DETAILED ACTION
The present application is being examined under the pre-AIA first to invent provisions.
Claims 1-19 are pending in the instant application.
Applicant’s election of the diabetes autoantigen species of “preproinsulin” in the reply filed on September 26, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 1-19 are under examination in this office action.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claim 18 is rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
In claim 18, applicant has recited that the administration methods of claim 1 are capable of “preventing the onset of diabetes”. Such an administration is highly problematic. First, while is possible to experimentally induce diabetes in animal models (such as NOD mice) such that artisans know who will and who will not develop diabetes, humans are not amenable to such foreknowledge with patients being diagnosed as having diabetes only once clinical signs and symptoms of the disease are manifest. Obviously if the patient is already showing signs of the disease it can no longer be “prevented” and the instant application does not appear to provide any new diagnostic assay to determine who will or will not develop diabetes in in the future. Further, in working example 4 which did use a mouse model of diabetes the administration of abatacept in combination with a B-chain vaccine was unable to prevent disease, even though it did slow the progress of disease as compared to controls. Thus, while the instant claimed methods might be able to inhibit the onset of diabetes as compared to doing nothing, it does not appear reasonable that the instant claimed methods are capable of the full breadth of “preventing” disease as presently recited.
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.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 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) the invention was known or used by others in this country, or patented or described in a printed publication in this or a foreign country, before the invention thereof by the applicant for a patent.
(b) the invention was patented or described in a printed publication in this or a foreign country or in public use or on sale in this country, more than one year prior to the date of application for patent in the United States.
(e) the invention was described in (1) an application for patent, published under section 122(b), by another filed in the United States before the invention by the applicant for patent or (2) a patent granted on an application for patent by another filed in the United States before the invention by the applicant for patent, except that an international application filed under the treaty defined in section 351(a) shall have the effects for purposes of this subsection of an application filed in the United States only if the international application designated the United States and was published under Article 21(2) of such treaty in the English language.
Claims 1 and 3-7 are rejected under pre-AIA 35 U.S.C. 102(a) as being anticipated by Marketwired as evidenced by Chatenoud et al. disclose that Abatacept (CTLA4-Ig),.
Marketwired discloses that administration of abatacept, a CTLA4-Ig fusion protein, in combination with diabetes autoantigens, provided evidence of clinical efficacy by strengthening immune regulation in a disease-specific manner (see entire document, most particularly the fourth paragraph). Specifically it is disclosed that the diabetes autoantigen used in combination with abatacept is insulin B chain. Note that as evidenced by Chatenoud et al., abatacept is a fusion protein comprising the extracellular domain of CTLA4 fused to an immunoglobulin Fc domain and that CD80/86 are ligands for abatacept (see particularly the section titled CTLA4-Ig beginning on page 6 of Chatenoud et al.). It should also be apparent that insulin B chain is an immunologically active fragment of the longer preproinsulin sequence.
Claim Rejections - 35 USC § 103
The following is a quotation of pre-AIA 35 U.S.C. 103(a) which forms the basis for all obviousness rejections set forth in this Office action:
(a) A patent may not be obtained though the invention is not identically disclosed or described as set forth in section 102 of this title, if the differences between the subject matter sought to be patented and the prior art are such that the subject matter as a whole would have been obvious at the time the invention was made to a person having ordinary skill in the art to which said subject matter pertains. Patentability shall not be negatived by the manner in which the invention was made.
Claims 1-15 and 17-19 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Cohen et al. (US Patent 8,497,247) in view of US 2003/0045467.
Cohen et al. disclose the administration of CTLA4-Ig for the treatment of diabetes mellitus (see entire document, particularly the abstract and claims). The amount of CTLA4-Ig which is to be administered is disclosed in both an individualized basis in mg/kg as well as incremental dosing such as 500 mg for a subject weighing less than 60 kg, 750 mg for a subject weighing 60-100 kg, and 1000 mg for subjects over 100kg (see particularly columns 19 and 20 and columns 31-33) and note that such doses anticipate that presently recited in instant claim 30. Such administrations are disclosed as occurring via numerous routes including intravenous, intramuscular, and subcutaneously either alone or in combination with additional therapeutic agents (see particularly column 39). The use of carriers in pharmaceutical compositions, including oil-based, are disclosed by Cohen et al. (see particularly column 34). It should be noted that the '247 patent to Cohen et al. claims continuity to applications disclosed by paragraph [0029] of the instant specification as disclosing abatacept and thus based upon the evidence presently of record the CTLA4-Ig of Cohen et al. is abatacept. Notably, applicant did not traverse such a finding in great grandparent application 14/253,432 or any subsequent child application. Administration of CTLA4-Ig in combination with additional therapeutic agents is disclosed (see column 40 for example) but these teachings differ from the instant claimed invention in that administration of a diabetes autoantigen, such as preproinsulin, in combination with CTLA4-Ig is not disclosed.
