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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 9/8/2025 has been entered.
The following rejections are under section 103 are maintained:
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.
Claims 1-9, 12, 14, 15 and 19 remain rejected under 35 U.S.C. 103 as being unpatentable over Cui et al., Blood (2013) 122 (21): 1637 (Cui) as evidenced by WO 2019122447 (WO 447) in view of Jain et al., Pharm Res (2015) 32:3526–3540 (Jain).
Cui teaches that ROR1 has restricted expression on human malignancies, we have generated a series of monoclonal antibodies (mAb) against the extracellular domain of human ROR1 and are advancing a lead candidate mAb UC-961 (cirmtuzumab) into human clinical trials. Cui teaches a conjugate that is anti-ROR1 Cirmtuzumab stably bound to a modified monomethyl auristatin E (MMAE) through a light chain, constant region, lysine-linker with an antibody-drug ratio (ADR) of 2.5 (designated UC-961ADC3).
WO 447 teaches that UC-961 is the instant antibody with Heavy Chain SEQ ID NO: 98 and Light Chain SEQ ID NO: 99 corresponding to the instant Heavy and Light Chains SEQ ID NOS: 1 and 2, respectively, see page 65.
Cui may fail to teach the instant linkers required by the claims. However, Jain demonstrates that MC-VC-PAB-MMAE is a common linker payload group, which is commonly used since it is protease-active and effective in cancer treatment:
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In this way, those of ordinary skill could have applied this linker-drug in the manner required and in a predictable fashion for the purposes of obtaining the recited antibody-drug conjugate (ADC). As outlined above, the primary references teach ROR1 as a target for cancer immunotherapy. Cui also teaches anti-ROR1 antibody-drug conjugates comprising Cirmtuzumab (UC-961) stably bound to auristatin E (MMAE). Jain is added for the proposition that MC-VC-PAB is applicable to these conjugates. Specifically, Jain teaches that the particular known technique of using MC-VC-PAB was recognized as part of the ordinary capabilities of one skilled in the art. In this manner, those of ordinary skill would have recognized that applying the known technique to conjugates targeting ROR1, such as Cirmtuzumab would have yielded predictable results. Accordingly, conjugating MC-VC-PAB-MMAE to UC-961) would have been prima facie obvious.
The claims also require effective amounts and regimens. However, the amount of the recited conjugate as an effective dose is a result-effective parameter that will affect the pharmacological and pharmacokinetic properties of the final composition. In this manner, the amount of a specific ingredient in a composition is clearly a result-effective parameter that a person of ordinary skill in the art would routinely optimize.
Specifically, it would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve a desired result. For any compound, the therapeutically effective dose can be estimated initially either in cell culture assays or in animal models, usually rats, rabbits, dogs, or pigs. The animal model also can be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans.
Therapeutic efficacy and toxicity, e.g., ED50 (the dose therapeutically effective in 50% of the population) and LD50 (the dose lethal to 50% of the population), can be determined by standard pharmaceutical procedures in cell cultures or experimental animals. The dose ratio of toxic to therapeutic effects is the therapeutic index, and it can be expressed as the ratio, LD50/ED5o. Pharmaceutical compositions which exhibit large therapeutic indices are preferred. The data obtained from cell culture assays and animal studies is used in formulating a range of dosage for human use. The dosage contained in such compositions is preferably within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage varies within this range depending upon the dosage form employed, sensitivity of the patient, and the route of administration. The exact dosage will be determined by the practitioner, in light of factors related to the subject that requires treatment. Dosage and administration are adjusted to provide sufficient levels of the active ingredient or to maintain the desired effect. Factors which can be taken into account include the severity of the disease state, general health of the subject, age, weight, and gender of the subject, diet, time and frequency of administration, drug combination(s), reaction sensitivities, and tolerance/response to therapy. Long-acting pharmaceutical compositions can be administered once or twice daily every 3 to 4 days, every week, or once every two weeks depending on the half-life and clearance rate of the particular formulation.
Normal dosage amounts can vary from micrograms to 100,000 micrograms, up to a maximum total dose, depending upon the route of administration. Guidance as to particular dosages and methods of delivery is provided in the literature and generally available to practitioners in the art.
