DETAILED ACTION
Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
Examiner’s Comment
The claims have been amended (10/07/2025) to recite different DR5-binding domain variable heavy and light chain regions (VH and VL, respectively) CDR sequences. However, the different sequences only represent CDRs of the same antibody using different numbering schemes and do not change the fact that the same antibody VH and VL comprise the CDR sequences recited in the claims filed 3/31/2025, which claims were examined for the previous Office action. That is, while previously the CDR sequences were identified using the IMGT® scheme, the CDR sequences of the current claims were identified using the Common numbering scheme but are still from the same antibodies. See Tables below and Tables 1-3 of the specification illustrating the different CDR sequences for the same antibody. The claims are drawn to or require antibodies or polypeptides comprising a pair of VH and VL which comprise the CDRs regardless of numbering scheme.
Tables listing SEQ ID NO: of different CDR numbering schemes for antibodies DR5-01 and DR5-05:
Antibody
DR5-01
HCDR1
Sequence #
HCDR2
Sequence #
HCDR3
Sequence #
LCDR1
Sequence #
LCDR2
Sequence #
LCDR3
Sequence #
IMGT®
13
14
15
16
FAS
17
Kabat
22
23
24
25
26
17
Common
32
14
24
16
FAS
17
Antibody
DR5-05
HCDR1
Sequence #
HCDR2
Sequence #
HCDR3
Sequence #
LCDR1
Sequence #
LCDR2
Sequence #
LCDR3
Sequence #
IMGT®
18
14
19
20
RTS
21
Kabat
27
28
29
30
31
21
Common
33
14
29
20
RTS
21
Table listing SEQ ID NO: of VH and VL of antibodies DR5-01 and DR5-05:
Antibody
VH Sequence #
VL Sequence #
DR5-01
35
37
DR5-05
39
41
Response to Amendment
The rejection of claims 1, 3-6 and 15 and dependent claims 2 and 7 under 35 U.S.C. 112(b) is withdrawn in view of the cancellation of claim 3, amendment to claim 4 further clarifying the claim, amendment to claim 5 removing the broad limitation and word “preferably”, also removed in claim 6, and amendment to claim 15 removing reference to a human. Claim 1 remains rejected.
The rejection of claims 6 and 7 under 35 U.S.C. 112(d) is withdrawn in view of the amendment adding a further limitation to each claim.
The rejection of claim 15 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIJA), first paragraph, is withdrawn in view of the amendment to the claim specifying the diseases or conditions express DR5 and the administration is to a subject in need thereof.
The provisional rejection (A) of claim 8 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 84, 86 and 97 of copending Application No. 17/051,205 (‘205, reference application) is withdrawn in view of the amendment to claim 8 removing reference to sequences of antibody DR5-05. This application has now issued as US Patent No.12,338,289 B2, and new claims are rejected over claims therein.
The provisional rejection (B) of claims 1, 5-8 and 15 on the ground of nonstatutory double patenting as being unpatentable over claim 1-3, 9-14,16 and 22-28 of copending Application No. 17/609,359 is withdrawn in view of the abandonment of the copending application.
The provisional rejection (C) of claim 8 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 53, 55-57, 65 and 66 of copending Application No. 17/774,333 (‘333, reference application) is withdrawn in view of the amendment to claim 8 removing reference to sequences of antibody DR5-05. A rejection over claims of ’333 appears below over new claims.
The provisional rejection (D) of claim 8 on the ground of nonstatutory double patenting as being unpatentable over claims 1, 3, 8, 13-30, 32, 36, 39, 42 and 52-65 of copending Application No. 18/017,241 is withdrawn in view of the abandonment of the copending application.
The rejection (F) of claims 1-8, 10 and 15 on the ground of nonstatutory double patenting as being unpatentable over claims 1-9 of U.S. Patent No. 10,647,774 (‘774) in view of Fox et al. (Expert Opin. Biol. Ther. 10(1):1-18, 2010) is withdrawn in view of Applicant’s argument that the patent is drawn to subject matter that was restricted in and is not claimed in the instant application.
