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 .
Election/Restrictions
Applicant’s election without traverse of Group I, claims 1-24 and 29, in the reply filed on 10/1/2025 is acknowledged.
Claims 25-28 and 30-34 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 10/1/2025.
Specification/Sequence Listing
The replacement sequence listing submitted 5/5/2023 is acknowledged.
The substitute specification filed 8/11/2023 has been entered.
The disclosure is objected to because of the following informalities:
The incorporation of sequence listing on page 1 of the specification should reference the size of the file in bytes not kilobytes (KB). See MPEP 2422.03(I). See page 1 of substitute specification filed 8/11/2023.
Appropriate correction is required.
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 1-24 and 29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Tanokura et al. (WO 2020/116398, of record) and are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Tanokura et al. (WO 2020/116398, of record), Tanokura et al. (U.S. Patent Application Publication 2022/0033485, of record), and Tanokura et al. (U.S. Patent No. 12,227,563).
The applied references have a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Tanokura et al. (U.S. Patent Application Publication 2022/0033485, of record) has inventorship Tanokura, Kato, Eguchi, Takagi, Yamamura, Nimiki, Ishikawa, Higuchi, Takeo, and Ohori which is by other than the inventorship of the instant application (Matsukawa, Eguchi, Namiki, and Tanokura). U.S. Patent Application Publication 2022/0033485 has an effective filing date of 2 December 2019 which is prior to the filing date of PCT/JP2021/020890 (1 June 2021) and JP 2020-096344 (2 June 2020), the priority document in the instant application. In addition, applicant cannot rely upon the certified copy of the foreign priority application JP 2020-096344 to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216. The effective filing date of the instant application is 1 June 2021. Tanokura et al. is valid prior art under 35 USC 102(a)(2).
Tanokura et al. (WO 2020/116398, of record) is in Japanese but is the equivalent of U.S. Patent Application Publication 2022/0033485. WO 2020/116398 was published 11 June 2020 and filed 2 December 2019. It is valid prior art under 35 USC 102(a)(1) and 35 USC 102(a)(2).
Tanokura et al. (U.S. Patent No. 12,227,563) issued from application 17/299,383 (a 371 application of PCT/JP2019/047050 which published as WO 2020/116398). It is the equivalent of U.S. Patent Application Publication 2022/0033485 and valid prior art under 35 USC 102(a)(2).
Tanokura et al. (U.S. Patent Application Publication 2022/0033485) will be referenced.
Tanokura et al. (U.S. Patent Application Publication 2022/0033485, of record) discloses humanized anti-IGF-1 receptor antibodies based on antibody IGF11-16. At least one CDR had a substitution relative to antibody IGF11-16. See at least paragraphs [0158 and 0167] and Example 1. Pharmaceutical compositions are disclosed. See at least 14 of Tanokura et al. with respect to instant claim 29.
SEQ ID NO: 1, 2, 3, 4, 5, and 6 of Tanokura et al. are identical to instant SEQ ID NO: 1, 3, 7, 9, 11, and 13, respectively. These CDR sequences are identical to the mouse parent antibody of IGF11-16. See the CDRs of SEQ ID NOS: 85-90, respectively, on page 19 of the instant specification.
The humanized IGF-1R antibodies in claim 1 of Tanokura et al. meet the limitations of instant claims 1 and 3 as claim 1 of Tanokura et al. recites that one amino acid substitution can be made in CDR-H1 and CDRL-2 as well as one or two amino acid substitutions can be made in CDR-H2, CDR-H3, CDR-L1, and CDR-L3 for the VH CDRs of SEQ ID NOS: 1, 2, and 3 and for the VL CDRs of SEQ ID NOS: 4, 5, and 6. That is, the humanized IGF-1R antibodies in claim 1 of Tanokura et al. permits changes in the CDRs which would then differ from those in the instant claims as recited. Substitution of a single amino acid in one or more CDRs (as permitted by claim 1 of Tanokura et al.) would provide antibodies meeting the limitations of instant claims 4-5.
With respect to instant claim 2, the VH of SEQ ID NO: 7 has a proline at amino acid position 25. See at least claims 2-3 of Tanokura et al.
With respect to instant claim 6, at least claim 6 discloses these limitations. Instant SEQ ID NO: 71 corresponds to SEQ ID NO: 14 and contains amino acids 308-319 of the human IGF-1 receptor.