In this way, optimization of these parameters is a routine practice, and consequently, would be prima facie obvious, absent factual evidence demonstrating an unexpected benefit of the claimed amount(s).
Those of ordinary skill would have a reasonable expectation that the conjugate can treat the recited cancer since Cui teaches cytotoxic activity of each of the various cirmtuzumab-ADC against ROR1 on human malignancies.
Any observed pharmacological effects (see claim 15 and 16 i.e., eradication) would have been a necessary aspect of the conjugates, see MPEP 2112.01 (“Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”).
Applicant argues that the applied references do not enable the instant ADC, and that the references do not teach the required DAR.
WO 447 teaches that UC-961, as disclosed by Cui is the instant antibody with Heavy Chain SEQ ID NO: 98 and Light Chain SEQ ID NO: 99 corresponding to the instant Heavy and Light Chains SEQ ID NOS: 1 and 2, respectively, see page 65. Therefore, CUI is enabling for the instant ADC.
With regard to DAR, there are a limited and finite number of DAR’s for a given antibody- drug conjugate (ADC), around 8. Optimization of the DAR is a critical part of ADC development, since the DAR value affects the efficacy of the drug, as low drug loading reduces the potency, while high drug loading can negatively affect pharmacokinetics (PK)1 and toxicity. At the time the invention was made, easy, accurate and reproducible DAR calculation of ADC’s was within the
purview of those of ordinary skill.
In this manner, it would have been obvious to one have ordinary skill in the art at the time that applicant’s inventions was made to have made ADC’s with the recited DAR with a reasonable expectation that the resulting ADC with a DAR of 2 would be useful in treating cancer. In this connection, it is well-settled that ADC’s with a DAR from 1-8 are well within the purview of those of ordinary skill; and it would have been obvious to one of ordinary skill in the art at the time the invention was made to choose from this finite number of DAR options with a reasonable expectation of success of producing a ADC functional with a functional DAR.
Specifically, it is well within the skill of the artisan to try any of the 1-8 DAR’s. As outlined above, a DAR value affects the efficacy of the drug, as low drug loading reduces the potency, while high drug loading can negatively affect pharmacokinetics (PK)1 and toxicity. Here, a skilled chemist at the time would simply make the known ADC’s of the known 8 DAR’s. Indeed, it would have been part and parcel to make the different DAR’s to find one that is pharmaceutically acceptable.
With regard to any unpredictability associated with the DAR’s, the notion that unpredictability confers patentability in cases of DAR’s of known ADC’s should be disregarded since a rule of law equating unpredictability to patentability, applied in this case, would mean that any new ADC based on a different DAR would be separately patentable, simply because the formation and properties of each ADC must be verified through testing. This cannot be the proper standard since the expectation of success need only be reasonable, not absolute.
Here, the references provide the reasonable expectation of success, as outlined above. Namely, the references demonstrate the reasonable expectation of success since the references sufficiently characterize the instant ADC’s including the required heavy and light chains, i.e. (SEQ ID NO’s), conjugated to MMAE via a val/cit linker. Again, the expectation of success need only be reasonable, as it is here, and not absolute, (“obviousness does not require absolute predictability, only a reasonable expectation of success, i.e., a reasonable expectation of obtaining similar properties. See, e.g., In re O’Farrell, 853 F.2d 894, 903, 7 USPQ2d 1673, 1681 (Fed. Cir. 1988).”).
Therefore, the rejection is maintained.
Applicant argues that Cui is a non-patent publication that only calls out the compound “cirmtuzumab vedotin” by name and does not provide any information as to the structure of the drug/linker moiety or any information with which to identify the antibody other than to say that it is also called “UC961.” “Cirmtuzumab vedotin” cannot be the same antibody-drug conjugate (ADC) that is in instant claim 1 because Cui states that cirmtuzumab vedotin had a drug-antibody ratio (DAR) of 2.5, while the instant application shows that that ADC depicted in claim 1 (called “ADC-A”) has a measured DAR of from 3.89 to 6. Thus, Cui does not disclose ADC-A.
However, DAR of from 3.89 to 6 is not required by claim 1 and arguments in this regard are not given weight. Nonetheless, DAR are prima facie obvious, as outlined above.
