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
The Amendments and Remarks filed 5/14/26 in response to the Office Action of 2/18/26 are acknowledged and have been entered.
Claims 1, 4, 10, 14, 19, 22-24, 28-30, 34, 40, 45, 47, 51, 69, 73, 74, and 80 are pending.
Claims 34 and 45 have been amended by Applicant.
Claims 1, 4, 10, 14, 19, 22-24, 28-30, 34, 40, 45, 47, 51, 69, 73, 74, and 80 are currently under examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Rejections Withdrawn
The rejections under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 103
Claims 1, 4, 10, 14, 19, 22-24, 28-30, 34, 40, 45, 47, 51, 69, 73, 74, and 80 are rejected under 35 U.S.C. 103(a) as being unpatentable over Altintas et al (US 2020/0062853 A1; 2/27/2020).
Instant claims 73-74 are drawn to compositions comprising amounts of bispecific antibodies of Altintas et al. Instant claims 4, 10, 14, 19, 22-24, 28-30, 34, 40, 45, 47, 51, 69, and 80 are drawn to methods of reducing or preventing progression of a tumor or treating cancer comprising administering the bispecific antibodies of Altintas et al to human subjects at recited dosing cycles and/or at recited amounts. It is further noted: US 12077596 B2 is a patent that is a divisional of Altintas et al comprising patented claims to methods of treating cancer in subjects comprising administering recited antibodies to the subjects.
Altintas et al teaches bispecific antibodies comprising a first binding region to human CD40 and a second binding region to human CD137 ([0055], in particular). Altintas et al further teaches the bispecific antibodies as comprising a first heavy chain (HC) polypeptide comprising a first VH region comprising SEQ ID NO:117 (same as instant SEQ ID NO:9) and first CH region; a first light chain (LC) polypeptide comprising a first VL region comprising SEQ ID NO:121 (same as instant SEQ ID NO:10) and a first CL region; a second heavy chain (HC) polypeptide comprising a second VH region comprising SEQ ID NO:123 (same as instant SEQ ID NO:19) and a second CH region; and a second light chain (LC) polypeptide comprising a second VL region and a second CL region comprising SEQ ID NO:127 (same as instant SEQ ID NO:20) ([0441]-[0443], in particular). Altintas et al further teaches the bispecific antibodies as comprising hinge, CH2, and CH3 regions in each heavy chain ([0120], in particular). Altintas et al further teaches the bispecific antibodies as comprising asymmetrical mutations in said CH3 regions ([0120], in particular). Altintas et al further teaches the bispecific antibodies wherein (a) the position corresponding to F405 in a human IgG1 heavy chain according to EU numbering of the first CH is L, and the position corresponding to K409 in a human IgG1 heavy chain according to EU numbering of the second CH chain is R; or (b) the position corresponding to K409 in a human IgG1 heavy chain according to EU numbering of the first CH chain is R, and the position corresponding to F405 in a human IgG1 heavy chain according to EU numbering of the second CH chain is L ([0446], in particular). Altintas et al further teaches the bispecific antibodies wherein said first and second heavy chains are modified so that the bispecific antibodies induce and/or enhances Fc-mediated effector function to a lesser extent compared to a bispecific antibody which is identical except for comprising non-modified first and second heavy chains ([0579], in particular). Altintas et al further teaches the bispecific antibodies wherein the modified heavy chains have reduced C1q binding as compared to wild-type antibody ([0581], in particular). Altintas et al further teaches the bispecific antibodies wherein in at least one of said first and second heavy chains one or more amino acids in the positions corresponding to positions L234, L235, D265, N297, and P331 in a human IgG1 heavy chain according to EU numbering, are not L, L, D, N, and P, respectively ([0592], in particular). Altintas et al further teaches the bispecific antibodies wherein in at least one of said first and second heavy chains the amino acids in the positions corresponding to positions L234 and L235 in a human IgG1 heavy chain according to EU numbering, are F and E; or A and A, respectively ([0656], in particular). Altintas et al further teaches the bispecific antibodies wherein the positions corresponding to positions L234, L235, and D265 in the human IgG1 heavy chain of SEQ ID NO:109 (same as instant SEQ ID NO:21) of both the first heavy chain and the second heavy chain are F, E, and A, respectively. Altintas et al further teaches the bispecific antibodies wherein a LC comprises SEQ ID NO:114 ([0740], in particular; identical to instant SEQ ID NO:27), which is a kappa constant region Table 1, in particular). Altintas et al further teaches the bispecific antibodies as IgG1 ([0116], in particular). Altintas et al further teaches methods of