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
Continued Examination Under 37 CFR 1.114
1. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 7/14/2026 has been entered.
Status of the Claims
2. Claims 1-159 are the original claims filed 3/2/2023. In the Preliminary Amendment of 6/14/2023, claims 3-17, 21-22, 136, and 158 are amended and Claims 23-77, 79-135, 137-157, and 159 are cancelled. In the Response of 3/5/2026, Claims 1-20, 78, 136, and 158 are amended and claims 21-22 are canceled. In the Response of 7/14/2026, claims 1-2, 18 and 136 are amended and new claim 160 is added.
Claims 1-20, 78, 136, 158 and 160 are pending.
The amendments to the claims raise new grounds for rejection.
Priority
3. USAN 18/177,571, filed 03/02/2023, and having 1 RCE-type filing therein, Claims Priority from Provisional Application 63/316,338, filed 03/03/2022.
Information Disclosure Statement
4. As of 8/30/2026, a total of two (2) IDS are filed: 10/27/2023; and 7/14/2026. The corresponding initialed and dated 1449 form is considered and of record.
Withdrawal of Rejection(s)
Claim Rejections - 35 USC § 112(b)
5. The rejection of Claims 1-20, 78, 136, and 158 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is withdrawn in view of the amendment of claim 1 to delete “3E10”.
Rejection Withdrawn-in-part/ Maintained-in-part
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.
Scope of Enablement
6. The rejection of Claim 136 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, is:
withdrawn in part for removing the invention from a method of prevention of the cancers by amending the claims to recite ameliorate or stabilize; and
maintained in part for failing to identify the target antigen that is expressed on the tumors and to which the antibody of claim 1 binds.
Applicants have not responded to the outstanding grounds for rejection. The response is incomplete. Excerpted from the Office Action of 4/14/2026 (p. 6)
“In the absence of a clear and defined antigen to which the claimed antibodies bind, the POSA cannot reasonably practice the method invention without undue experimentation.
The scope of the claims must bear a reasonable correlation with the scope of enablement. See In re Fisher, 166 USPQ 19, 24 (CCPA 1970). "[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.'" Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365 (Fed. Cir. 1997) (quoting In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993)).”
The rejection is maintained.
Rejections Maintained
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 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 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 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 MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. 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 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual 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/apply/applying-online/eterminal-disclaimer.
SEQ ID NO
18/177,571
18/841,356
18/841,043
19/150,521
19/167,684
85 VL
85
125
120
85
85
86 VL
86
126
121
86
86
87 VL
87
127
122
87
87
88 VL
88
128
123
88
88
89 VL
89
129
124
89
89
90 VL
90
130
125
90
90
64 VH
64
104
99
64
64
65 VH
65
105
100
65
65
66 VH
66
106
101
66
66
67 VH
67
107
102
67
67
68 VH
68
108
103
68
68
69 VH
69
109
104
69
69
70 VH
70
110
105
70
70
SEQ ID NO
18/177,571
18/841,356
18/841,043
19/150,521
19/167,684
91 LC
91
131
126
91
91
92 LC
92
132
127
92
92
93 LC
93
133
128
93
93
94 LC
94
134
129
94
94
95 LC
95
135
130
95
95
96 LC
96
136
131
96
96
97 LC
97
137
132
97
97
98 LC
98
138
133
98
98
99 LC
99
139
134
99
1045
100 LC
100
140
135
100
100
101 LC
101
141
136
101
101
102 LC
102
142
137
102
102
71 HC
71
111
106
71
71
72 HC
72
112
107
72
72
73 HC
73
113
108
73
73
74 HC
74
114
109
74
74
75 HC
75
115
110
75
(82)
76 HC
76
116
111
76
(83)
77 HC
77
117
112
77
77
78 HC
78
118
113
78
78
79 HC
79
119
114
79
79
80 HC
80
120
115
80
80
81 HC
81
121
116
81
82 HC
82
122
117
82
82
83 HC
83
123
118
83
83
84 HC
84
124
119
84
84
7. The provisional rejection of Claims 1-20, 78, 136, 158 and 160 on the ground of nonstatutory double patenting as being unpatentable over claims 1-2, 15, 17, 20, 24, 26, and 59 of copending Application No. 18/841,356 (reference application US 20250170259) is maintained for the pending claims. Applicants invocation of M.P.E.P. 804(I)(B)(1) is not ripe in view of the outstanding and new grounds for rejection.