The claims have been amended to recite that the hematological cancer patient has been previously treated for said hematological cancer. However, those ordinary skill would be motivated to try multiple therapies, including the recited ADC, in view of a poor prognosis of cancer.
Claims 1-9, 12, 14, 15 and 19 remain rejected under 35 U.S.C. 103 as being unpatentable over WO 2018237335 (WO 335).
WO 335 describes in example 1 (paragraph [0157]) an immunoconjugate ADC-A resulting from the conjugation of Ab1 with MC-VC-PAB-MMAE, the average DAR being 3.89-5.09. According to Table 1, Ab1 contains SEQ ID NO:3 (which corresponds to SEQ ID NO: 1 of the present application) as the heavy chain (HC) and SEQ ID NO:4 (which corresponds to SEQ ID NO: 2 of the present application) as the light chain (LC). MC-VC-PAB-MMAE is shown in Figure 1 to be similar to the claimed drug moiety of formula (I). In example 8 (paragraphs [0184]-[0196] it is described that ADC-A was administered intravenously in doses of 1, 2 (and 5) mg/kg for the treatment of various cancers (T-cell leukemia, MCL (mantle cell lymphoma), germinal center B-cell like diffuse large B cell lymphoma, Richter's syndrome, human triple negative breast cancer etc (i.e. hematological cancers, solid tumors). It is mentioned that the tumor was completely eradicated (paragraph [0194]). The embodiment of previously treated cancer that has relapsed is described at paragraph [0204].
WO 335 also discloses in example 8 (paragraphs [0184]-[0196]) a weekly dose was given for a total of 4 doses, i.e. on days 1, 8, 15 and 22; a q4d dosing regimen (every 4 days) and in table 11 a dosing regimen is proposed for every 2 weeks for 3-5 administrations and every 4 weeks thereafter.
Nonetheless, the amount of the recited conjugate as an effective dose is a result-effective parameter that will affect the pharmacological and pharmacokinetic properties of the final composition. In this manner, the amount of a specific ingredient in a composition is clearly a result-effective parameter that a person of ordinary skill in the art would routinely optimize.
Specifically, it would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve a desired result. For any compound, the therapeutically effective dose can be estimated initially either in cell culture assays or in animal models, usually rats, rabbits, dogs, or pigs. The animal model also can be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans.
Therapeutic efficacy and toxicity, e.g., ED50 (the dose therapeutically effective in 50% of the population) and LD50 (the dose lethal to 50% of the population), can be determined by standard pharmaceutical procedures in cell cultures or experimental animals. The dose ratio of toxic to therapeutic effects is the therapeutic index, and it can be expressed as the ratio, LD50/ED5o. Pharmaceutical compositions which exhibit large therapeutic indices are preferred. The data obtained from cell culture assays and animal studies is used in formulating a range of dosage for human use. The dosage contained in such compositions is preferably within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage varies within this range depending upon the dosage form employed, sensitivity of the patient, and the route of administration. The exact dosage will be determined by the practitioner, in light of factors related to the subject that requires treatment. Dosage and administration are adjusted to provide sufficient levels of the active ingredient or to maintain the desired effect. Factors which can be taken into account include the severity of the disease state, general health of the subject, age, weight, and gender of the subject, diet, time and frequency of administration, drug combination(s), reaction sensitivities, and tolerance/response to therapy. Long-acting pharmaceutical compositions can be administered once or twice daily every 3 to 4 days, every week, or once every two weeks depending on the half-life and clearance rate of the particular formulation.
Normal dosage amounts can vary from micrograms to 100,000 micrograms, up to a maximum total dose, depending upon the route of administration. Guidance as to particular dosages and methods of delivery is provided in the literature and generally available to practitioners in the art.
In this way, optimization of these parameters is a routine practice, and consequently, would be prima facie obvious, absent factual evidence demonstrating an unexpected benefit of the claimed amount(s).
Those of ordinary skill would have a reasonable expectation that the conjugate can treat the recited cancer since ROR1 is expressed on human malignancies.
Any observed pharmacological effects (see claim 15 and 16 i.e., eradication) would have been a necessary aspect of the conjugates, see MPEP 2112.01 (“Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”).
Again, Applicant argues that the instant ADC is just one disclosed in WO 335 and unexpected benefits.