treating cancer comprising administering the bispecific antibodies to subjects with cancer ([0003], [0825], and [0835]-[0837], in particular). Altintas et al further teaches said methods wherein the bispecific antibodies are administered by any suitable route, including intravenously ([0807], in particular). Altintas et al further teaches said methods wherein the cancer is a solid cancerous tumor, such as breast cancer ([0813], in particular). Altintas et al further teaches dosages used in said method should be optimized ([0845], in particular). Altintas et al further teaches dosages and dosage regimens for the bispecific antibodies depend on disease or condition to be treated and may be determined by persons skilled in the art ([0846], in particular). Altintas et al further teaches 0.001-30 mg/kg as an exemplary, non-limiting range for a therapeutically effective amount of the bispecific antibodies ([0846], in particular). Altintas et al further teaches the bispecific antibodies may be administered by infusion in a weekly dosage of calculated by mg/m2 and/or such doses can be based on the mg/kg dosages provided above according to the following: dose (mg/kg)×70: 1.8 and that such administration may be repeated, e.g., 1 to 8 times, such as 3 to 5 times ([0847], in particular). Altintas et al further teaches the bispecific antibodies may be administered in a weekly dosage of calculated as a fixed dose for up to 8 times, such as from 4 to 6 times when given once a week and such regimen may be repeated one or more times as necessary, for example, after 6 months or 12 months ([0848], in particular).
Altintas et al does not specifically demonstrate administering the bispecific antibodies to subjects at recited doses and/or dosing cycles. However, one of skill in the art would have been motivated with an expectation of success to perform the method of Altintas et al wherein the subject is just any subject with cancer of Altintas et al and the method comprises intravenously administering at any doses of the bispecific antibodies (including any doses between 0.001-30 mg/kg; 0.07-2100 mg for a 70 kg subject) and/or dosing schedules (including weekly for 8 weeks) encompassed by those of Altintas et al. “[W]here the general conditions of a claims are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456 (CCPA 1955) (Citing In re Dreyfus, 73 F.2d 931 (CCPA 1934); In re Waite, 168 F.2d 104 (CCPA 1948)). MPEP 2144.05 states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” In the instant case, given the expected therapeutic benefit of the bispecific antibodies , it is well within the level of the ordinary skilled artisan to adjust the dosages and timing of administration for optimal therapeutic efficacy and safety, and to arrive at the dosages and timing of administration instantly claimed, where the combination is expected to provide therapeutic cancer treatment. Further, varying dosage amounts and dosage schedules of the administered bispecific antibodies of the method are “result-effective variables” wherein the results are therapeutic benefit weighed against dose-limiting toxicities and the variables are the varying amounts and dosage schedules of the administered bispecific antibodies. Further, this is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference to arrive at the claimed invention. See MPEP 2143. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Response to Arguments
In the Reply of 5/14/26, Applicant argues Altintas et al does not teach a dose range for human cancer patients as recited in the claims. Applicant further cites various references that question effectiveness and/or safety of bispecific antibodies that bind recited targets, cites various references using mouse models that do not teach dose amounts or particular characteristics for a human subject having a tumor, and argues that the dose range of 0.001 to 30 mg/kg of Altintas et al, at best, can be considered an invitation for the skilled person to perform a study to find a pharmaceutically active and safe dose amounts for the bispecific binding agent in human patients and does not provide any reasonable expectation of success that such dose amounts may in fact be available. Applicant further cites Example 4 and Figs. 6A, 6B, 7, 8A, 8B, 9A, and 9B of the instant specification and indicates the claims are non-obvious because the specification demonstrates particularly favorable antitumor immune responses, such as transient trafficking/margination of CD8+ T cells B cells, CD4+ and CD8+ effector memory T cell maturation/expansion, and proliferation and activation of total CD8+ T cells and CD8+ effector memory cells was obtained at doses ranging from 300-200 mg. Applicant further cites Example 2 of the instant specification and indicates a dose higher than 200 mg is associated with higher instances of treatment-related serious adverse events (SAEs) and grade ≥3 AEs.