The rejection (G) of claim 8 on the ground of nonstatutory double patenting as being unpatentable over claim 15 of U.S. Patent No. 10,882,913 (‘913) is withdrawn in view of the amendment to claim 8 removing reference to sequences of antibody DR5-05. A rejection over claims of ’913 appears below over new claims.
The rejection (H) of claim 8 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6 and 10 of U.S. Patent No. 12,247,080 (‘080) is withdrawn in view of the amendment to claim 8 removing reference to sequences of antibody DR5-05. A rejection over claims of ’080 appears below over new claims.
Claim Interpretation
Claim 19 recites “A bispecific antibody, or a fragment thereof, having the capability to bind to DR5,..” and goes on to describe the antibody, including two different antigen-binding domains thereof. There is no requirement for the fragment to comprise the two different antigen-binding domains since one antigen-binding domain meets the limitations of a fragment, including being capable of binding DR5 as prescribed by the preamble.
Claim Objections
Claims 1 and 5 are objected to because of the following informalities: In claim 1, the first occurrence of “VH” and “VL” should be accompanied by their full names, e.g., variable heavy and variable light chain domain [0065]. In claim 5, “is/are Fv, Fab, F(ab’)2, antibody” does not have an article such as “a” before the first noun.
Appropriate correction is required.
Claim Rejections - 35 USC § 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.
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.
Claim 1 remains and dependent claims 2 and 7 and new claims 18 and 20 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 1 has been amended to recite “at least one polypeptide” and remains indefinite. As written in lines 4-12, the at least one polypeptide comprises a first binding domain and a second binding domain. This means at least one polypeptide comprises both a first and second binding domain. There may be other polypeptides in the composition that also bind DR5. As a result, at least one polypeptide comprising both immunoglobulin binding domains is required. However, the composition cannot comprise only two polypeptides, wherein one (the first) comprises the first binding domain and another (the second) comprises a second binding domain, although it may ‘additionally’ or ‘further’ comprise two separate polypeptides, each comprising one of the binding domains. That “the at least one polypeptide comprises both immunoglobulin binding domains” does not mean it is limited to “one polypeptide” comprising both, but limited only to “at least one polypeptide” comprising both (i.e., there could be more than one polypeptide comprising both). Therefore, the section beginning 4 lines from the end is confusing.
Claims 18 and 20 recite the limitation "the composition of claim" in lines 2-3. There is insufficient antecedent basis for this limitation in the claim. Neither claim upon which claim 18 or 20 depends is drawn to or recites a composition. In the interest of compact prosecution, it will be assumed that the method of claims 18 and 20 administer the product of claims 16 and 19, respectively.
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.
Claims 6, 18 and 20 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIJA), first paragraph, because the specification, while being enabling for a method of inducing apoptosis of a tumor cell and/or treating cancer expressing DR5 in a mammal in need thereof, comprising administering to the mammal an effective amount of the VH/VL-containing polypeptide composition of claim 1, biparatopic, bispecific or multivalent antibody of claim 16 or bispecific antibody or fragment thereof of claim 19, which binds specifically a DR5 receptor and is an agonist thereof, i.e., activates DR5, does not reasonably provide enablement for wherein the cancer or tumor cell does not express DR5, wherein the mammal is not in need of treatment, or wherein the antibody or fragment thereof is not a DR5 agonist. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
The instant methods are drawn to induction of apoptosis of a tumor cell and/or treatment of a cancer by administration of the biparatopic, bispecific or multivalent antibody of claim 16 or bispecific antibody or fragment thereof of claim 19 (note the fragment of claim 19 is not required to be bispecific--see “Claim Interpretation” above). The two enablement issues are i) the scope of the tumor cell type affected or cancer to be treated and ii) the scope of the subject being treated.