With respect to instant claim 7, the Tanokura et al. antibody with a VH of SEQ ID NO: 7 with CDR substitutions permitted by claim 1 and VL of SEQ ID NO: 8 with CDR substitutions permitted by claim 1 meet the limitations of instant claim 7 for a VH of SEQ ID NO: 55 and a VL of SEQ ID NO: 67. See claim 2 of Tanokura et al. as it depends upon claim 1.
Alignment of SEQ ID NO: 7 (Qy) with instant SEQ ID NO: 55 (Db) with the VH CDRs underlined. SEQ ID NO: 7 has homology of 90% or more to instant SEQ ID NO: 55. With a mutation in any CDR, this VH would still have homology of 90% or more to instant SEQ ID NO: 55 and meet the limitations of instant claim 7.
Query Match 92.0%; Score 573; DB 1; Length 117;
Best Local Similarity 90.6%;
Matches 106; Conservative 5; Mismatches 6; Indels 0; Gaps 0;
Qy 1 QVQLVQPGAELVKPGASVKVSCKAPGYTFTSYWMHWVRQAPGQGLEWIGETNPSNSVTNY 60
|||||| |||: |||||||||||||||||||||||||||||||||||:||||||||||||
Db 1 QVQLVQSGAEVKKPGASVKVSCKAPGYTFTSYWMHWVRQAPGQGLEWMGETNPSNSVTNY 60
Qy 61 NEKFKSKATLTVDTSTSTVYMELSSLRSEDTAVYYCTIGRGRGFAYWGQGTLVTVSS 117
:||: : |||||||||| ||||||||||||||||||||||||||||||||||||||
Db 61 AQKFQGRVTLTVDTSTSTAYMELSSLRSEDTAVYYCTIGRGRGFAYWGQGTLVTVSS 117
Alignment of SEQ ID NO: 8 (Qy) with instant SEQ ID NO: 67 (Db). SEQ ID NO: 8 has homology of 90% or more to instant SEQ ID NO: 67. With a mutation in any CDR, this VL would still have homology of 90% or more to instant SEQ ID NO: 67 and meet the limitations of instant claim 7.
Query Match 96.8%; Score 547; DB 1; Length 107;
Best Local Similarity 96.3%;
Matches 103; Conservative 1; Mismatches 3; Indels 0; Gaps 0;
Qy 1 DIQMTQSPSSLSASVGDRVTITCRASQNINFWLSWYQQKPGKAPKLLIYKASNLHTGVPS 60
|||||||||||||||||||||||||||||||||||||||||| |||||||||||||||||
Db 1 DIQMTQSPSSLSASVGDRVTITCRASQNINFWLSWYQQKPGKVPKLLIYKASNLHTGVPS 60
Qy 61 RFSGSGSGTDFTFTISSLQPEDIATYYCLQGQSYPYTFGQGTKLEIK 107
|||||||||||| |||||||||:|||||||||||||||| |||||||
Db 61 RFSGSGSGTDFTLTISSLQPEDVATYYCLQGQSYPYTFGGGTKLEIK 107
With respect to instant claims 8-10, at least claims 4-5 and paragraphs [0113, 0133, and 0136] disclose these limitations. With respect instant claim 11, at least paragraph [0115] discloses this limitation. With respect to instant claims 12-13 and 19-20, at least claim 7 and paragraphs [0068, 0088-0090, 0118, 0135-0145, 0155-0156] disclose the limitations of these claims. With respect to instant claim 15, at least paragraphs [0139-0141 and 0205-0211] disclose these limitations. With respect to instant claim 17, at least claim 8 discloses these limitations. With respect to instant claim 18, at least claim 9 discloses these limitations.
With respect to instant claim 14, the properties recited in this claim are considered to be inherent to the antibodies of Tanokura et al. based on the binding information disclosed. Tanokura et al. does not disclose testing with a BIACORE binding assay.
The antibodies of Tanokura et al. meet the structural limitations of instant claim 1. As such, the properties of claims 16 and 21-24 are considered to be inherent to the antibodies of Tanokura et al. See in addition paragraphs [0146 and 0175]. Tanokura et al. does not disclose inducing hypophysectomized model animals, proliferation induced by IGF-1 receptor activating ligands, cancer cell proliferation assays, or cancer-bearing model animals.
Applicant is reminded that the instant claims are directed to products and not methods of using products. Should applicant provide argument or evidence that the properties recited in the claims are not inherent to the antibodies of Tanokura, this will be viewed as an admission that the scope of the claims is not enabled. In addition, applicant should point out those structural features responsible for providing each of the different biological effects recited in the claims.