The amendments to the claims and the arguments found in the Reply of 5/14/26 have been carefully considered, but are not deemed persuasive. In regards to the argument Altintas et al does not teach a dose range for human cancer patients as recited in the claims, instant claim 1 recites 0.04-2.5 mg/kg body weight or 3-200 mg as amounts of the bispecific antibodies that is administered to a human subject. For a 70 kg human subject, that recited 0.04-2.5 mg/kg would be 2.8-175 mg. The composition claim of instant claim 73 recites 3-200 mg as an amount of the bispecific antibodies. Altintas et al teaches the recited bispecific antibodies are specific for human CD40 and human CD137 (Abstract, in particular) that are to be administered to subjects with cancer ([0003], [0825], and [0835]-[0837], in particular) and teaches 0.001-30 mg/kg body weight as an exemplary, non-limiting, range for a therapeutically effective amount of the bispecific antibodies ([0846], in particular). At [0848] of Altintas teaches 70 kg as an exemplary body weight. At 0.001-30 mg/kg body weight, a 70 kg human subject would be administered at an amount of 0.07-2100 mg. An amount of 0.07-2100 mg for a 70 kg subject of Altintas overlaps with both (i) an amount of 0.04-2.5 mg/kg body weight for a 70 kg subject (2.8-175 mg) and 3-200 mg of instant claim 1 and (ii) an amount of 3-200 mg of the composition of instant claim 73. See MPEP 2144.05: In the case where the claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990) (The prior art taught carbon monoxide concentrations of "about 1-5%" while the claim was limited to "more than 5%." The court held that "about 1-5%" allowed for concentrations slightly above 5% thus the ranges overlapped.); In re Geisler, 116 F.3d 1465, 1469-71, 43 USPQ2d 1362, 1365-66 (Fed. Cir. 1997) (Claim reciting thickness of a protective layer as falling within a range of "50 to 100 Angstroms" considered prima facie obvious in view of prior art reference teaching that "for suitable protection, the thickness of the protective layer should be not less than about 10 nm [i.e., 100 Angstroms]." The court stated that "by stating that ‘suitable protection’ is provided if the protective layer is ‘about’ 100 Angstroms thick, [the prior art reference] directly teaches the use of a thickness within [applicant’s] claimed range."). See also In re Bergen, 120 F.2d 329, 332, 49 USPQ 749, 751-52 (CCPA 1941) (The court found that the overlapping endpoint of the prior art and claimed range was sufficient to support an obviousness rejection, particularly when there was no showing of criticality of the claimed range).