While anti-DR5 agonist antibodies and TRAIL, the ligand of DR5, have been shown to induce apoptosis of some cancers, these cancers express the receptor to which the antibodies or ligand bind. As reviewed by Fox et al. (Expert Opin. Biol. Ther. 10(1):1-18, 2010, p. 1, bottom paragraph, cited in the PTO-892 mailed 4/8/25), therapeutic development of agents that that activate DR4 (TRAIL-R1) and/or DR5 (TRAIL-R2) “was driven by the relatively restricted expression of TRAIL-R1 and TRAIL-R2 on tumor cells, the ability of TRAIL-R agonists to induce cell death in a variety of tumor cell lines and the additive or synergistic preclinical activity of TRAIL-R agonists in combination with many different chemotherapeutic agents [1,2].” The instant claims require neither that the composition be a DR5 agonist nor that it induce apoptosis of DR5-expressing cells. Further, as seen in cancer information for DR5 (TNFRSF10B) set forth in The Human Protein Atlas (https://www.proteinatlas.org/ENSG00000120889-TNFRSF10B/cancer, 2025, Protein Expression Summary, legend), not all cancers express DR5. “Most cancers displayed weak to moderate cytoplasmic immunoreactivity. A few cases of liver, pancreatic, stomach, endometrial and cervical cancers exhibited strong positivity. A majority of urothelial cancers, malignant lymphomas and gliomas were negative.” Therefore, the claim would be enabled for treating a cancer expressing DR5 but not for other cancers (see for example, Wang et al., J. Immunother. Canc. 9:e002926, 2021, 11 pages plus supplemental material, cited in the IDS filed 1/26/24, especially paragraph bridging pp. 8-9). If the cancer does not express the DR5 receptor, to which the binding domains recited in independent claims 1, 16 and 19 bind, then it is unclear how a DR5-binding polypeptide, antibody or fragment thereof could be used in the method. The polypeptide, antibody or fragment thereof must be agonistic, that is, it must be able to activate DR5 and induce apoptosis of DR5-expressing cells. The products of claims 1, 16 and 19 have no functional limitation aside from specifically binding DR5. The dependent method claims have no further limitation related to the DR5-binding polypeptide, antibody or fragment thereof of the claims from which they depend. In summary, to have a method one skilled in the art can use without undue experimentation commensurate in scope with the claims, the tumour cell and cancer must express DR5 and the DR5-binding polypeptide, biparatopic, bispecific, multivalent antibody or fragment of the bispecific antibody that binds DR5 must be agonistic such that it activates DR5 and induces apoptosis of the DR5-expressing cell.
Finally, the instant claim does not require that the mammal to be treated be in need of such treatment. As the claims are written, the mammal is in need of administration of the antibody or fragment thereof. As a result, the effective amount may not be sufficient to induce apoptosis of the cancer cell or treat the cancer. Also, if the mammal does not have the disease or disorder to be treated, then it cannot be treated.
For the reasons discussed above and including the breath of cancers and tumour cells encompassed by the claims, the paucity of guidance or direction for treating the cells or cancers which do not express DR5 and the activation of which does not lead to treatment with an DR5-binding polypeptide, antibody or fragment thereof of claim 1, 16 and 19, the lack of working examples in the specification with the exception of treating glioma in a xenograft mouse model ((0256]), and the breadth of mammals which can be treated, e.g., those not in need of said treatment, it would require undue experimentation to practice the method commensurate in scope with the claims.
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.
Claims 19, 20, 22 and 23 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 53, 55, 57 and 65 of copending Application No. 17/774,333 (‘333, reference application).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications recite in the claims a method of treating cancer comprising administering an antibody composition binding DR5 and comprising at least one DR5-binding VH/VL pair, wherein the same VH and VL recited in both applications comprise the CDR1-3 sequences of the copending and instant application. Note that instant claim 19 is drawn to a bispecific antibody, or fragment thereof, having the capability to bind DR5. The fragment of the bispecific antibody may be monospecific and, therefore, may comprise only the single VH/VL pair identical to the pair of claims of ‘333. Claims 1, 53(h) and 55 of ‘333 are drawn to a method of treating a disease which is cancer with two antibodies that bind DR5. Both applications have claims designating a DR5-binding antibody as having the CDRs of antibody DR5-05 (defined in instant Tables 1-3 and on p. 54, lines 23-27, of ‘333). Claim 53(h) recites an antibody used in the method has VH and VL CDR1-3 which are identical respectively to SEQ ID NO:18, 14 and 19, and SEQ ID NO:20, RTS and SEQ ID NO:21, i.e., as defined for antibody DR5-05. Additional dependent claim 65 of ‘333 further defines the antibody target.
