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
Claims 1-24 are pending in the instant application and being examined on the merit.
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.
Claims 1-15 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US 20180022817 (Berne P-F et al. IDS reference).
Regarding instant claims 1-15, Berne taught an anti-CEACAM5 immunoconjugate huMAb2-3-SPDB-DM4, which comprised an anti-CEACAM5 antibody comprising a heavy chain of SEQ ID NO: 87 and a light chain of SEQ ID NO:88 (page 27, [0504]-[505]), a SPDB linker of N-succinimidyl pyridyldithiobutyrate, and a maytansinoid DM4 (page 17, [0284]), wherein the drug to antibody ratio is about 4 (page 39, [0656] – [0662] and Fig. 14) and further taught an effective method of treating subjects with human colorectal cancer comprising administering a pharmaceutical composition of huMAb2-3-SPDB-DM4 and a pharmaceutically acceptable excipient (page 2, [0020]; page 40, [0678]-[0680] and Table 20; and Fig. 5). Thus, the anti-CEACAM5 immunoconjugate of Berne can be used for treating cancer in combination with FOLFOX. The immunoconjugate huMAb2-3-SPDB-DM4 (instant claims 12) has: 1) an identical antibody sequence to the heavy chain instant SEQ ID NO:8 and light chain instant SEQ ID NO:9, and further is comprised of a VH of instant SEQ ID NO:6 and a VL of instant SEQ ID NO:7 and CDR-H1-3 of SEQ ID NO:1-3 and CDR-L1-3 of SEQ ID NO:4, NTR, and 5 (instant claims 2-4) – see alignment below; 2) a SPDB linker (instant claims 10-11); 3) a conjugated maytansinoid DM4 (instant claims 5-9); and a DAR of about 4 (instant claim 13) and further meets the claim limitations of instant claims 1 and 14-15.
Alignment of heavy chain Berne SEQ ID NO:87 and instant SEQ ID NO:8
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544
580
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Alignment of light chain Berne SEQ ID NO:89 and instant SEQ ID NO:9
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293
586
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Claim Rejections – 35 USC § 103
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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-18 and 20-24 are rejected under 35 U.S.C. 103 as being unpatentable over US 20180022817 (Berne P-F et al. IDS reference) as applied to claims 1-15 above, and further in view of Jeon H-J et al. (J Korean Soc Coloproctol. 2011 Jun 30;27(3):140–146) and NCT03324113 Clinical Trial (https://clinicaltrials.gov/study/NCT03324113?tab=history&a=10#version-content-panel Date 3/2019).
Berne is described above and taught the limitations of claims 1-15 for the reasons set forth above.
Regarding instant claims 16-18 and 20-24, Berne further taught an effective method of treating subjects with human colorectal cancer comprising administering a pharmaceutical composition of huMAb2-3-SPDB-DM4 and a pharmaceutically acceptable excipient, which caused a dose dependent decrease from 2.5 to 10 mg/kg of tumors in subjects (page 2, [0020]; page 40, [0678]-[0680] and Table 20; and Fig. 5). Thus, huMAb2-3-SPDB-DM4 is a results effective variable for colorectal cancer treatment.
Regarding instant claims 16-18, 20, and 22, Berne taught the immunoconjugate may be used in combination with any suitable growth-inhibitory agent (page 23, [0378]) and in combination with any other therapeutical strategy for treating malignant tumor (e.g. adjuvant therapy), and/or for reducing the growth of the metastatic tumor (page 24, [0389]).
Regarding instant claims 21 and 23, Berne taught the immunoconjugate in a kit (page 26, [0437]).
While Berne taught the immunoconjugate may be used in combination with other agents for cancer therapy, Berne is silent to: 1) a treatment method comprising administering and immunoconjugate comprising an anti-CEACAM5-antibody in combination with FOLFOX specifically; or 2) a pharmaceutical composition or kit of an anti-CEACAM5-antibody with FOLFOX specifically, but this is obvious in view of Jeon and NCT03324113.
Regarding instant claims 1-24, Jeon taught chemotherapy using the FOLFOX regimen, oxaliplatin in combination with 5-fluorouracil and leucovorin, is effective and tolerable in patients with colon cancer (abstract).
Regarding instant claims 1-24, NCT03324113 taught combination treatment of the CEACAM5 antibody drug conjugate SAR408701, which is also known as huMAb2-3-SPDB-DM4, and the chemotherapeutic agent TAS-102 comprising trifluridine and tipiracil (page 11, SAR408701 and TAS-102 combination row).