Claims 1-6, 8-24 and 29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Eguchi et al. (WO 2018/221521, of record) and Eguchi et al. (U.S. Patent Application Publication 2020/0115460, of record) and are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Eguchi et al. (WO 2018/221521, of record), Eguchi et al. (U.S. Patent Application Publication 2022/0115460, of record), and Eguchi et al. (U.S. Patent No. 11,629,194).
The applied references have a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Eguchi et al. (U.S. Patent Application Publication 2020/0155460, of record) has inventorship Eguchi, Tanokura, Takagi, Kato, Yamamura, and Namiki which is by other than the inventorship of the instant application (Matsukawa, Eguchi, Namiki, and Tanokura). U.S. Patent Application Publication 2020/155460 has an effective filing date which is prior to the filing date of PCT/JP2021/020890 (1 June 2021) and JP 2020-096344 (2 June 2020), the priority document in the instant application. In addition, applicant cannot rely upon the certified copy of the foreign priority application JP 2020-096344 to overcome this rejection because a translation of said application has not been made of record in accordance with 37 CFR 1.55. When an English language translation of a non-English language foreign application is required, the translation must be that of the certified copy (of the foreign application as filed) submitted together with a statement that the translation of the certified copy is accurate. See MPEP §§ 215 and 216. The effective filing date of the instant application is 1 June 2021.
Eguchi et al. (WO 2018/221521, of record) is in Japanese but is the equivalent of U.S. Patent Application Publication 2020/0115460.
Eguchi et al. (U.S. Patent No. 11,629,194) issued from application 16/610,396 (a 371 application of PCT/JP2018/020581 which published as WO 2018/221521). It is the equivalent of U.S. Patent Application Publication 2020/0115460.
Eguchi et al. (U.S. Patent Application Publication 2020/0115460) will be referenced.
SEQ ID NO: 3, 4, 5, 6, 7, and 8 of Eguchi et al. are identical to instant SEQ ID NO: 1, 3, 7, 9, 11, and 13, respectively. These CDR sequences are identical to the mouse parent antibody of IGF11-16. See the CDRs of SEQ ID NOS: 85-90, respectively, on page 19 of the instant specification. At least claim 24 is directed to an anti-IGF-1 receptor antibody or its fragment or a derivative having these sequences where one amino acid substitution can be made in CDR-H1 and CDRL-2 as well as one or two amino acid substitutions can be made in CDR-H2, CDR-H3, CDR-L1, and CDR-L3 for the VH CDRs of SEQ ID NOS: 3, 4, and 5 and for the VL CDRs of SEQ ID NOS: 6, 7, and 8. Humanization in the framework regions is also implicit to claim 24 of Eguchi et al. because no particular frameworks are required. Claims 25-26 of Eguchi et al as they depends from claim 24 recite that the framework regions can be from a human immunoglobulin (i.e. a humanized antibody). In addition, while claim 24, does not specifically recite humanization, one would have understood this claim to include humanization based on substitutions in the CDR sequences. See at least paragraphs [0077, 0078-0085, 0109, 0142, and 0170-0174], particularly paragraph [0174]. That is, the IGF-1R antibodies in claim 24 of Eguchi et al. permits changes in the CDRs which would then differ from those in the instant claims as recited and include humanized sequences. Substitution of a single amino acid in one or more CDRs (as permitted by claim 24 of Eguchi et al.) would provide antibodies meeting the limitations of instant claims 4-5.
With respect to instant claim 2, the VH of SEQ ID NO: 9 has a proline at amino acid position 25. See at least claim 27 of Eguchi et al. which permits changes in the CDRs by virtue of the 90% similarity limitations.
With respect to instant claim 6, at least claims 17-18 discloses these limitations. SEQ ID NO: 32 in claim 18 corresponds to amino acids 308-319 of instant SEQ ID NO: 71.
With respect to instant claims 8-10, at least claims 25-26 and paragraph [0143] disclose these limitations.
With respect instant claim 11, at least claim 11 and paragraphs [0077 and 0144] disclose this limitation.
With respect to claim 29, pharmaceutical compositions are disclosed. See at least claim 33.