Again, in example 1 (paragraph [0157]) WO 335 exemplifies ADC-A resulting from the conjugation of Ab1 with MC-VC-PAB-MMAE. Therefore, the reference teaches the instant ADC with the requisite particularity, guidance and reasonable expectation of success.
Any alleged unexpected benefits would have been a necessary aspect of the ADC-A of WO 335.
The claims have been amended to recite that the hematological cancer patient has been previously treated for said hematological cancer. However, those ordinary skill would be motivated to try multiple therapies, including the recited ADC, in view of a poor prognosis of cancer.
Therefore, the rejection is maintained.
Claims 1-9, 12, 14, 15 and 19 remain rejected under 35 U.S.C. 103 as being unpatentable over U.S. Publication No. 20200030454 based on an application by Lannutti et al. (Lannutti).
Lannutti teaches the recited conjugates:
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Lannutti also teaches the instant ant-ROR1 antibody:
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wherein Heavy Chain SEQ ID NO: 3 and Light Chain SEQ ID NO: 4 correspond to the instant Heavy and Light Chains SEQ ID NOS: 1 and 2, respectively
Lannutti may not explicitly teach the instant effective amounts and regimens. Nonetheless, the amount of the recited conjugate as an effective dose is a result-effective parameter that will affect the pharmacological and pharmacokinetic properties of the final composition. In this manner, the amount of a specific ingredient in a composition is clearly a result-effective parameter that a person of ordinary skill in the art would routinely optimize.
Specifically, it would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve a desired result. For any compound, the therapeutically effective dose can be estimated initially either in cell culture assays or in animal models, usually rats, rabbits, dogs, or pigs. The animal model also can be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans.
Therapeutic efficacy and toxicity, e.g., ED50 (the dose therapeutically effective in 50% of the population) and LD50 (the dose lethal to 50% of the population), can be determined by standard pharmaceutical procedures in cell cultures or experimental animals. The dose ratio of toxic to therapeutic effects is the therapeutic index, and it can be expressed as the ratio, LD50/ED5o. Pharmaceutical compositions which exhibit large therapeutic indices are preferred. The data obtained from cell culture assays and animal studies is used in formulating a range of dosage for human use. The dosage contained in such compositions is preferably within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage varies within this range depending upon the dosage form employed, sensitivity of the patient, and the route of administration. The exact dosage will be determined by the practitioner, in light of factors related to the subject that requires treatment. Dosage and administration are adjusted to provide sufficient levels of the active ingredient or to maintain the desired effect. Factors which can be taken into account include the severity of the disease state, general health of the subject, age, weight, and gender of the subject, diet, time and frequency of administration, drug combination(s), reaction sensitivities, and tolerance/response to therapy. Long-acting pharmaceutical compositions can be administered once or twice daily every 3 to 4 days, every week, or once every two weeks depending on the half-life and clearance rate of the particular formulation.
Normal dosage amounts can vary from micrograms to 100,000 micrograms, up to a maximum total dose, depending upon the route of administration. Guidance as to particular dosages and methods of delivery is provided in the literature and generally available to practitioners in the art.
In this way, optimization of these parameters is a routine practice, and consequently, would be prima facie obvious, absent factual evidence demonstrating an unexpected benefit of the claimed amount(s).
Those of ordinary skill would have a reasonable expectation that the conjugate can treat the recited cancer since ROR1 is expressed on human malignancies.
Any observed pharmacological effects (see claim 15 and 16 i.e., eradication) would have been a necessary aspect of the conjugates, see MPEP 2112.01 (“Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”).
Lannutti is in the same family as WO 335, and therefore, the arguments against patentability set for above for WO 335 are appliable here. Therefore, the rejection is maintained.
The claims have been amended to recite that the hematological cancer patient has been previously treated for said hematological cancer. However, those ordinary skill would be motivated to try multiple therapies, including the recited ADC, in view of a poor prognosis of cancer.
Claims 1-9, 12, 14, 15 and 19 remain rejected under 35 U.S.C. 103 as being unpatentable over U.S. Publication No. 20220133901 based on an application by Lannutti et al. (Lannutti II).