Regarding instant claims 16-18 and 20-24, it would have been obvious for a person having ordinary skill in the art to take the effective method of treating subjects with human colorectal cancer of Berne comprising administering a pharmaceutical composition of huMAb2-3-SPDB-DM4 and a pharmaceutically acceptable excipient to subjects in need thereof – and to further: 1) prepare a pharmaceutical composition with the huMAb2-3-SPDB-DM4 immunoconjugate and include FOLFOX as a separate pharmaceutical composition for the treatment in view of Berne and Jeon; 2) administer the pharmaceutical composition comprising the immunoconjugate and FOLFOX in view of Berne and Jeon; and 3) prepare a kit of the pharmaceutical composition comprising the immunoconjugate and FOLFOX in view of Berne.
This is obvious because: 1-2a) Berne taught the immunoconjugate may be used in combination with any suitable growth-inhibitory agent and in combination with any other therapeutical strategy for treating malignant tumor (e.g. adjuvant therapy), and/or for reducing the growth of the metastatic tumor; 1-2b) Jeon taught chemotherapy using the FOLFOX regimen, oxaliplatin in combination with 5-fluorouracil and leucovorin, is effective and tolerable in patients with colon cancer; 1-2c) NCT03324113 taught combination treatment of subjects with colon cancer wherein SAR408701, which is also known as huMAb2-3-SPDB-DM4, and the cancer chemotherapeutic TAS-102. Thus it would be obvious to exchange one colon cancer chemotherapeutic for another effective one for combination therapy with huMAb2-3-SPDB-DM4; and 3) Berne taught the immunoconjugate in a kit and a single kit would allow all components of treatment to be packaged together for easier ordering and tracking.
There is a reasonable expectation of success because: 1-2a) huMAb2-3-SPDB-DM4 is effective for treating subjects with colorectal cancer; 1-2b) FOLFOX is effective and tolerable in patients with colon cancer. Treatment of two known effective colon cancer treatment agents would be expected to be effective when administered in combination; and 3) a single kit would allow all components of treatment to be packaged together for easier ordering and tracking.
This would produce an effective method of treating subjects with human colorectal cancer comprising preparing then administering a pharmaceutical composition comprising:
huMAb2-3-SPDB-DM4 and a pharmaceutically acceptable excipient; and
FOLFOX and a pharmaceutically acceptable excipient,
to subjects in need thereof (instant claims 16-18, 20, 22, and 24), wherein the pharmaceutical composition is prepared as huMAb2-3-SPDB-DM4 and a pharmaceutically acceptable excipient and FOLFOX as separate pharmaceutical compositions for the treatment, and wherein the pharmaceutical composition comprising huMAb2-3-SPDB-DM4 and FOLFOX are in a kit prior to administration (instant claims 21 and 23).
Claims 1-24 are rejected under 35 U.S.C. 103 as being unpatentable over US 20180022817 (Berne P-F et al. IDS reference), Jeon H-J et al. (J Korean Soc Coloproctol. 2011 Jun 30;27(3):140–146) and NCT03324113 Clinical Trial (https://clinicaltrials.gov/study/NCT03324113?tab=history&a=10#version-content-panel Date 3/2019) as applied to claims 1-18 and 20-24 above, and further in view of Dotan E et al. (J Clin Oncol. 2017 Aug 17;35(29):3338–3346) and Center for Drug Evaluation and Research (CDER) et al. (http://www.fda.gov/cder/guidance/index.htm).
Berne, Jeon, and NCT03324113 are described above.
Regarding instant claim 19, Berne further taught an effective method of treating subjects with human colorectal cancer comprising administering a pharmaceutical composition of huMAb2-3-SPDB-DM4 and a pharmaceutically acceptable excipient, which caused a dose dependent decrease from 2.5 to 10 mg/kg of tumors in subjects (page 2, [0020]; page 40, [0678]-[0680] and Table 20; and Fig. 5). Thus, huMAb2-3-SPDB-DM4 is a results effective variable for colorectal cancer treatment.
Regarding instant claim 19, Berne further taught a person having ordinary skill in the art can determine the appropriate dose, wherein:
A) Some variation in dosage will necessarily occur depending on the condition of the subject being treated. The person responsible for administration will, in any event, determine the appropriate dose for the individual subject (page 23, [368]);
B) The antibody or immunoconjugate of the invention may be formulated within a therapeutic mixture to comprise about 0.01 to 100 milligrams, per dose or so (page 23, [0369]); and
C) a “therapeutically effective amount” of the polypeptide of the invention is meant a sufficient amount of the polypeptide to treat said cancer disease, at a reasonable benefit/risk ratio applicable to any medical treatment. It will be understood, however, that the total daily usage of the polypeptides and compositions of the present invention will be decided by the attending physician within the scope of sound medical judgment. The specific therapeutically effective dose level for any particular patient will depend upon a variety of factors including the disorder being treated and the severity of the disorder; activity of the specific polypeptide employed; the specific composition employed, the age, body weight, general health, sex and diet of the patient; the time of administration, route of administration, and rate of excretion of the specific polypeptide employed; the duration of the treatment; drugs used in combination or coincidental with the specific polypeptide employed; and like factors well known in the medical arts. For example, it is well known within the skill of the art to start doses of the compound at levels lower than those required to achieve the desired therapeutic effect and to gradually increase the dosage until the desired effect is achieved (page 24, [0386]).