In regards to the citation of various references that question effectiveness and/or safety of bispecific antibodies that bind recited targets, citation of various references using mouse models that do not teach dose amounts or particular characteristics for a human subject having a tumor, and argument that the dose range of 0.001 to 30 mg/kg of Altintas et al, at best, can be considered an invitation for the skilled person to perform a study to find a pharmaceutically active and safe dose amounts for the bispecific binding agent in human patients and does not provide any reasonable expectation of success that such dose amounts may in fact be available, the examiner disagrees. Altintas et al is much more than an invitation for the skilled person to perform a study to find a pharmaceutically active and safe dose amounts for the bispecific binding agent in human patients. Altintas et al clearly teaches antibodies of the compositions of claim 73, Altintas et al teaches the antibodies target human proteins, Altintas et al teaches treating cancers in subjects comprising administering said antibodies, and suggests dosage amounts of the antibodies that overlap with amounts of the instant claims (citations above). Where claimed ranges "overlap or lie inside ranges disclosed by the prior art" a prima facie case of obviousness exists. Where there is a reason to modify the prior art to achieve the claimed invention, the claims may be rejected as prima facie obvious provided there is also a reasonable expectation of success. Obviousness does not require absolute predictability, but at least some degree of predictability is required. Conclusive proof of efficacy is not required to show a reasonable expectation of success. OSI Pharm., LLC v. Apotex Inc., 939 F.3d 1375, 1385, 2019 USPQ2d 379681 (Fed. Cir. 2019) ("To be clear, we do not hold today that efficacy data is always required for a reasonable expectation of success. Nor are we requiring ‘absolute predictability of success.’"); Acorda Therapeutics, Inc. v. Roxane Lab., Inc., 903 F.3d 1310, 1333, 128 USPQ2d 1001, 1018 (Fed. Cir. 2018) ("This court has long rejected a requirement of ‘[c]onclusive proof of efficacy’ for obviousness." (citing to Hoffmann-La Roche Inc. v. Apotex Inc., 748 F.3d 1326, 1331 (Fed. Cir. 2014); PharmaStem Therapeutics, Inc. v. ViaCell, Inc., 491 F.3d 1342, 1364 (Fed. Cir. 2007); Pfizer, Inc. v. Apotex, Inc., 480 F.3d 1348, 1364, 1367–68 (Fed. Cir. 2007) (reasoning that "the expectation of success need only be reasonable, not absolute")). See MPEP 2143.02. Further, US 12077596 B2 is a patent that is a divisional of Altintas et al comprising patented claims to methods of treating cancer in subjects comprising administering recited antibodies to the subjects.
In regards to the citation of Example 4 and Figs. 6A, 6B, 7, 8A, 8B, 9A, and 9B of the instant specification and indication the claims are non-obvious because the specification demonstrates particularly favorable antitumor immune responses, such as transient trafficking/margination of CD8+ T cells B cells, CD4+ and CD8+ effector memory T cell maturation/expansion, and proliferation and activation of total CD8+ T cells and CD8+ effector memory cells was obtained at doses ranging from 30-200 mg, it is first noted that instant claims 73-74 are product claims. Further, antitumor immune responses from administering the recited antibodies are reasonably predictable because Altintas et al teaches the recited antibodies induce T cell proliferation (Figs. 8-11 and Examples 5-6, in particular) and expand tumor infiltrating lymphocytes (TILs) obtained from numerous cancer tissue types (Figs. 12-13 and Example 11, in particular). A sufficient number of tests both inside and outside the claimed range have not been provided to demonstrate criticality of the claimed range. To establish unexpected results over a claimed range, applicants should compare a sufficient number of tests both inside and outside the claimed range to show the criticality of the claimed range. In re Hill, 284 F.2d 955, 128 USPQ 197 (CCPA 1960). See MPEP 716.02(d).
In regards to the citation of Example 2 of the instant specification and indication a dose higher than 200 mg is associated with higher instances of treatment-related serious adverse events (SAEs) and grade ≥3 AEs, the instant specification discloses three subjects (one with a 100 mg dose encompassed by the claims and two with a 200 mg dose encompassed by the claims) exhibited grade ≥3 AEs ([0490]-[0493] and Table 10, in particular). Instant Table 10 further teaches none of the seven patients treated with dosages outside the claimed ranges (˂1 mg or 400 mg) exhibited SAEs. Therefore, criticality of the claimed range for avoiding SAEs has not been demonstrated. Table 10:
PNG
media_image1.png
261
867
media_image1.png
Greyscale
Double Patenting
Claims 1, 4, 10, 14, 19, 22-24, 28-30, 34, 40, 45, 47, 51, 69, 73, 74, and 80 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11091557 B2 in view of Altintas et al (US 2020/0062853 A1; 2/27/2020). The patent claims are drawn to a method for making the bispecific antibodies of Altintas et al; the patent claims do not recite administering the bispecific antibodies at recited doses and/or dosing times. However, one of skill in the art would have been motivated with an expectation of success to perform the patented method to generate bispecific antibodies for the method of Altinas et al and then perform the method of Altinta et al with the bispecific antibodies wherein the subject is just any subject with cancer of Altinta et al and the method comprises intravenously administering at any doses of the bispecific antibodies (including any doses between 0.001-30 mg/kg; 0.07-210 mg for a 70 kg subject) and/or dosing schedules (including weekly for 8 weeks) encompassed by those of Altinta et al. “[W]here the general conditions of a claims are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456 (CCPA 1955) (Citing In re Dreyfus, 73 F.2d 931 (CCPA 1934); In re Waite, 168 F.2d 104 (CCPA 1948)). MPEP 2144.05 states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” In the instant case, given the expected therapeutic benefit of the bispecific antibodies , it is well within the level of the ordinary skilled artisan to adjust the dosages and timing of administration for optimal therapeutic efficacy and safety, and to arrive at the dosages and timing of administration instantly claimed, where the combination is expected to provide therapeutic cancer treatment. Further, varying dosage amounts and dosage schedules of the administered bispecific antibodies of the method are “result-effective variables” wherein the results are therapeutic benefit weighed against dose-limiting toxicities and the variables are the varying amounts and dosage schedules of the administered bispecific antibodies.