The VH and VL CDRs of ’333 claim 53(h) are comprised by the instant VH and VL of SEQ ID NO:39 and 41 (antibody DR5-05, which binds DR5). The HCDR1-3 and LCDR1-3 of the claims of the instant and copending application are comprised by these VH and VL. The ‘333 method of using the antibodies anticipates the instant antibody. Application ’333 has no limitation that the first and second antibody of the method must be different. It would have been obvious to have more than a single antibody molecule.
Claims 1, 2, 4-8 and 15 remain and new claims 16-23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 9,611,327 (‘327).
Although the claims at issue are not identical, they are not patentably distinct from each other because both sets of claims are drawn to a DR5-binding polypeptide comprising at least one pair of VH and VL chains. As recited in claim 1 of ‘327, i) the VH contains CDR1-3 of SEQ ID NO:13-15 and the VL contains CDR1-3 of SEQ ID NO:16, FAS, and 17, respectively, and/or ii) the VH contains CDR1-3 of SEQ ID NO:18, 14 and 19 and the VL contains CDR1-3 of SEQ ID NO:20, RTS, and 21, respectively. The VH/VL of i) SEQ ID NO:35/37 and ii) VH/VL of SEQ ID NO:39/41 (claims 4, 7 and 8 of ‘327, and instant claims 2, 17 and 23) comprise these CDRs and those recited in instant claims 1, 8, 16, 19 and 22. Therefore, the antibodies comprising the CDRs are the same, whether or not those CDRs are defined by different numbering schemes. Different antibody configurations such as scFv and monoclonal antibodies are claimed (instant claim 5, ‘327 claim 5). Both claim wherein the antibody is bispecific or a fragment thereof (instant claims 16 and 19, claims 13 and 15 of ‘327). Both claim wherein the composition comprises two polypeptides (instant claim 1 and claim 18 of ‘327). Both documents claim a method for treating cancer, an autoimmune disease, an inflammatory condition, a viral infection or a viral disease by administration of the composition to a mammal, including a man (instant claims 6, 15, 18 and 20, and claims 16-19 of ‘327). For the instant claims, the composition comprising the polypeptide(s) also comprises a pharmaceutically acceptable carrier, diluent or excipient, which is obvious in view of the administration for the method of treatment.
Applicant argues (p. 10 of REMARKS through top of p. 11) that “[T]he ‘327 patent has the same priority date, patent term filing date, and base expiration date as the instant application, as well as 114 days of patent term adjustment.” (emphasis added by Applicant) The Office has not established that issuance of the instant application would effectively extend the life of the patent. Applicant cites MPEP 804(I)(A), which says, "[T]he examiner must determine whether the grant of a second patent would give rise to an unjustified extension of the rights granted in the first patent." (emphasis added by Applicant) In the absence of a showing of an extension of rights by the Office, the rejection cannot be maintained. The argument has been fully considered but is not persuasive. As stated in the Discussion in Allergan (Allergan USA, Inc. V. MSN Labs Priv. Ltd., 111 F.4th 1358, 136 (Fed. Cir. 2024), p. 13, end of first paragraph, see attached Office action Appendix), "But as we alluded in Abbvie, a common priority date does not always guarantee a common expiration date." As to PTA the Court references In re Cellect LLC (81 F. 4th 1216, 2023 USPQ.2d 1011 (Fed. Cir. 2023), p. 14, second paragraph, of Allergan), saying, "ODP for a patent that has received PTA, regardless of whether or not a terminal disclaimer is required or has been filed, must be based on the expiration date of the patent after PTA has been added." (at 1229, emphasis added in Allergan, see also p. 15, first paragraph of Allergan) According to MPEP § 804.02(VI), "As the presence of a terminal disclaimer affects whether the patent is granted an adjustment, it is necessary that the terminal disclaimer be filed in the application in order to accurately determine whether the patent is entitled to a term adjustment." There is no way for the Examiner to know what the PTA will be for the instant application if it issues as a patent nor would it be proper for the Examiner to guess. MPEP § 1701 indicates that Office personnel may not express an opinion regarding the expiration date of any patent.