Regarding instant claim 19, Jeon taught the FOLFOX regimen consisted of administering 200 mg/m2 leucovorin (LV), 1000 mg/m2 5-fluorouracil (5-FU), and 85 mg/m2 oxaliplatin to colon cancer patients on day 1 (page 141, left column, last paragraph). Regarding instant claim 19 Jeon taught 82% of patients were able to receive at least 10 of 12 cycles of the FOLFOX regimen, with a median of 12 cycles (page 142, left column, second paragraph and Table 3).
Berne did not teach 1) the immunoconjugate comprising an anti-CEACAM5-antibody, and FOLOFOX are administered in 8 to 16 cycles wherein one cycle comprises: administering the immunoconjugate at a dosage of from 60 to 210 mg/m2, at least once in a cycle; and administering FOLFOX, wherein administering folinic acid at a dose of from 100 to 300 mg/m2 at least once in the cycle; administering 5-fluoro-uracil at a dose of from 1000 to 2000 mg/m2, at least once in the cycle, and administering oxaliplatin at a dose of from 50 to 200 mg/m2, at least once in the cycle, but this is obvious in view of Jeon, Dotan and CDER.
Regarding instant claim 19, Dotan taught administration of 6 mg/kg of an anti-CEACAM5-SN38 immunoconjugate twice per week in 3 week cycles to a human subject with colorectal cancer was effective (abstract and Table 2 and Fig. 3). Dotan taught subjects were dosed with a range of one to 43 cycles (page 3339, right column, last paragraph) and a 6 mg/kg dose was effective in a subject with colorectal cancer wherein a partial response with a 63% reduction of cancer was observed at 13 months (page 3342, Fig. 1 legend)
Regarding instant claim 19, CDER taught conversion of mouse dose to human dose requires multiplication by 0.081 (page 19, Table 3). Thus, regarding huMAb2-3-SPDB-DM4, a mouse dose of 10 mg/kg for humans = (10 mg/kg) * (conversion factor of 0.081) = 0.81 mg/kg human dose
CDER taught conversion of human dose mg/kg to mg/m2 requires multiplication of a km factor constant of 37 (page 19, Table 3). Thus, regarding 0.81 mg/kg huMAb2-3-SPDB-DM4, a human dose of 0.81 mg/kg to mg/m2 = (0.81 mg/kg) * (km factor of 37) = 30 mg/m2 human dose
Further, regarding an anti-CEACAM5-SN38 immunoconjugate, CDER taught conversion of human dose mg/kg to mg/m2 requires multiplication of a km factor constant of 37 (page 19, Table 3).
Thus, for a dose of 6 mg/kg an anti-CEACAM5-SN38 immunoconjugate, (6 mg/kg) * (km factor of 37) = 222 mg/m2
Regarding instant claim 19, it would have been obvious for a person having ordinary skill in the art to take the method of Berne, Jeon, and NCT03324113 above – and to further: 1) treat human subjects with FOLFOX wherein the FOLFOX regimen consisted of administering 200 mg/m2 leucovorin (LV), 1000 mg/m2 5-fluorouracil (5-FU), and 85 mg/m2 oxaliplatin to colon cancer patients at least once in a cycle for 10 to 12 cycles as taught by Jeon; 2) treat human subjects with an anti-CEACAM5 immunoconjugate dose of between 30 mg/m2 and 222 mg/m2 every two weeks for between 1 and 43 cycles in view of Berne, Dotan, and CDER; and 3) administer treatment for 10-12 cycles because 10-12 cycles of FOLFOX is known to be effective and 43 cycles of an anti-CEACAM5 immunoconjugate is known to be tolerable.
This is obvious because:
1) Jeon taught FOLFOX was effective in colon cancer patients and that the FOLFOX4 regimen consisted of administering 200 mg/m2 leucovorin (LV), 1000 mg/m2 5-fluorouracil (5-FU), and 85 mg/m2 oxaliplatin to colon cancer patients at least once per cycle and 82% of patients were able to receive at least 10 of 12 cycles of the FOLFOX regimen, with a median of 12 cycles;
2a) Dotan taught administration of 6 mg/kg of an anti-CEACAM5-SN38 immunoconjugate twice per week in 3 week cycles to a human subject with colorectal cancer was effective with a range of one to 43 cycles. A 6 mg/kg dose of the anti-CEACAM5 immunoconjugate taught by Dotan requires a conversion factor of 37 which yields a dose of 222 mg/m2 with a range of 1-43 cycles;
2b) Berne taught an effective method of treating subjects with human colorectal cancer comprising administering a pharmaceutical composition of huMAb2-3-SPDB-DM4 and a pharmaceutically acceptable excipient, which caused a dose dependent decrease from 2.5 to 10 mg/kg of tumors in subjects, wherein treatment of colorectal cancer with huMAb2-3-SPDB-DM4 was a results effective variable. Conversion of 10 mg/kg huMAb2-3-SPDB-DM4 in mice to humans and yields a human dosage in mg/m2 of 30 mg/m2.