With respect to instant claims 12-24, see at least claims 7-14, 16-17 and 21-22 and paragraph [0077, 0097-0098, 0116-0118]. The antibodies of Eguchi et al. meet the structural limitations of instant claim 1. As such, the properties of claims 12-24 are considered to be inherent to the antibodies of Eguchi et al. where the disclosure in Eguchi et al. does not use the identical language as in the instant claims. Applicant is reminded that the instant claims are directed to products and not methods of using products. Should applicant provide argument or evidence that the properties recited in the claims are not inherent to the antibodies of Eguchi et al., this will be viewed as an admission that the scope of the claims is not enabled. In addition, applicant should point out those structural features responsible for providing each of the different biological effects recited in the claims.
Claims 1, 11, 19-24, and 29 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Singh et al. (WO 03/106621, of record).
Singh et al. discloses antagonistic anti-IGF-1 receptor humanized antibodies and fragments thereof. VH CDRs of SEQ ID NOS: 1-3 and VL CDRs of SEQ ID NOS: 4-6 are disclosed. A humanized VH of SEQ ID NO: 13 and a humanized VL sequences of SEQ ID NOS: 9-12 are disclosed. The antibodies can be used to inhibit the grown of a cancer cell. Pharmaceutical compositions are disclosed. The humanized antibodies had improved affinity for the IGF-1 receptor. See at least claims 1, 22-24, 30-35, and 55, and paragraphs [0021, 0024-0025, 0156-0157].
At least for example, SEQ ID NO: 13 contains instant SEQ ID NO: 85 at amino acid positions 31-35. However, there are differences between the CDR of SEQ ID NO: 2 and instant SEQ ID NO: 86 and the CDR of SEQ ID NO: 3 and instant SEQ ID NO: 87. (SEQ ID NOS: 85, 86, and 87 are the heavy chain CDRs for antibody IGF11-16.
Alignment of SEQ ID NO: 2 (Qy) and instant SEQ ID NO: 86:
Qy 1 EINPSNGRTNYNEKFKQ 17
| |||| ||||||||
Db 1 ETNPSNSVTNYNEKFKS 17
Alignment of SEQ ID NO: 3 (Qy) and instant SEQ ID NO: 86:
Qy 1 GRPDYYGSSKWYFDV 15
||
Db 1 GRGRGFAY 8
SEQ ID NO: 13 with CDRs underlined:
QVQLVQSGAEVVKPGASVKLSCKASGYTFTSYWMWVKQRPGQGLEWIGEINPSNGRTNYNQKFQGKATLTVDKSSSTAYMQLSSLTSEDSAVYYFARGRPDYYGSSKWYFDVWGQGTTVTVSS
These antibodies are considered to meet the limitations of instant claim 1 as the humanized VH and VL sequences have at least one of the CDRs that contains a substitution of at least one amino acid relative to the corresponding CDR of the mouse parent antibody IGF11-16. Instant claim 1 does not require any particular framework sequences and permits unlimited substitutions in the CDRs.
With respect to claims 11 and 19-24, the antibodies of Singh et al. meet the structural requirements of the claims and absent evidence to the contrary, the properties recited in claims 19-24 would be inherent.
Applicant is reminded that the instant claims are directed to products and not methods of using products. Should applicant provide argument or evidence that the properties recited in the claims are not inherent to the antibodies of Singh et al., this will be viewed as an admission that the scope of the claims is not enabled. In addition, applicant should point out those structural features responsible for providing each of the different biological effects recited in the claims.
Claim Rejections - 35 USC § 112
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 1-24 and 29 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.
The specification does not provide an adequate description for the genus of antibodies embraced by the claims.
The specification discloses the VH of SEQ ID NOS: 43 (VH13_PN) , 47 (VH13_PS), 49 (VH23_PN), 53 (VH23_PS), 55(VH25_PN), and 59 (VH25_PS) and the VL of SEQ ID NOS: 65 (VL22), 67 (VL23), and 69 (VL24). See instant claim 7 and page 27. Specific combinations of these VH/VL are disclosed in Figures 1A-F.
The VH of SEQ ID NOS: 47, 53, and 59 have the CDRs of SEQ ID NOS: 85, 5, and 87. The VH of SEQ ID NOS: 43, 49, and 55 have the CDRs of SEQ ID NOS: 85, 5, and 87, where the sixth position of SEQ ID NO: 5 has been substituted with N. That is, only the HCDR2 of these sequences differs from the mouse parent antibody IGF11-16 HCDR2 (SEQ ID NO: 86). See paragraph [0158] and Tables 10-11 of the specification.
