patent No. 12,173,052 B2 (issued 24 December, 2024). Although the claims at issue are not identical, they are not patentably distinct from each other. The claims of the instant application are directed toward an isolated anti-CD4 binding site (anti-CD4bs) VRC01-related antibody that comprises a substitution at amino acid position 54 in the variable heavy chain. Preferred antibodies include the heavy and light chains set forth in SEQ ID NOS.: 1-46. Nucleic acids and expression vectors encoding the claimed antibodies are also set forth. The ‘052 patent discloses compositions comprising VRC01 variants comprising modifications at amino acid position 54. Accordingly, the claims are not patentably distinct.
Correspondence
Any inquiry concerning this communication should be directed to Jeffrey S. Parkin, Ph.D., whose telephone number is (571) 272-0908. The Examiner can normally be reached Monday through Friday from 10:00 AM to 6:00 PM. A message may be left on the Examiner's voice mail service. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice. If attempts to reach the Examiner are unsuccessful, the Examiner's supervisor, Michael Allen, Ph.D., can be reached at (571) 270-3497. Direct general status inquiries to the Technology Center 1600 receptionist at (571) 272-1600.
Information regarding the status of an application may be obtained from the Patent Center. Status information for published applications may be obtained from the Patent Center. Status information for unpublished applications is available through the Patent Center for authorized users only. Should you have questions about access to Patent Center, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
Respectfully,
/JEFFREY S PARKIN/Primary Examiner, Art Unit 1671 29 September, 2026