Applicant cites case law (p. 11, first full paragraph) to set forth the role of a rejection under double patenting and when a terminal disclaimer is required. Applicant concludes that (p. 11, second full paragraph), “The Office has not established on record, with any clarity or evidence (much less with a preponderance of the evidence), that granting the instant application will unjustly extend the period of exclusivity of the '327 patent.” (emphasis added by Applicant). The case law is acknowledged and the argument has been fully considered but is not persuasive. The case law is for double patenting between two patents, not a patent and pending application as the issue here. It is maintained that the ODP rejection is proper for the reasons of record and as recast above addressing the new and amended claims and as discussed here. Further, improper time-wise extension is not the only reason for requiring a terminal disclaimer. 37 CFR 1.321(c)(3) requires that a terminal disclaimer filed to obviate a nonstatutory double patenting rejection based on commonly owned conflicting claims must also include a provision that any patent granted on that application be enforceable only for and during the period that the patent is commonly owned with the application or patent which formed the basis for the rejection. Whether common ownership "should" or "should not" be a requirement is a policy question upon which the Examiner declines to express an opinion. A terminal disclaimer to ensure common ownership at present is a requirement, and one which the Federal Circuit in In re Cellect commented upon favorably ("We also agree with the USPTO that the Board did not err in determining that a risk of separate ownership existed and, even in the absence of separate ownership, that a terminal disclaimer would have been required to ensure common ownership." Id. at 1230).
Applicant refers (end of first full paragraph of p. 11) to Ex Parte Baurin (Appeal 2024-002920 (PTAB Nov. 6, 2024)). The Examiner notes the case is nonprecedential. Further, the application at issue in the ODP of this case was published before the effective filing date of the reference patent and, therefore, the situation is different from that of the instant application, which shares the same effective filing date as the ‘327 patent.
Claims 19, 21, 22 and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9, 14,15, 17, 18 and 20-23 of U.S. Patent No. 10,882,913 (‘913) in view of Fox et al. (Expert Opin. Biol. Ther. 10(1):1-18, 2010, cited in the PTO-892 mailed 04/08/2025).
Both the instant application and patent claim a composition comprising a polypeptide binding DR5 and comprising at least one DR5-binding VH/VL pair, wherein the VH and VL of the patent and instant application comprise the recited CDR sequences for antibody DR5-05 (as defined in instant Tables 1-3 and in Table 1 of ‘913).
Claim 14 of ‘913 is drawn to a composition comprising a first and second antibody that bind human DR5, wherein the second antibody comprises the VH CDR1-3 of SEQ ID NO:10, 2 and 11 and VL CDR1-3 of SEQ ID NO:13, RTS and SEQ ID NO:14, comprised by VH and VL of SEQ ID NO:12 and 15, respectively, which are the same as VH and VL of instant SEQ ID NO:39 and 41, respectively. The second antibody of ‘080 anticipates the bispecific antibody fragment of instant claim 19 and the antibody of instant claims 22 and 23. The fragment of the bispecific antibody may be monospecific and, therefore, may comprise only the single VH/VL pair identical to the pair of claims of ‘913. The patent does not have claims to a method of treatment.
Fox et al. teaches that six monoclonal antibodies that bind TRAIL-R2 (DR5) are in a Phase I or II clinical trial for treatment of several cancers (Table 1 and, e.g., p. 6, col. 1). It would have been obvious to use a DR5-binding antibody comprising the VH and VL of the DR5-05 antibody of ‘913 to kill tumor cells for the treatment of cancer.
Claims 19, 20, 22 and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4-7, 9-11 and 13 of U.S. Patent No. 12,247,080 (‘080).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications claim a composition comprising a polypeptide binding DR5 and comprising at least one DR5-binding VH/VL pair, wherein the same VH and VL of the patent and instant application comprise the respective recited CDR sequences.