The VL of SEQ ID NOS: 65 and 67 have the CDRs of SEQ ID NOS: 88, 89, and 90. That is, none of the CDRs differ from the mouse parent antibody IGF11-16.
The VL of SEQ ID NO: 69 has the CDRS of SEQ ID NOS: 88 and 90. The LCDR2 sequence has a substitution of L for R at the fifth amino acid position (SEQ ID NO: 11 as compared to SEQ ID NO: 88).
It would have been well known in the art that an antibody requires all six CDRs.to provide antigen binding. A single CDR or the VH alone or the VL alone is insufficient. At least for example, SYWMH (instant SEQ ID NO: 1) is found in a VH for an antibody against CD20. See at least SEQ ID NO: 14 in Table 2 of Dunn et al. (U.S. Patent Application Publication 2007/0136826). At least for example, KASNLHT (instant SEQ ID NO: 11) is found in a VL for an antibody against CD277. See at least SEQ ID NO: 11 in claim 5 of Olive et al. (U.S. Patent Application Publication 2015/0353643). Iwashashi et al. discloses that the effect of CDR replacement or a single amino acid change on the antigen binding site structure can only be known by actual structural analysis. The specification does not disclose those CDR amino acid substitutions that will result in IGF-1 receptor binding and the functional characteristics of the claims. Again, antigen binding depends upon all six CDRs. Substituting amino acids in these CDRs would result in unpredictability with respect to the binding properties of the resulting protein. Making multiple substitutions in multiple CDRs would result in unpredictability with respect to the binding properties of the resulting protein. The claims include a great deal of variability with respect to unlimited substitutions in all CDRs simultaneously (see claim 1) and more limited substitutions in all CDRs simultaneously (see claims 3-5 and 7).
The specification provides limited antibodies having the structures and properties recited in the claims and the structural variability of the claimed genus is large. No reasonable structure-function correlation has been established that is commensurate in scope with the claims, particularly with respect to the functional properties of claims 6 and 11-24, some of which are highly complex functions. The specification does not describe representative examples to support the full scope of the claims. The specification does not disclose those amino acid(s) in the CDRs that can be changed (and what they can be changed to) while retaining the required functions. Note that in most cases the claims do not require any particular framework sequences or constant domain sequences. The particular antibodies exemplified with respect to the various recited functions have particular framework sequences and particular mutations to these sequences as compared to the mouse parent IGF11-16 antibody sequences. Antibodies that activate the IGF-1 receptor are shown in Table 12. See claim 12. Table 16 shows the binding affinity for only two specific antibodies as compared to the parent antibody. Examples 20-21 show limited inhibitory effects of the mouse parent IGF11-16 antibodies. No inhibitory effects are shown for antibodies within the scope of the claims, particularly variants commensurate in scope with the claims.
Claims 12-24 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for the specifically exemplified antibodies in the examples, does not reasonably provide enablement for all antibodies encompassed by the claims. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
The genus of antibodies claimed lacks written description for the reasons set forth above. Because the structures of the antibodies having the claimed properties are not adequately described, the scope of the claims is not enabled. It would constitute undue experimentation to determine which antibodies encompassed by claim 1 but not exemplified or tested in the specification examples would have the properties recited in claims 12-24.
In In re Wands (8 USPQ2d 1400 (CAFC 1988)) the CAFC considered the issue of enablement in molecular biology. The CAFC summarized eight factors to be considered in a determination of "undue experimentation." These factors include: (a) the quantity of experimentation necessary; (b) the amount of direction or guidance presented; (c) the presence or absence of working examples; (d) the nature of the invention; (e) the state of the prior art; (f) the relative skill of those in the art; (g) the predictability of the art; and (h) the breadth of the claims.
In the instant application the breadth of the claims is large with respect to the antibodies encompassed and multiple functional activities are required by the antibodies. Note that claims encompass any normal mammal (claim 15), any hypophysectomized model animal (claim 16), any vertebrate animal (claim 17-18), any cancer-bearing model animal (claims 23-24), any cancer cell (claim 21-22), and any cell proliferative disorder (claim 22). There is no guidance or direction with respect to the structure of those antibodies having the recited functions. A large amount of experimentation would be required to determine those antibodies within the scope of the claims that have the recited functions. The examples in the specification are not commensurate in scope to the claims and their results could not be extrapolated to other antibodies within the scope of the claims.
