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 .
Applicant's arguments filed 2/6/2026 have been fully considered but they are not persuasive.
Claims 1-11, 15, and 25-50 have been cancelled.
Sato et al. (U.S. Patent No. 10,870,699); Sato et al. (U.S. Patent No. 11,787,860); Sato et al. (U.S. Patent Application Publication 2017/0369572); and Sato et al. (U.S. Patent Application Publication 2021/0054070) have been disqualified as prior art under 35 USC 102(a)(2) in view of applicant’s conspicuous statement of common ownership. Applicant has invoked an exception under 35 USC 102(b)(2)(C).
It is again noted that applicant did not invoke any exceptions under 35 USC 102(b)(1) or 35 USC 102(b)(2) to remove Sato et al. (WO 2016/109415, of record) as prior art under 35 USC 102(a)(1) or 35 USC 102(a)(2). Sato et al. (WO 2016/109415, of record) remains prior art under 35 USC 102(a)(1) and (102(a)(2).
Claim Rejections - 35 USC § 103
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 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 12-14, 16-19, 22-24, and 51-57 are rejected under 35 U.S.C. 103 as being obvious over Grosveld et al (U.S. Patent Application Publication 2017/0081407, of record) in view of Salazar-Fontana (2017, of record), Bolen et al. (U.S. Patent Application Publication 2017/002020), and Sato et al. (WO 2016/109415; published 7 July 2016; filed 28 December 2015; inventorship Sato, Stafford, and Yang; applicant Celgene Corporation; of record).
The applied Sato et al. reference has a common applicant (Celgene Corporation) with the instant application. It has no inventors in common 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). WO 2016/109415 is also prior art under 35 U.S.C. 102(a)(1) but was published less than a year prior to the effective filing date of the instant application. Applicant has not invoked any exceptions with respect to this document. The reference has not been removed as valid prior art.
Grosveld et al. teaches a method of treating or preventing cancer in a subject in need thereof, comprising administering to the subject an anti-CD47 antibody. See at least abstract and paragraph [0007]. Grosveld et al. further teaches administering the anti-CD47 antibody with an opsonizing antibody molecule (see at least paragraphs [0047, 0050]) that is an anti-CD20 antibody molecule such as rituximab (see at least paragraph [0051]). Rituximab was administered at 5 mg/kg. See at least paragraphs [0071, 0221, and 0224]. This is an effective dose of rituximab as disclosed in the instant specification at paragraph [0053]. Administration of anti-CD47 antibodies and rituximab had synergistic improvement of tumor growth inhibition. See at least paragraph [0224]. Claims 14, 23-24, and 26-28 of Grosveld et al. disclose this method with respect to specific anti-CD47 antibodies. However, Grosveld et al. specifically discloses that anti-CD47 antibodies known in the art such as AB6.12, AB6.12-IgG4P, and AB6.12_IgG4PE could be used. See at least paragraph [0149]. The complete amino acid sequences for these antibodies are not disclosed in Grosveld et al. Note that SEQ ID NO: 28 (107 amino acids) for the VL disclosed in paragraph [0149] corresponds to amino acids 2-108 of instant SEQ ID NO: 88 (215 amino acids) recited in instant claims 51 and 52. The VH of SEQ ID NO: 27 is 118 amino acids.
Regarding instant claims 17-18, Grosveld et al. further teaches that methods of the invention may include one or more additional therapies, and recites wherein these therapies may include radiation therapy or chemotherapy (see at least paragraph [0193]).
Regarding instant claims 19 and 56, Grosveld et al. further discloses wherein the effective amount of anti-CD47 antibody is in the 0.1 mg/kg to 100 mg/kg range, and more particularly 1 mg/kg to 10 mg/kg. The reference further teaches that human dosage can be optimized in a Phase I escalation study designed to run from 0.5 mg/kg to 20 mg/kg. See at least paragraph [0186].
Regarding instant claims 22-24, Grosveld et al. discloses an example in which anti-CD47 is administered in a mouse subject in combination with rituximab without proteosome inhibitor, bortezomib, or methotrexate (see at least Example 3 and paragraphs [0220-0221]) resulting in profound tumor growth inhibition both as a single agent and in combination (see at least paragraph [0225]).
Regarding instant claims 14, 16, and 56, Grosveld et al. further teaches that for therapeutic use, an antibody preferably is combined with a pharmaceutically acceptable carrier, meaning buffers, carrier, and excipients suitable for use in human beings and animals (see at least paragraph [0167-0168, 0175-0176, and 0181]). Subjects and patients may preferably include mammals, and more preferably humans (see at least paragraph [0185]).
Grosveld et al. does not disclose the anti-CD47 antibodies recited in instant claims 51 and 52.
Salazar-Fontana et al. discloses that depleting B cells can be used to control unwanted antibody responses against therapeutic proteins (i.e. anti-drug antibody (ADA) responses). See page 380, right column, last full paragraph.