Lannutti II teaches the recited conjugates:
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Lannutti II also teaches the instant ant-ROR1 antibody:
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wherein Heavy Chain SEQ ID NO: 3 and Light Chain SEQ ID NO: 4 correspond to the instant Heavy and Light Chains SEQ ID NOS: 1 and 2, respectively
Lannutti II may not explicitly teach the instant effective amounts and regimens. Nonetheless, the amount of the recited conjugate as an effective dose is a result-effective parameter that will affect the pharmacological and pharmacokinetic properties of the final composition. In this manner, the amount of a specific ingredient in a composition is clearly a result-effective parameter that a person of ordinary skill in the art would routinely optimize.
Specifically, it would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve a desired result. For any compound, the therapeutically effective dose can be estimated initially either in cell culture assays or in animal models, usually rats, rabbits, dogs, or pigs. The animal model also can be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans.
Therapeutic efficacy and toxicity, e.g., ED50 (the dose therapeutically effective in 50% of the population) and LD50 (the dose lethal to 50% of the population), can be determined by standard pharmaceutical procedures in cell cultures or experimental animals. The dose ratio of toxic to therapeutic effects is the therapeutic index, and it can be expressed as the ratio, LD50/ED5o. Pharmaceutical compositions which exhibit large therapeutic indices are preferred. The data obtained from cell culture assays and animal studies is used in formulating a range of dosage for human use. The dosage contained in such compositions is preferably within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage varies within this range depending upon the dosage form employed, sensitivity of the patient, and the route of administration. The exact dosage will be determined by the practitioner, in light of factors related to the subject that requires treatment. Dosage and administration are adjusted to provide sufficient levels of the active ingredient or to maintain the desired effect. Factors which can be taken into account include the severity of the disease state, general health of the subject, age, weight, and gender of the subject, diet, time and frequency of administration, drug combination(s), reaction sensitivities, and tolerance/response to therapy. Long-acting pharmaceutical compositions can be administered once or twice daily every 3 to 4 days, every week, or once every two weeks depending on the half-life and clearance rate of the particular formulation.
Normal dosage amounts can vary from micrograms to 100,000 micrograms, up to a maximum total dose, depending upon the route of administration. Guidance as to particular dosages and methods of delivery is provided in the literature and generally available to practitioners in the art.
In this way, optimization of these parameters is a routine practice, and consequently, would be prima facie obvious, absent factual evidence demonstrating an unexpected benefit of the claimed amount(s).
Those of ordinary skill would have a reasonable expectation that the conjugate can treat the recited cancer since ROR1 is expressed on human malignancies.
Any observed pharmacological effects (see claim 15 and 16 i.e., eradication) would have been a necessary aspect of the conjugates, see MPEP 2112.01 (“Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”).
Lannutti II is in the same family as WO 335 and Lannutti, and therefore, the arguments against patentability set for above for WO 335 and Lannutti are appliable here. Therefore, the rejection is maintained.
The claims have been amended to recite that the hematological cancer patient has been previously treated for said hematological cancer. However, those ordinary skill would be motivated to try multiple therapies, including the recited ADC, in view of a poor prognosis of cancer.
The rejection under obvious double patenting is maintained:
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 1-9, 12, 14, 15 and 19 remain rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5, 8-12, 36-40, 43-47, 64-68 of U.S. Patent No. 10335496.
Although the claims at issue are not identical, they are not patentably distinct from each other. Specifically, the conflicting claims anticipate the rejected claims.
In particular, SEQ ID NOS; 5 and 6 correspond to VH and VL chains of the instant Heavy and Light chains of SEQ ID Nos: 1 and 2, respectively. The MC-Val-CIT -PAB-MMAE is also covered by the conflicting claims. In this regard, the difference between the conjugates covered in the rejected claims and those covered in the rejected claims is the conflicting claims may not recite the structure of the instant conjugates with particularity so as to amount to anticipation (See M.P.E.P. § 2131: "[t]he identical invention must be shown in as complete detail as is contained in the ... claim." Richardson v. Suzuki Motor Co., 868 F.2d 1226, 1236, 9 USPQ2d 1913, 1920 (Fed. Cir. 1989). The elements must be arranged as required by the claim, but this is not an ipsissimis verbis test, i.e., identity of terminology is not required. In re Bond, 910 F.2d 831, 15 USPQ2d 1566 (Fed. Cir. 1990).). However, the conflicting claims recite the structural elements of the claimed invention with sufficient guidance, particularity, and with a reasonable expectation of success, that the invention would be prima facie obvious to one of ordinary skill (the prior art reference teaches or suggests all the claim limitations with a reasonable expectation of success. See M.P.E.P. § 2143).