Thus, an anti-CEACAM5 immunoconjugate dose of between 30 mg/m2 and 222 mg/m2 every two weeks for between 1 and 43 cycles would be tolerable and within the range of 10-12 cycles which is effective for FOLFOX. Thus, 10-12 cycles of the combined composition would be obvious and within the skill of a person having ordinary skill in the art, which overlaps with a dose of an anti-CEACAM5-antibody, and FOLFOX administered in 8 to 16 cycles wherein one cycle comprises: administering the immunoconjugate at a dosage of from 60 to 210 mg/m2, at least once in a cycle; and administering FOLFOX, wherein the FOLFOX regimen consists of administering 200 mg/m2 leucovorin (LV), 1000 mg/m2 5-fluorouracil (5-FU), and 85 mg/m2 at least once per cycle.
There is a reasonable expectation of success because:
1) Jeon taught FOLFOX was effective in colon cancer patients and that the FOLFOX regimen consisted of administering 200 mg/m2 leucovorin (LV), 1000 mg/m2 5-fluorouracil (5-FU), and 85 mg/m2 oxaliplatin to colon cancer patients at least once per cycle and 82% of patients were able to receive at least 10 of 12 cycles of the FOLFOX regimen, with a median of 12 cycles;
2a) Dotan taught administration of 6 mg/kg of an anti-CEACAM5-SN38 immunoconjugate twice per week in 3 week cycles to a human subject with colorectal cancer was effective with a range of one to 43 cycles. A 6 mg/kg dose of the anti-CEACAM5 immunoconjugate taught by Dotan requires a conversion factor of 37 which yields a dose of 222 mg/m2 with a range of 1-43 cycles. Thus, other anti-CEACAM5 immunoconjugates would be expected to target CEACAM5 effectively in human tumors effectively in this dose and cycle range;
2b) Berne taught an effective method of treating subjects with human colorectal cancer comprising administering a pharmaceutical composition of huMAb2-3-SPDB-DM4 and a pharmaceutically acceptable excipient, which caused a dose dependent decrease from 2.5 to 10 mg/kg of tumors in subjects, wherein treatment of colorectal cancer with huMAb2-3-SPDB-DM4 was a results effective variable. Conversion of 10 mg/kg huMAb2-3-SPDB-DM4 in mice to humans and yields a human dosage in mg/m2 of 30 mg/m2. Berne further taught a person having ordinary skill in the art can determine the appropriate dose. Thus, an anti-CEACAM5 immunoconjugate dose of between 30 mg/m2 and 222 mg/m2 every two weeks for between 10-12 cycles in combination with FOLFOX would have a reasonable expectation of success to a person having ordinary skill in the art.
This would produce a method of treating subjects with human colorectal cancer comprising preparing then administering a pharmaceutical composition comprising at least two separate pharmaceutical compositions of:
30-222 mg/m2 huMAb2-3-SPDB-DM4 and a pharmaceutically acceptable excipient, which is between 60-210 mg/m2; and
FOLFOX comprising 200 mg/m2 leucovorin (LV), 1000 mg/m2 5-fluorouracil (5-FU), and 85 mg/m2 oxaliplatin,
wherein the subject in need thereof is administered between 10 and 12 cycles.
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 1-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 9,617,345. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding instant claims 1-15, ‘345 taught CEACAM5 antibodies in patented claims 1-7 and CEACAM5 immunoconjugates in patented claims 8-20, wherein patented claim 16 and 19 taught an anti-CEACAM5 immunoconjugate comprising a heavy chain of SEQ ID NO:87 and a light chain of SEQ ID NO:88, which is identical to instant SEQ ID NO:8 and 9, respectively, wherein the growth inhibitory agent is DM4 and the linker is SPDB (instant claim 1-12 and 14-15) and instant claim 18 taught the anti-CEACAM5 immunoconjugate is characterized by a DAR of 1 to 10 (instant claim 13).
Claims 1-11 and 13-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-40 of U.S. Patent No. 10,457,739. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding instant claims 1-15, ‘739 taught isolated nucleic acids comprising a sequence encoding CEACAM5 antibodies in patented claims 1-11, host cells comprising a nucleic acid sequence encoding CEACAM5 antibodies in patented claims 12-22, methods of producing CEACAM5 antibodies in patented claims 23-35, and methods of producing CEACAM5 immunoconjugates in patented claims 36-40. Regarding instant claims 1-11 and 14-15, patented claim 39 taught production of an anti-CEACAM5 immunoconjugate comprising a heavy chain comprising an amino acid sequence of SEQ ID NO:87 and a light chain comprising an amino acid of SEQ ID NO:88 conjugated to DM4 via a sulfo-SPDB linker, wherein the heavy and light chain are identical to instant SEQ ID NO:8 and 9, respectively (instant claim 1-11 and 14-15). Regarding instant claim 13, patented claim 38 taught a method of production of an immunoconjugate comprising a HCDR1-3 of SEQ ID NO:7-9 and LCDR1-3 of SEQ ID NO:10, NTK, and SEQ ID NO:12 and a DAR of between 1-10 (instant claim 13).