It would constitute undue experimentation to determine those antibodies within the scope of the claims having the recited properties.
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 1-24 and 29 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.
The claims are directed in part to a “derivative” of an antibody. The specification discloses that “derivatives” include nanobodies, VHH, or antibodies consisting only of a heavy chain or of a light chain. This is confusing as the claims require both a heavy and a light chain which would preclude these derivatives. The specification does not provide a limiting definition for an antibody “derivative” and the metes and bounds of the claims cannot be determined. It is noted that the specification does not disclose any single domain antibodies.
Claim 4 depends upon claim 1. Claim 4 is confusing in reciting having a homology of 80, 82, 75, 81, 85, 77% or more to the CDRs of SEQ ID NOS: 1, 3, 7, 9, 11, and 13, respectively. At least for example, this permits 100% homology to each of these sequences which is in conflict with the requirement that at least one of the CDRs contains a substitution of at least one amino acid residue in claim 1. The claim is confusing and does not appear to be properly dependent. Note that the CDRs of parent antibody IGF11-16 are disclosed as corresponding to SEQ ID NOS: 85, 86, 87, 88, 89, and 90. See at least first full paragraph on page 19 of the specification. SEQ ID NOS: 85, 86, 87, 88, 89, and 90 are identical to SEQ ID NOS: 1, 3, 7, 9, 11, and 13, respectively.
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.
Claim 29 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. 1. The pharmaceutical composition of claim 29 requires nothing more than the product of instant claim 1. 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.
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 1, 3-6, 8, 12-13, 17, 19, 22, and 29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 and 28-44, of U.S. Patent No.11,629,194. Although the claims at issue are not identical, they are not patentably distinct from each other.
Issued claim 1 is directed an anti-IGF-1 receptor antibody that can induce growth of vertebrate-derived cells (i.e. the activation of instant claim 12). The antibody has the CDRs of SEQ ID NO: 3, 4, 5, 6, 7, and 8 (identical to instant SEQ ID NO: 1, 3, 7, 9, 11, and 13, respectively) where one amino acid substitution can be made in CDR-H1 and CDRL-2 as well as one or two amino acid substitutions can be made in CDR-H2, CDR-H3, CDR-L1, and CDR-L3 for the VH CDRs of SEQ ID NOS: 3, 4, and 6 and for the VL CDRs of SEQ ID NOS: 6, 8, and 8. Humanization of the antibodies in issued claim 1 is implicit as no particular framework regions are required and would include human immunoglobulin framework regions. This meets the requirements of instant claims 1 and 3-5 (where one amino acid is substituted in each CDR as permitted by issued claim 1). Issued claims 14-15 are directed to the binding of instant claim 6. SEQ ID NO: 32 corresponds to amino acids 308-319 of instant SEQ ID NO: 71. Issued claim 12 discloses the limitations of instant claim 18. Issued claim 17 recites the limitations of instant claim 17. Issued claim 18 discloses the inhibition of instant claims 19 and 22. Issued claim 23 discloses constant regions from humans (i.e. any class of human immunoglobulin). See instant claim 8. Issued claim 31 is directed to the pharmaceutical compositions of instant claim 29. Issued claim 39 is considered to meet the limitations of instant claim 13.
The VH amino acid sequences of instant SEQ ID NOS: 43, 47, 49, 53, 55, and 59 are free of the prior art. SEQ ID NOS: 47, 53, and 59 contain the CDRs of instant SEQ ID NOS: 1, 5, and 7. SEQ ID NOS: 43, 49, and 55 have the CDR of SEQ ID NO: 5 where the sixth amino acid is Asn (N) not Ser (S). SEQ ID NOS: 43, 49, and 55 have the CDRs of SEQ ID NOS: 1 and 7.
The VL amino acid sequences of instant SEQ ID NOS: 65, 67, and 69 are free of the prior art. SEQ ID NOS: 65 and 67 have the CDRs of SEQ ID NOS: 9, 11, and 13. SEQ ID NO: 69 has the CDRs of SEQ ID NOS: 9 and 13. The LCDR2 sequence of SEQ ID NO: 69 has a substitution of L for R at the fifth amino acid position of SEQ ID NO: 11.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MARIANNE P ALLEN whose telephone number is (571)272-0712. The examiner can normally be reached 7:00-3:30 EST Monday-Friday.
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/Marianne P Allen/Primary Examiner, Art Unit 1647
mpa