Bolen et al. discloses that rituximab would have been known to be a B-cell depleting agent. See at least paragraph [0433].
Sato et al. (WO 2016/109405) discloses anti-CD47 antibodies within the instant claims. At least for example, Table 1 on page 18 discloses a 13m VH of SEQ ID NO: 21 that corresponds to instant SEQ ID NO: 90 and a 5m VH of SEQ ID NO: 22 that corresponds to instant SEQ ID NO: 91. The anti-CD47 heavy chains sequences of SEQ ID NOS: 5-11 correspond to instant SEQ ID NOS: 81-87, respectively. See pages 19-21. Paragraph [0090] on page 21 discloses a VL of SEQ ID NO: 13 that corresponds to instant SEQ ID NO: 88. This VL can omit the M at the N-terminus. Sato et al. discloses anti-CD47 antibodies in the IgG1, IgG4P, or IgG4PE format. See at least Table 2 starting at page 38; page 65; and paragraph [0051]. The antibodies can be used to treat cancer. Sato et al. discloses administering the anti-CD47 antibodies in combination with other therapies including anti-cancer agents. See at least paragraphs [0024-0028; 00199-00201; and 00212].
It would have been obvious to administer rituximab and anti-CD47 antibodies as in the method of treating cancer of Grosveld et al. where the anti-CD47 antibodies are those disclosed by Sato et al. One would have been motivated to do so as the antibodies of Sato et al. would have been suitable anti-CD47 antibodies. In addition, Sato et al. discloses administering the anti-CD47 antibodies in combination with other therapies. Rituximab would have been known as a useful therapy in treating cancer as evidenced by Grosveld et al. Administration of rituximab would have been known to deplete B cells as taught by Bolen et al. and this depletion would have reduced immunogenicity within the meaning of the claims as taught by Salazar-Fontana et al. The amounts of rituximab administered by Grosveld et al. are within the amounts disclosed as being effective in the instant specification. “Reducing immunogenicity” in the claims is considered to include depletion of B cells in the absence of a more specific definition or limitation in the claims. The property or characteristic of rituximab to reduce immunogenicity when administered cannot be separated from the compound.
Applicant’s arguments that the teachings of Grosveld are limited to the combination of rituximab and anti-CD47 antibody 2.3D11 or anti-CD47 antibody B6H12 to treat cancer are not persuasive. The disclosure of Grosveld is not limited to only these anti-CD47 antibodies but would fairly suggest to one of ordinary skill at the time of the effective filing date the use of other anti-CD47 antibodies with rituximab. Grosveld et al. specifically discloses that other anti-CD47 antibodies known in the art such as AB6.12, AB6.12-IgG4P, and AB6.12_IgG4PE could be used. See at least paragraph [0149]. The complete amino acid sequences for these antibodies are not disclosed in Grosveld et al. Note that this paragraph discloses SEQ ID NO: 28 (107 amino acids) for the VL which corresponds to amino acids 2-108 of instant SEQ ID NO: 88 (215 amino acids) recited in claims 51 and 52. The VH of SEQ ID NO: 27 is 118 amino acids.
Grosveld et al. specifically teaches administering any anti-CD47 antibody with an opsonizing antibody molecule (see at least paragraphs [0047, 0050] of Grosveld et al.) that is an anti-CD20 antibody molecule (see at least paragraph [0051] of Grosveld et al.) such as rituximab (see at least paragraph [0051] of Grosveld et al.) in a method of treating or preventing cancer. This would have fairly suggested to one of ordinary skill in the art that any anti-CD47 antibody could have been used. Advantages of including opsonizing antibodies such as rituximab are disclosed. See paragraphs [0050-0051] of Grosveld et al. Again, Grosveld et al. specifically discloses that anti-CD47 antibodies known in the art such as AB6.12, AB6.12-IgG4P, and AB6.12_IgG4PE could be used. See at least paragraph [0149]. The complete amino acid sequences for these antibodies are not disclosed in Grosveld et al. Note that SEQ ID NO: 28 (107 amino acids) for the VL corresponds to amino acids 2-108 of instant SEQ ID NO: 88 (215 amino acids) recited in claims 51 and 52. While the full sequence of instant SEQ ID NO: 88 is not disclosed in Grosveld et al., it is fully disclosed in Sato et al. as SEQ ID NO: 13. The VH/VL sequences for AB6.12 are SEQ ID NOS: 11 and 12 in Sato et al. The AB6.12 IgG1 heavy chain sequences of SEQ ID NOS: 5-7, the AB6.12 IgG4P heavy chain sequences SEQ ID NOS: 8-9, and the AB61.12 IgG4PE heavy chain sequences of SEQ ID NOS: 10-11 are disclosed in Sato et al. As Grosveld et al. (filed 21 September 2016) has a filing date later than that of Sato et al. (filed 28 December 2015), one of ordinary skill in the art would have known the CDC related properties for these antibodies as disclosed by Sato et al. at the time of the filing date of Grosveld et al.