Claims 1-2, 6, and 14-15 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11,332,542. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding instant claims 1-2, 6, and 14-15, ‘542 taught methods of detecting CEACAM expressing cancer in a patient in patented claims 1-11, wherein patented claim 3 taught a fluorescent label or radiolabel conjugated to the anti-CEACAM5 immunoconjugate comprising a HCDR1-3 of SEQ ID NO:7-9 and LCDR1-3 of SEQ ID NO:10, NTK, and SEQ ID NO:12, which is identical to the HCDR1-3 and LCDR1-3 of instant SEQ ID NO:1-3 and instant SEQ ID NO:4, NTK, and SEQ ID NO:5. The method would require the claimed immunoconjugate.
Claims 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1-24 of copending Application No. 17/916,877;
claims 1-24 of copending Application No. 17/917,064;
claims 1-24 of copending Application No. 17/916,737;
claims 18-19, 23, 25-26, 31, 37-39 of copending Application No. 17/522,443, or
claims 1-2, 5, 10, 12-14, 17, 23-24, 27, 30, 32, 34, 39, 43, 47, 50, 53, and 57 of copending Application No. 18/715,558.
Although the claims at issue are not identical, they are not patentably distinct from each other because a copending claim of ‘877, ‘064, ‘737, ‘443, and ‘558 taught the huMAb2-3 SPDB DM4 immunoconjugate which is also named tusamitamab ravtansine and is identical to instant claims 1-15:
Regarding instant claims 1-15, ‘877 copending claim 12 taught an CEACAM5-antibody, which comprises a heavy chain (VH) consisting of SEQ ID NO: 8 and a light chain (VL) consisting of SEQ ID NO: 9 (huMAb2-3), and which is covalently linked to N2'-deacetyl-N-2'(4-methyl-4-mercapto-1-oxopentyl)-maytansine (DM4) via N-succinimidyl pyridyldithiobutyrate (SPDB), wherein the heavy and light chain are identical to instant SEQ ID NO:8 and 9, respectively, further the conjugate would be required to at least have a DAR of 1 (instant claim 1-15).
‘877 further taught:
an anti-CEACAM5 immunoconjugates in copending claims 1-15, a formulation of a CEACAM5 immunoconjugate and folinic acid, fluorouracil and irinotecan (FOLFIRI) in copending claim 16;
a method for treating cancer comprising administering a CEACAM5 immunoconjugate and FOLFIRI in copending claim 17, wherein the cancer is colorectal cancer in copending claim 24, wherein the immunoconjugate comprising an anti-CEACAM5-antibody, and FOLFIRI are administered in 8 to 16 cycles, wherein one cycle comprises: administering the immunoconjugate at a dosage of from 60 to 210 mg/m2, FOLFIRI dosage details in copending claim 19;
a method of making the anti-CEACAM5 immunoconjugate, wherein the immunoconjugate and FOLFIRI are formulated in the form of at least two separate pharmaceutical compositions, wherein (i) at least one pharmaceutical composition comprises the immunoconjugate, and (ii) one or more pharmaceutical compositions comprise folinic acid, 5-fluoro-uracil and irinotecan, in separate or combined formulations in copending claim 18;
a pharmaceutical composition comprising the anti-CEACAM5 immunoconjugate and folinic acid, 5-fluoro-uracil and irinotecan in copending claim 20;
a comprising (i) a pharmaceutical composition of the anti-CEACAM5 immunoconjugate and (ii) one or more pharmaceutical compositions comprising folinic acid, 5-fluoro-uracil and irinotecan, in separate or combined formulations in copending claim 21.
Regarding instant claims 1-15, ‘064 copending claim 12 taught an CEACAM5-antibody, which comprises a heavy chain (VH) consisting of SEQ ID NO: 8 and a light chain (VL) consisting of SEQ ID NO: 9 (huMAb2-3), and which is covalently linked to N2'-deacetyl-N-2'(4-methyl-4-mercapto-1-oxopentyl)-maytansine (DM4) via N-succinimidyl pyridyldithiobutyrate (SPDB), wherein the heavy and light chain are identical to instant SEQ ID NO:8 and 9, respectively, further the conjugate would be required to at least have a DAR of 1 (instant claim 1-15).