Response to Arguments
In the Reply of 5/14/26, Applicant repeats arguments addressed above.
Double Patenting
Claims 1, 4, 10, 14, 19, 22-24, 28-30, 34, 40, 45, 47, 51, 69, 73, 74, and 80 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-11 of U.S. Patent No. 11084882 B2 in view of Altintas et al (US 2020/0062853 A1; 2/27/2020). The patent claims are drawn to the bispecific antibodies of Altintas et al; the patent claims do not recite administering the bispecific antibodies at recited doses and/or dosing times. However, one of skill in the art would have been motivated with an expectation of success to perform the method of Altinta et al with the bispecific antibodies of the patent (same as those of Altina et al) wherein the subject is just any subject with cancer of Altinta et al and the method comprises intravenously administering at any doses of the bispecific antibodies (including any doses between 0.001-30 mg/kg; 0.07-210 mg for a 70 kg subject) and/or dosing schedules (including weekly for 8 weeks) encompassed by those of Altinta et al. “[W]here the general conditions of a claims are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456 (CCPA 1955) (Citing In re Dreyfus, 73 F.2d 931 (CCPA 1934); In re Waite, 168 F.2d 104 (CCPA 1948)). MPEP 2144.05 states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” In the instant case, given the expected therapeutic benefit of the bispecific antibodies , it is well within the level of the ordinary skilled artisan to adjust the dosages and timing of administration for optimal therapeutic efficacy and safety, and to arrive at the dosages and timing of administration instantly claimed, where the combination is expected to provide therapeutic cancer treatment. Further, varying dosage amounts and dosage schedules of the administered bispecific antibodies of the method are “result-effective variables” wherein the results are therapeutic benefit weighed against dose-limiting toxicities and the variables are the varying amounts and dosage schedules of the administered bispecific antibodies.
Response to Arguments
In the Reply of 5/14/26, Applicant repeats arguments addressed above.
Double Patenting
Claims 1, 4, 10, 14, 19, 22-24, 28-30, 34, 40, 45, 47, 51, 69, 73, 74, and 80 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11440966 B2 in view of Altintas et al (US 2020/0062853 A1; 2/27/2020). The patent claims are drawn to the bispecific antibodies of Altintas et al; the patent claims do not recite administering the bispecific antibodies at recited doses and/or dosing times. However, one of skill in the art would have been motivated with an expectation of success to perform the method of Altinta et al with the bispecific antibodies of the patent (same as those of Altina et al) wherein the subject is just any subject with cancer of Altinta et al and the method comprises intravenously administering at any doses of the bispecific antibodies (including any doses between 0.001-30 mg/kg; 0.07-210 mg for a 70 kg subject) and/or dosing schedules (including weekly for 8 weeks) encompassed by those of Altinta et al. “[W]here the general conditions of a claims are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456 (CCPA 1955) (Citing In re Dreyfus, 73 F.2d 931 (CCPA 1934); In re Waite, 168 F.2d 104 (CCPA 1948)). MPEP 2144.05 states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” In the instant case, given the expected therapeutic benefit of the bispecific antibodies , it is well within the level of the ordinary skilled artisan to adjust the dosages and timing of administration for optimal therapeutic efficacy and safety, and to arrive at the dosages and timing of administration instantly claimed, where the combination is expected to provide therapeutic cancer treatment. Further, varying dosage amounts and dosage schedules of the administered bispecific antibodies of the method are “result-effective variables” wherein the results are therapeutic benefit weighed against dose-limiting toxicities and the variables are the varying amounts and dosage schedules of the administered bispecific antibodies.