8. The provisional rejection of Claims 1-20, 78, 136, 158 and 160 on the ground of nonstatutory double patenting as being unpatentable over claims 55, 80-86 of copending Application No. 18/841,043 (reference application US 20250161484) is maintained for the pending claims. Applicants invocation of M.P.E.P. 804(I)(B)(1) is not ripe in view of the outstanding and new grounds for rejection.
9. The provisional rejection of Claims 1-20, 78, 136, 158 and 160 on the ground of nonstatutory double patenting as being unpatentable over claims 85-105 of copending Application No. 19/150,521 (reference application) is maintained for the pending claims.
Applicants invocation of M.P.E.P. 804(I)(B)(1) is not ripe in view of the outstanding and new grounds for rejection.
10. The provisional rejection of Claims 1-20, 78, 136, 158 and 160 on the ground of nonstatutory double patenting as being unpatentable over claims 79-87 of copending Application No. 19/167,684 (reference application) is maintained for the pending claims.
Applicants invocation of M.P.E.P. 804(I)(B)(1) is not ripe in view of the outstanding and new grounds for rejection.
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.
Written Description
11. The rejection of Claims 1-20, 78, 136, and 158 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 is maintained.
Applicants allege invoking the decision in Alonso, Enzo and Teva is misplaced with respect to the instant claims drawn to specific structural characteristics; the absence of an adequately described antigen was one factor considered in the overall written description analysis, together with the breadth of the functionally defined claim, the disclosure of only a single antibody species, and the lack of common structural features identifying the claimed genus.
Response to Arguments
The claims drawn to humanized antibodies comprised of any framework modifications for the most generic antibodies comprising a percent variation for a VH and a VL domain are not proscribed by the antigen to which they bind. Loss of binding affinity to the extent of loss in specificity for a antigen for a humanized antibody is review by Dondelinger et al (PTO 892). It is now well-established and documented that non-CDRs residues may play an important role in the binding affinity of the antibody to its antigen, either by making direct contact with the antigen, by affecting the stability or flexibility of the antibody or its antigen-binding loops, or by structuring the CDR loop itself. Indeed, the residues from the framework regions can modulate the conformation of CDRs and therefore affect the binding affinity. These residues were defined and named “Vernier zone residues” and included amino acids located in the framework regions just in the vicinity of the CDR loops (Foote; PTO 892). Finally, non-CDR residues that influence the light and heavy chain variable domain packing and orientation are also critical for the antigen-binding affinity and, surprisingly, were often ignored or neglected.
More recently, Dunbar et al. (PTO 892) further characterized the orientation of the variable domains. Indeed, one particular angle might reflect more than one single possible orientation of the VH and VL. Therefore, they developed a new method to describe more precisely the VH/VL orientations by defining 5 different angles and one distance. They also investigated positions in the VH/VL interface and the residue identities influencing these different angles and distance. They concluded that a particular residue at a specific position might lead to more than one specific VH/VL angle.
This VH/VL angulation influences also the relative position of the CDRs and, consequently, the shape of the paratope. This parameter can therefore have a strong impact on the binding affinity. Indeed, the binding energy between two atoms is a function of their distance following the Lennard-Jones relation. A difference of a few Angstroms can strongly affect the value of the binding free energy. Using right triangle simple trigonometry and assuming a variable region length of 37 Å, a difference of 1◦ between the VL/VH domains causes a displacement of the atoms exposed on the CDR surfaces by about 0.6 Å. The choice of the framework regions for humanization by the CDR grafting technique is therefore of crucial importance to maintain affinity. For example, Nakanishi et al. showed a severe affinity loss of a humanized antibody and restored the original affinity by performing two mutations at the VH/VL interface (PTO 892). Similarly, Bujotzek et al. performed antibody humanizations by selecting human frameworks based on the predicted VH/VL orientation and revealed a correlation between similar angles and affinity of humanized antibodies (PTO 892). This concept of packing angles is a critical aspect of antibody antigen interaction and the residues that modulate the VH/VL orientation have therefore to be considered as elements that introduce further diversity in the paratopes. The angle between the light and heavy chain variable regions have been described. In CDR-grafting or other antibody humanization methods, residues affecting the VL/VH packing angles should be considered in order to restore full binding affinity.
Thus, neither Applicants arguments, nor the amending of the original claims to delete the target antigen for the claimed antibody structures with infinite framework variations, place Applicants in possession of the full scope of humanized antibodies.
The rejection is maintained.
New Grounds for Rejection
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
12. Claim 160 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 160 recites “or antigen binding fragment.” In depending from claims 1 and 136, the recitation is broadening from “or antigen binding fragment thereof.”
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Conclusion
13. No claims are allowed.
14. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Wu Julie can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643
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