‘064 further taught:
an anti-CEACAM5 immunoconjugates in copending claims 1-15, a formulation of a CEACAM5 immunoconjugate and cetuximab in copending claim 16;
a method for treating cancer comprising administering a CEACAM5 immunoconjugate and cetuximab in copending claim 17, wherein the cancer is colorectal cancer in copending claim 24, wherein the immunoconjugate comprising an anti-CEACAM5-antibody, and cetuximab are administered in 8 to 16 cycles, wherein one cycle comprises: administering the immunoconjugate at a dosage of from 60 to 210 mg/m2, and cetuximab dosage details in copending claim 19;
a method of making the anti-CEACAM5 immunoconjugate, wherein the immunoconjugate and cetuximab are formulated in the form of at least two separate pharmaceutical compositions, wherein (i) at least one pharmaceutical composition comprises the immunoconjugate, and (ii) one or more pharmaceutical compositions comprise FOLFOX, in separate or combined formulations in copending claim 18;
a pharmaceutical composition comprising the anti-CEACAM5 immunoconjugate and cetuximab in copending claim 20;
a comprising (i) a pharmaceutical composition of the anti-CEACAM5 immunoconjugate and (ii) one or more pharmaceutical compositions comprising cetuximab, in separate or combined formulations in copending claim 21.
Regarding instant claims 1-15, ‘737 copending claim 12 taught an CEACAM5-antibody, which comprises a heavy chain (VH) consisting of SEQ ID NO: 8 and a light chain (VL) consisting of SEQ ID NO: 9 (huMAb2-3), and which is covalently linked to N2'-deacetyl-N-2'(4-methyl-4-mercapto-1-oxopentyl)-maytansine (DM4) via N-succinimidyl pyridyldithiobutyrate (SPDB), wherein the heavy and light chain are identical to instant SEQ ID NO:8 and 9, respectively, further the conjugate would be required to at least have a DAR of 1 (instant claim 1-15).
‘737 further taught:
an anti-CEACAM5 immunoconjugates in copending claims 1-15, a formulation of a CEACAM5 immunoconjugate and trifluorodine and tipiracil (TAS-102) in copending claim 16;
a method for treating cancer comprising administering a CEACAM5 immunoconjugate and TAS-102 in copending claim 17, wherein the cancer is colorectal cancer in copending claim 24, wherein the immunoconjugate comprising an anti-CEACAM5-antibody, and TAS-102 are administered in 3 to 6 cycles, wherein one cycle comprises: administering the immunoconjugate at a dosage of from 60 to 210 mg/m2, TAS-102 dosage details in copending claim 19;
a method of making the anti-CEACAM5 immunoconjugate, wherein the immunoconjugate and TAS-102 are formulated in the form of at least two separate pharmaceutical compositions, wherein (i) at least one pharmaceutical composition comprises the immunoconjugate, and (ii) one or more pharmaceutical compositions comprise TAS-102, in separate or combined formulations in copending claim 18;
a pharmaceutical composition comprising the anti-CEACAM5 immunoconjugate and TAS-102 in copending claim 20;
a comprising (i) a pharmaceutical composition of the anti-CEACAM5 immunoconjugate and (ii) one or more pharmaceutical compositions comprising TAS-102, in separate or combined formulations in copending claim 21.
Regarding instant claims 1-15, ‘443 taught pharmaceutical formulations of a CEACAM5 immunoconjugate conjugated to DM4 via a SPDB linker in copending claims 18-19, 31, and 37, wherein copending claim 37 the anti-CEACAM5 immunoconjugate consists of huMAb2-3-SPDB-DM4 and would be required to have a DAR of at least one (instant claims 1-15). ‘443 further taught methods of treating cancer with an anti-CEACAM5 immunoconjugate in copending claims 23, 25-26, and 37-39.
Regarding instant claims 1-15, ‘558 taught a method of treating cancer in a subject wherein an anti-CEACAM5 immunoconjugate conjugate of tusamitamab ravtansine is administered in copending claim 13 (instant claims 1-15).