Claims 1, 2, 4-7, 9-11 and 13 of ‘080 are drawn to a method of treating a DR5-expressing solid and/or hematological tumor or inducing apoptosis in DR5-expressing tumors comprising administering a first and second antibody that bind human DR5, wherein the second antibody comprises the VH CDR1-3 of SEQ ID NO:10, 2 and 11 and VL CDR1-3 of SEQ ID NO:13, RTS and SEQ ID NO:14, comprised by VH and VL of SEQ ID NO:12 and 15, respectively, which are the same as VH and VL of instant SEQ ID NO:39 and 41, respectively. The second antibody of ‘080 anticipates the bispecific antibody fragment of instant claim 19 and method of claim 20 and the antibody of instant claims 22 and 23. The fragment of the bispecific antibody may be monospecific and, therefore, may comprise only the single VH/VL pair identical to the pair of claims of ‘080.
Claims 19, 20, 22 and 23 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 5, 7-9, 12-14 of U.S. Patent No. 12,338,289 (‘289).
Although the claims at issue are not identical, they are not patentably distinct from each other because both the instant application and patent claim a method of treating cancer by administration of an antibody that binds DR5 and has the same heavy and light chain CDRs of antibody DR5-05 (defined in instant Tables 1-3, and in Table 1 of ‘289), which methods of use anticipate the antibody used therein (instant claims 19, 22 and 23). Note that instant claim 19 is drawn to a bispecific antibody, or fragment thereof, having the capability to bind DR5. The fragment of the bispecific antibody may be monospecific and, therefore, may comprise only the single VH/VL pair identical to the pair of claims of ‘289. Similarly, while the first and second antibodies of the method of ‘289 each have an antigen-binding region, the antibodies’ antigen-binding regions may be identical (dependent claim 6 of ‘289 limits them to being non-identical). It would have been obvious to have more than a single antibody molecule. Instant claims 22 and 23 are drawn specifically to an antibody binding DR5 and having CDRs comprised by the same VH and VL as the antibody of claim 13, section (c), of ‘289.
SEQ ID NO:35 of the instant claims is identical to SEQ ID NO:56 of ‘289 and represents the sequence of the DR5-05 VH. Instant SEQ ID NO:41 is the same as SEQ ID NO:60 of ‘289, the DR5-05 VL. These VH and VL comprise the HCDR1-3 of instant SEQ ID NO:33, 14, 29 and LCDR1-3 of SEQ ID NO: 20, RTS, 21, respectively, and CDRs of section (c) of claim 13 of ‘289.
Claim Suggestions
The following claim suggestions are presented to Applicant for consideration:
It is suggested that in claims 6, 15, 18 and 20, “comprising the administration to” be substituted with an active method step, e.g., “comprising administering to”.
19. A bispecific antibody, or fragment thereof, having the capability to bind to DR5, said antibody comprising a first antigen-binding site that specifically binds to a first epitope of said DR5, this firstantigen-binding site comprising a pair of VH and VL chains, wherein the VH chain contains a CDR1 of sequence SEQ ID NO: 32, a CDR2 of sequence SEQ ID NO: 14 CDR1, a CDR3 of sequence SEQ ID NO: 24; and the VL chain contains a CDR1 of sequence SEQ ID NO: 16, a CDR2 of sequence FAS, a CDR3 of sequence SEQ ID NO: 17, and a second different antigen-binding site that specifically binds to a second epitope of said DR5, this second different antigen-binding site comprising a pair of VH and VL chains, wherein the VH chain contains a CDR1 of sequence SEQ ID NO: 33, a CDR2 of sequence SEQ ID NO: 14, a CDR3 of sequence SEQ ID NO: 29; and the VL chain contains a CDR1 of sequence SEQ ID NO: 20, a CDR2 of sequence RTS, a CDR3 of sequence SEQ ID NO: 21.
Conclusion
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 Claire Kaufman, whose telephone number is (571) 272-0873. Examiner Kaufman can generally be reached Monday through Friday 7am-3:30pm, Eastern Time.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's supervisor, Vanessa Ford, can be reached at (571) 272-0857.
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Claire Kaufman
/Claire Kaufman/
Primary Examiner, Art Unit 1674
December 30, 2025