The conflicting claims may not explicitly teach the instant effective amounts and regimens. Nonetheless, the amount of the recited conjugate as an effective dose is a result-effective parameter that will affect the pharmacological and pharmacokinetic properties of the final composition. In this manner, the amount of a specific ingredient in a composition is clearly a result-effective parameter that a person of ordinary skill in the art would routinely optimize.
Specifically, it would have been customary for an artisan of ordinary skill to determine the optimal amount of each ingredient to add in order to best achieve a desired result. For any compound, the therapeutically effective dose can be estimated initially either in cell culture assays or in animal models, usually rats, rabbits, dogs, or pigs. The animal model also can be used to determine the appropriate concentration range and route of administration. Such information can then be used to determine useful doses and routes for administration in humans.
Therapeutic efficacy and toxicity, e.g., ED50 (the dose therapeutically effective in 50% of the population) and LD50 (the dose lethal to 50% of the population), can be determined by standard pharmaceutical procedures in cell cultures or experimental animals. The dose ratio of toxic to therapeutic effects is the therapeutic index, and it can be expressed as the ratio, LD50/ED5o. Pharmaceutical compositions which exhibit large therapeutic indices are preferred. The data obtained from cell culture assays and animal studies is used in formulating a range of dosage for human use. The dosage contained in such compositions is preferably within a range of circulating concentrations that include the ED50 with little or no toxicity. The dosage varies within this range depending upon the dosage form employed, sensitivity of the patient, and the route of administration. The exact dosage will be determined by the practitioner, in light of factors related to the subject that requires treatment. Dosage and administration are adjusted to provide sufficient levels of the active ingredient or to maintain the desired effect. Factors which can be taken into account include the severity of the disease state, general health of the subject, age, weight, and gender of the subject, diet, time and frequency of administration, drug combination(s), reaction sensitivities, and tolerance/response to therapy. Long-acting pharmaceutical compositions can be administered once or twice daily every 3 to 4 days, every week, or once every two weeks depending on the half-life and clearance rate of the particular formulation.
Normal dosage amounts can vary from micrograms to 100,000 micrograms, up to a maximum total dose, depending upon the route of administration. Guidance as to particular dosages and methods of delivery is provided in the literature and generally available to practitioners in the art.
In this way, optimization of these parameters is a routine practice, and consequently, would be prima facie obvious, absent factual evidence demonstrating an unexpected benefit of the claimed amount(s).
Those of ordinary skill would have a reasonable expectation that the conjugate can treat the recited cancer since ROR1 is expressed on human malignancies.
Any observed pharmacological effects (see claim 15 and 16 i.e., eradication) would have been a necessary aspect of the conjugates, see MPEP 2112.01 (“Products of identical chemical composition can not have mutually exclusive properties.” In re Spada, 911 F.2d 705, 709, 15 USPQ2d 1655, 1658 (Fed. Cir. 1990). A chemical composition and its properties are inseparable. Therefore, if the prior art teaches the identical chemical structure, the properties applicant discloses and/or claims are necessarily present. Id.”).
Applicant has not distinguished the claims of the conflicting patent, or any reissue thereof, from the rejected claims. Therefore, the rejection is maintained.
The claims have been amended to recite that the hematological cancer patient has been previously treated for said hematological cancer. However, those ordinary skill would be motivated to try multiple therapies, including the recited ADC, in view of a poor prognosis of cancer.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to KARL J PUTTLITZ whose telephone number is (571)272-0645. The examiner can normally be reached on Monday to Friday from 9 a.m. to 5 p.m.
If attempts to reach the examiner by telephone are unsuccessful, the examiner's acting supervisor, Janet Epps-Smith, can be reached at telephone number (571)272-0757. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/KARL J PUTTLITZ/ Primary Examiner, Art Unit 1646