‘558 further taught:
a method of treating cancer in a subject wherein an anti-CEACAM5 immunoconjugate is administered in combination with an anti-PD-1 or PD-L1 antibody in copending claims 1-2, 5, 10, 12-14, 23-24, 27, 30, and wherein the cancer is colorectal cancer in copending claim 17;
a method for treating cancer comprising administering the CEACAM5 immunoconjugate tusamitamab ravtansine in combination with an anti-PD-1 or PD-L1 antibody, wherein the dose of tusamitamab ravtansine is about 60 mg/m2 or 120 mg/m2 and 200 mg of pembrolizumab is used in copending claims 32, 34, and 39;
a method of treating cancer in a subject wherein an anti-CEACAM5 immunoconjugate is administered in combination with an anti-PD-1 or PD-L1 antibody in addition to chemotherapy in copending claims 43, 47, 50, 53, and 57, wherein copending claim 57 further taught administration of 120 mg/m2 tusamitamab ravtansine every 3 weeks.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 40-60 of copending Application No. 17/705,016. Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding instant claims 1-15, ‘016 taught methods of treating a patient comprising administering to the patient an antibody that binds CEACAM5, wherein the patient has a CEACAM5 expressing cancer in copending claims 40-47, methods of treating a patient comprising administering to the patient an immunoconjugate that binds CEACAM5, wherein the patient has a CEACAM5 expressing cancer in copending claims 48-60. Regarding instant claims 1-15, ‘016 taught methods of treating a patient comprising administering to the patient an immunoconjugate that binds CEACAM5, wherein the immunoconjugate comprises a heavy chain comprising an amino acid sequence of SEQ ID NO:87 and a light chain comprising an amino acid of SEQ ID NO:88 conjugated to DM4 via a SPDB linker, wherein the heavy and light chain are identical to instant SEQ ID NO:8 and 9, respectively, further the conjugate would be required to at least have a DAR of 1 (instant claim 1-15). The method would require the claimed immunoconjugate.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1, 5-7, 10, and 13-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1-31 and 36-40 of copending Application No. 18/043,715; or
claims 1-4, 8, 10-17, 19-26, 28, and 30-37 of copending Application No. 18/817,000.
Although the claims at issue are not identical, they are not patentably distinct from each other because:
Regarding instant claims 1, 5-7, 10, and 13-15, ‘715 taught an anti-CEACAM5 immunoconjugate comprising a cleavable linker cytostatic drug of formula V, wherein exatecan is a topoisomerase inhibitor in copending claim 26 which would be required to have a DAR of at least one. ‘715 further taught anti-CEACAM5 antibodies in copending claims 1-13, isolated nucleic acids of an anti-CEACAM5 antibody in copending claims 14-15, anti-CEACAM5 immunoconjugates in copending claims 16-31, and methods of treating cancer or detecting CEACAM5 by administering anti-CEACAM5 immunoconjugates in copending claims 37-40.
Regarding instant claims 1, 5-7, 10, and 13-15, ‘000 taught an anti-CEACAM5 immunoconjugate comprising a cleavable linker cytostatic drug with a structure of
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, wherein exatecan is a topoisomerase inhibitor in copending claim 20 which would be required to have a DAR of at least one. ‘000 further taught anti-CEACAM5 immunoconjugates pharmaceutical compositions in copending claims 1, 3-4, 8, 10, 12, 14-17, 19-23, 26, 28, and 30 and methods of treating cancer or preparing an anti-CEACAM5 immunoconjugate by administering anti-CEACAM5 immunoconjugates in copending claims 2, 11, 13, 24-25, and 31-37.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 1-24 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over:
claims 1-24 of copending Application No. 17/916,877;
claims 1-24 of copending Application No. 17/917,064;
claims 1-24 of copending Application No. 17/916,737; or
claims 1-2, 5, 10, 12-14, 17, 23-24, 27, 30, 32, 34, 39, 43, 47, 50, 53, and 57 of copending Application No. 18/715,558.
in view of US 20180022817 (Berne P-F et al. IDS reference), Jeon H-J et al. A (J Korean Soc Coloproctol. 2011 Jun 30;27(3):140–146) and NCT03324113 Clinical Trial (https://clinicaltrials.gov/study/NCT03324113?tab=history&a=10#version-content-panel Date 3/2019).
‘877, ‘064, ‘737, and ‘558 taught the limitations of claims 1-15 for the reasons set forth above.
‘877, ‘064, ‘737, ‘558, Berne, Jeon, and NCT03324113 are described above.
‘877, ‘064, ‘737, and ‘558 do not teach: 1) a treatment method comprising administering and immunoconjugate comprising an anti-CEACAM5-antibody in combination with FOLFOX; or 2) a pharmaceutical composition or kit of an anti-CEACAM5-antibody with FOLFOX specifically, but this is obvious in view of Berne, Jeon, and NCT03324113.