Sato et al. discloses anti-CD47 antibodies within the scope of the claims that would have been known to be useful to treat cancer. Again, Table 1 of Sato et al. on page 18 discloses a 13m VH of SEQ ID NO: 21 that corresponds to instant SEQ ID NO: 90 and a 5m VH of SEQ ID NO: 22 that corresponds to instant SEQ ID NO: 91. The anti-CD47 heavy chains sequences of SEQ ID NOS: 5-11 correspond to instant SEQ ID NOS: 81-87, respectively. See pages 19-21. Paragraph [0090] on page 21 discloses a VL of SEQ ID NO: 13 that corresponds to instant SEQ ID NO: 88.
In addition, Salazar-Fontana et al. and Bolen et al. also provide motivation to administer rituximab.
Applicant is arguing the references separately and not for what the combination of references would have fairly suggested to one of ordinary skill in the art at the time of the effective filing date.
The combination of the prior art provides ample motivation to combine the teachings of the prior art to arrive at the claimed method. There would have been an expectation of success that administering the suggested anti-CD47 antibody and rituximab would have treated cancer as recited by instant claim 51 and reduce immunogenicity as recited by instant claim 52.
Claims 20, 51-52, and 57 are rejected under 35 U.S.C. 103 as being obvious over Grosveld et al (U.S. Patent Application Publication 2017/0081407, of record) in view of Salazar-Fontana (2017, of record), Bolen et al. (U.S. Patent Application Publication 2017/0002060), and Sato et al. (WO 2016/109415, of record) as applied to claims 12-14, 16-19, 22-24, and 51-57, above, and further in view of Onrust et al. (of record).
Grosveld et al (U.S. Patent Application Publication 2017/0081407, of record); Salazar-Fontana (2017, of record); Bolen et al. (U.S. Patent Application Publication 2017/0002060), Sato et al. (U.S. Patent No. 10,870,699); and Sato et al. (WO 2016/109415, of record)) are applied as above.
The references do not teach the dosages in instant claims 20 and 57 (i.e. a dose of 300, 325, 350, 375, 400, 425, 450, or 500 mg/m2).
Onrust discloses that 375 mg/m2 is the recommended dosage of rituximab (p. 79, table “Features and properties of rituximab”) and further discloses that chemotherapy plus rituximab 375 mg/m2 produced significantly more lymphoma cell-free progenitor cell harvests than chemotherapy alone.
It would have been obvious to one of ordinary skill in the art before the effective filing date to have administered rituximab at 375 mg/m2 in the method suggested by the combination of Grosveld et al (U.S. Patent Application Publication 2017/0081407, of record); Salazar-Fontana (2017, of record); Bolen et al. (U.S. Patent Application Publication 2017/0002060), and Sato et al. as set forth above in view of Onrust’s teaching that this is the recommended dosage and that this dosage was effective in producing lymphoma cell-free progenitor cell harvests when combined with chemotherapy. This dosage would have been expected to reduce immunogenicity within the meaning of the claims.
Applicant’s arguments are unpersuasive. Arguments with respect to Grosveld et al. and Sato are addressed above.
Claims 21, 51-52, and 58 are rejected under 35 U.S.C. 103 as being obvious over Grosveld et al (U.S. Patent Application Publication 2017/0081407, of record) in view of Salazar-Fontana (2017, of record), Bolen et al. (U.S. Patent Application Publication 2017/0002060), and Sato et al. (WO 2016/109415, of record) as applied to claims 12-14, 16-19, 22-24, and 51-57 above, and further in view of Van Den Berg et al. (U.S. Patent Application Publication 2017/0275364, of record).
Grosveld et al (U.S. Patent Application Publication 2017/0081407, of record); Salazar-Fontana (2017, of record); Bolen et al. (U.S. Patent Application Publication 2017/0002060), and Sato et al. (WO 2016/109415, of record) are applied as above.
The references do not teach administering the rituximab prior to the anti-CD47 antibodies.
Van Den Berg et al. disclosing treating cancer where rituximab can be administered prior to an anti-CD47 antibody. See at least claim 33.
It would have been obvious to one of ordinary skill in the art before the effective filing date to have administered rituximab prior to the anti-CD47 antibody as taught by Van Den Berg et al. in the method suggested by the combination of Grosveld et al (U.S. Patent Application Publication 2017/0081407, of record); Salazar-Fontana (2017, of record); Bolen et al. (U.S. Patent Application Publication 2017/0002060), and Sato et al. The administration of rituximab prior to the administration of the anti-CD47 antibody would have been expected to reduce immunogenicity within the meaning of the claims.
Applicant’s arguments are unpersuasive. Arguments with respect to Grosveld et al. and Sato are addressed above.
Conclusion
THIS ACTION IS MADE FINAL. 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.
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/Marianne P Allen/Primary Examiner, Art Unit 1647
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