Response to Arguments
In the Reply of 5/14/26, Applicant repeats arguments addressed above.
Double Patenting
Claims 1, 4, 10, 14, 19, 22-24, 28-30, 34, 40, 45, 47, 51, 69, 73, 74, and 80 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 11939388 B2 in view of Altintas et al (US 2020/0062853 A1; 2/27/2020). The patent claims are drawn to nucleic acid encoding the bispecific antibodies of Altintas et al and host cells comprising expression vectors comprising said nucleic acid; the patent claims do not recite administering the bispecific antibodies at recited doses and/or dosing times. However, one of skill in the art would have been motivated with an expectation of success to use the host cells expressing the bispecific bispecific antibodies of the copending claims to generate the bispecific antibodies and then perform the method of Altinta et al with the bispecific antibodies wherein the subject is just any subject with cancer of Altinta et al and the method comprises intravenously administering at any doses of the bispecific antibodies (including any doses between 0.001-30 mg/kg; 0.07-210 mg for a 70 kg subject) and/or dosing schedules (including weekly for 8 weeks) encompassed by those of Altinta et al. “[W]here the general conditions of a claims are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456 (CCPA 1955) (Citing In re Dreyfus, 73 F.2d 931 (CCPA 1934); In re Waite, 168 F.2d 104 (CCPA 1948)). MPEP 2144.05 states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” In the instant case, given the expected therapeutic benefit of the bispecific antibodies , it is well within the level of the ordinary skilled artisan to adjust the dosages and timing of administration for optimal therapeutic efficacy and safety, and to arrive at the dosages and timing of administration instantly claimed, where the combination is expected to provide therapeutic cancer treatment. Further, varying dosage amounts and dosage schedules of the administered bispecific antibodies of the method are “result-effective variables” wherein the results are therapeutic benefit weighed against dose-limiting toxicities and the variables are the varying amounts and dosage schedules of the administered bispecific antibodies.
Response to Arguments
In the Reply of 5/14/26, Applicant repeats arguments addressed above.
Double Patenting
Claims 1, 4, 10, 14, 19, 22-24, 28-30, 34, 40, 45, 47, 51, 69, 73, 74, and 80 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 12077596 B2 in view of Altintas et al (US 2020/0062853 A1; 2/27/2020). The patent claims are drawn to methods of administering the bispecific antibodies of Altintas et al; the patent claims do not recite administering the bispecific antibodies at recited doses and/or dosing times. However, one of skill in the art would have been motivated with an expectation of success to perform the method of Altinta et al with the bispecific antibodies wherein the subject is just any subject with cancer of Altinta et al and the method comprises intravenously administering at any doses of the bispecific antibodies (including any doses between 0.001-30 mg/kg; 0.07-210 mg for a 70 kg subject) and/or dosing schedules (including weekly for 8 weeks) encompassed by those of Altinta et al. “[W]here the general conditions of a claims are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456 (CCPA 1955) (Citing In re Dreyfus, 73 F.2d 931 (CCPA 1934); In re Waite, 168 F.2d 104 (CCPA 1948)). MPEP 2144.05 states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” In the instant case, given the expected therapeutic benefit of the bispecific antibodies , it is well within the level of the ordinary skilled artisan to adjust the dosages and timing of administration for optimal therapeutic efficacy and safety, and to arrive at the dosages and timing of administration instantly claimed, where the combination is expected to provide therapeutic cancer treatment. Further, varying dosage amounts and dosage schedules of the administered bispecific antibodies of the method are “result-effective variables” wherein the results are therapeutic benefit weighed against dose-limiting toxicities and the variables are the varying amounts and dosage schedules of the administered bispecific antibodies.