Regarding instant claims 16-24, it would have been obvious for a person having ordinary skill in the art to take the methods of
‘877 copending claims 12, 17, 19, and 24 for treating cancer comprising administering a CEACAM5 immunoconjugate and FOLFIRI, wherein the cancer is colorectal cancer, wherein the immunoconjugate comprising an anti-CEACAM5-antibody, and FOLFIRI are administered in 8 to 16 cycles, wherein one cycle comprises: administering the immunoconjugate at a dosage of from 60 to 210 mg/m2, at least once in the cycle; and administering FOLFIRI, wherein the CEACAM5 immunoconjugate is huMAb2-3-SPDB-DM4;
‘064 copending claims 12, 17, 19, and 24 for treating cancer comprising administering a CEACAM5 immunoconjugate and cetuximab, wherein the cancer is colorectal cancer, wherein the immunoconjugate comprising an anti-CEACAM5-antibody, and cetuximab are administered in 8 to 16 cycles, wherein one cycle comprises: administering the immunoconjugate at a dosage of from 60 to 210 mg/m2, at least once in the cycle; and administering cetuximab, wherein the CEACAM5 immunoconjugate is huMAb2-3-SPDB-DM4
‘737 copending claims 12, 17, 19, and 24 for treating cancer comprising administering a CEACAM5 immunoconjugate and TAS-102, wherein the cancer is colorectal cancer, wherein the immunoconjugate comprising an anti-CEACAM5-antibody, and FOLFIRI are administered in 8 to 16 cycles, wherein one cycle comprises: administering the immunoconjugate at a dosage of from 60 to 210 mg/m2, at least once in the cycle; and administering TAS-102, wherein the CEACAM5 immunoconjugate is huMAb2-3-SPDB-DM4; or
‘558 copending claims 17 and 57 for a method of treating cancer in a subject wherein an anti-CEACAM5 immunoconjugate is administered in combination with an anti-PD-1 or PD-L1 antibody in addition to another platinum chemotherapeutic agent, wherein the dose of tusamitamab ravtansine is 120 mg/m2 every 3 weeks
– and further: 1) prepare a pharmaceutical composition with the CAECAM5 immunoconjugate and exchange FOLFIRI, cetuximab, TAS-102, or the platinum chemotherapeutic agent of ‘877, ‘064, ‘737, or ‘558 for FOLFOX as a separate pharmaceutical composition for the treatment; 2) administer the pharmaceutical composition comprising the CEACAM5 immunoconjugate and FOLFOX at 200 mg/m2 leucovorin (LV), 1000 mg/m2 5-fluorouracil (5-FU), and 85 mg/m2 oxaliplatin at least once per cycle; and 3) prepare a kit of the pharmaceutical composition comprising the immunoconjugate and FOLFOX.
This is obvious because: 1-2a) Jeon taught chemotherapy using the FOLFOX regimen is effective and tolerable in patients with colon cancer, wherein the FOLFOX regimen consisted of administering 200 mg/m2 leucovorin (LV), 1000 mg/m2 5-fluorouracil (5-FU), and 85 mg/m2 oxaliplatin to colon cancer patients at least once per cycle for 10 to 12 cycles; 1-2b) Berne taught huMAb2-3-SPDB-DM4 is a results effective variable for colorectal cancer treatment and that a person having ordinary skill in the art can determine the appropriate dose. Thus it would be obvious to exchange one colon cancer therapeutic for another effective one for combination therapy with huMAb2-3-SPDB-DM4; and 3) Berne taught the immunoconjugate in a kit and a single kit would allow all components of treatment to be packaged together for easier ordering and tracking.
There is a reasonable expectation of success because: 1-2a) Jeon taught chemotherapy using the FOLFOX regimen is effective and tolerable in patients with colon cancer, wherein the FOLFOX regimen consisted of administering 200 mg/m2 leucovorin (LV), 1000 mg/m2 5-fluorouracil (5-FU), and 85 mg/m2 oxaliplatin to colon cancer patients at least once per cycle for 10 to 12 cycles; 1-2b) Berne taught huMAb2-3-SPDB-DM4 is effective for treating subjects with colorectal cancer and huMAb2-3-SPDB-DM4 is a results effective variable for colorectal cancer treatment and that a person having ordinary skill in the art can determine the appropriate dose. Thus exchange of one colon cancer therapeutic for another effective one for combination therapy with huMAb2-3-SPDB-DM4 would have a reasonable expectation of success; and 3) a single kit would allow all components of treatment to be packaged together for easier ordering and tracking.
This would produce an effective method of treating subjects with human colorectal cancer comprising preparing then administering in 8 to 16 cycles, wherein one cycle comprises a pharmaceutical composition comprising at least two separate pharmaceutical compositions of:
60-210 or 120 mg/m2 huMAb2-3-SPDB-DM4 and a pharmaceutically acceptable excipient at least once a cycle; and
FOLFOX comprising 200 mg/m2 leucovorin (LV), 1000 mg/m2 5-fluorouracil (5-FU), and 85 mg/m2 oxaliplatin and a pharmaceutically acceptable excipient at least once a cycle,
to subjects in need thereof (instant claims 16-20, 22, and 24), wherein the pharmaceutical composition is prepared as huMAb2-3-SPDB-DM4 and a pharmaceutically acceptable excipient and FOLFOX as a separate pharmaceutical composition for the treatment, and wherein the pharmaceutical composition comprising huMAb2-3-SPDB-DM4 and FOLFOX are in a kit prior to administration (instant claims 21 and 23).
This is a provisional nonstatutory double patenting rejection.
Conclusion
Claims 1-24 are rejected.
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/J.J.S./Examiner, Art Unit 1643
/JULIE WU/Supervisory Patent Examiner, Art Unit 1643