Response to Arguments
In the Reply of 5/14/26, Applicant repeats arguments addressed above.
Double Patenting
Claims 1, 4, 10, 14, 19, 22-24, 28-30, 34, 40, 45, 47, 51, 69, 73, 74, and 80 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 6, 15, 42, 47, 81, 83-90, and 92-95 of copending Application No. 17/817033 in view of Altintas et al (US 2020/0062853 A1; 2/27/2020). The copending claims are drawn to bispecific antibodies of Altintas et al; the copending claims do not recite administering the bispecific antibodies at recited doses and/or dosing times. However, one of skill in the art would have been motivated with an expectation of success to perform the method of Altinta et al with the bispecific antibodies wherein the subject is just any subject with cancer of Altinta et al and the method comprises intravenously administering at any doses of the bispecific antibodies (including any doses between 0.001-30 mg/kg; 0.07-210 mg for a 70 kg subject) and/or dosing schedules (including weekly for 8 weeks) encompassed by those of Altinta et al. “[W]here the general conditions of a claims are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456 (CCPA 1955) (Citing In re Dreyfus, 73 F.2d 931 (CCPA 1934); In re Waite, 168 F.2d 104 (CCPA 1948)). MPEP 2144.05 states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” In the instant case, given the expected therapeutic benefit of the bispecific antibodies , it is well within the level of the ordinary skilled artisan to adjust the dosages and timing of administration for optimal therapeutic efficacy and safety, and to arrive at the dosages and timing of administration instantly claimed, where the combination is expected to provide therapeutic cancer treatment. Further, varying dosage amounts and dosage schedules of the administered bispecific antibodies of the method are “result-effective variables” wherein the results are therapeutic benefit weighed against dose-limiting toxicities and the variables are the varying amounts and dosage schedules of the administered bispecific antibodies.
This is a provisional nonstatutory double patenting rejection.
Response to Arguments
In the Reply of 5/14/26, Applicant repeats arguments addressed above.
Double Patenting
Claims 1, 4, 10, 14, 19, 22-24, 28-30, 34, 40, 45, 47, 51, 69, 73, 74, and 80 remain provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 11, 15, 20, 23, 24, 26, 30, 35, 41, 46, 48, 70, 74, 78, 79, 81, 85, and 86 of copending Application No. 18/579086 in view of Altintas et al (US 2020/0062853 A1; 2/27/2020). The copending claims are drawn to bispecific antibodies of Altintas et al and methods comprising those of Altintas et al; the copending claims do not recite administering the bispecific antibodies at recited doses and/or dosing times. However, one of skill in the art would have been motivated with an expectation of success to perform the method of Altinta et al with the bispecific antibodies wherein the subject is just any subject with cancer of Altinta et al and the method comprises intravenously administering at any doses of the bispecific antibodies (including any doses between 0.001-30 mg/kg; 0.07-210 mg for a 70 kg subject) and/or dosing schedules (including weekly for 8 weeks) encompassed by those of Altinta et al. “[W]here the general conditions of a claims are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456 (CCPA 1955) (Citing In re Dreyfus, 73 F.2d 931 (CCPA 1934); In re Waite, 168 F.2d 104 (CCPA 1948)). MPEP 2144.05 states: “Generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical.” In the instant case, given the expected therapeutic benefit of the bispecific antibodies , it is well within the level of the ordinary skilled artisan to adjust the dosages and timing of administration for optimal therapeutic efficacy and safety, and to arrive at the dosages and timing of administration instantly claimed, where the combination is expected to provide therapeutic cancer treatment. Further, varying dosage amounts and dosage schedules of the administered bispecific antibodies of the method are “result-effective variables” wherein the results are therapeutic benefit weighed against dose-limiting toxicities and the variables are the varying amounts and dosage schedules of the administered bispecific antibodies.
This is a provisional nonstatutory double patenting rejection.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SEAN E AEDER whose telephone number is (571)272-8787. The examiner can normally be reached M-F 9am-6pm ET.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Samira Jean-Louis can be reached at (571)270-3503. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/SEAN E AEDER/Primary Examiner, Art Unit 1642
Prosecution Insights