The ‘467 document discloses pharmaceutical compositions which contain preproinsulin in combination with an oil-based adjuvant for the treatment of diabetes, with IFA and Montanide ISA beings specifically taught as oil-based adjuvants (see entire document, particularly paragraphs [0005], [0006], [0009], [0026], [0039-0041], [0117], and claims 1-30, most particularly claims 2, 3, and 9). It should be noted that Montanide ISA contains mannide oleate (see for example paragraphs [0113] and [0163]). The ratio of autoantigen to adjuvant in such composition are disclosed as being 50/50 by weight (see for example paragraphs [0069] and [0089]). Such compositions are disclosed as being administered via multiple routes including parenterally, subcutaneously, intramuscularly, and mucosally (see for example paragraphs [0184-0185]). Additionally, fragments of insulin comprising residues 33-47 or SEQ ID NO:1 are explicitly disclosed as preferred embodiments for autoantigens present in such pharmaceutical compositions (see most particularly paragraph [0027]).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the invention was filed to combine CTLA4-Ig in a composition with the diabetes autoantigen preproinsulin, based on the teachings of Cohen that CTLA4-Ig can be used to treat diabetes and combined with other agents known to treat the autoimmune disease, and the teachings of the ‘467 document that preproinsulin is to be administered in conjunction with oil based adjuvants including IFA for the treatment of diabetes. Applicant is reminded that "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose .... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06.
It is noted that ‘467 document does not appear to disclose specific doses for preproinsulin which are administered to treat diabetes. However, optimizing the dose of a therapeutic agent to best treat a disease is a routine and common practice for artisans as is acknowledged by the ‘467 document (see particularly paragraph [0186]) and thus determining how much autoantigen to combine with the CTLA4-Ig of Cohen et al. is a matter of optimizing a results effective variable, with the “variable” being the dose and the “result” being patient treatment/outcome. It should be pointed out that the courts have long ruled that “[W]here the general conditions of a claim 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, 105 USPQ 233, 235 (CCPA 1955). Given that the amount of drug in a dose is correlated with efficacy of disease treatment as discussed above, finding a suitable dose for administration is prima facie obvious in the absence of evidence to the contrary.
Claims 1-15 and 17-19 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Marketwired in view of Cohen et al. (US Patent 8,497,247) and in view of US 2003/0045467.
Marketwired discloses that administration of abatacept, a CTLA4-Ig fusion protein, in combination with diabetes autoantigens, provided evidence of clinical efficacy by strengthening immune regulation in a disease-specific manner (see entire document, most particularly the fourth paragraph). These teachings differ from the instant claimed invention in that the diabetes autoantigen is insulin B chain rather than preproinsulin and specific masses for active ingredients and adjuvants are not disclosed.
Cohen et al. disclose the administration of CTLA4-Ig for the treatment of diabetes mellitus (see entire document, particularly the abstract and claims). The amount of CTLA4-Ig which is to be administered is disclosed in both an individualized basis in mg/kg as well as incremental dosing such as 500 mg for a subject weighing less than 60 kg, 750 mg for a subject weighing 60-100 kg, and 1000 mg for subjects over 100kg (see particularly columns 19 and 20 and columns 31-33) and note that such doses anticipate that presently recited in instant claim 30. Such administrations are disclosed as occurring via numerous routes including intravenous, intramuscular, and subcutaneously either alone or in combination with additional therapeutic agents (see particularly column 39). The use of carriers in pharmaceutical compositions, including oil-based, are disclosed by Cohen et al. (see particularly column 34). Administration of CTLA4-Ig in combination with additional therapeutic agents is also disclosed (see column 40 for example) and based upon the evidence of record the CTLA4-Ig fusion protein used by Cohen et al. appears to be abatacept.
The ‘467 document discloses pharmaceutical compositions which contain preproinsulin in combination with an oil-based adjuvant for the treatment of diabetes, with IFA and Montanide ISA beings specifically taught as oil-based adjuvants (see entire document, particularly paragraphs [0005], [0006], [0009], [0026], [0039-0041], [0117], and claims 1-30, most particularly claims 2, 3, and 9). It should be noted that Montanide ISA contains mannide oleate (see for example paragraphs [0113] and [0163]). The ratio of autoantigen to adjuvant in such composition are disclosed as being 50/50 by weight (see for example paragraphs [0069] and [0089]). Such compositions are disclosed as being administered via multiple routes including parenterally, subcutaneously, intramuscularly, and mucosally (see for example paragraphs [0184-0185]). Additionally, fragments of insulin comprising residues 33-47 or SEQ ID NO:1 are explicitly disclosed as preferred embodiments for autoantigens present in such pharmaceutical compositions, and it should be readily apparent that any insulin is a fragment of the preproinsulin precursor polypeptide (see most particularly paragraph [0027]).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the invention was filed to modify the teachings of the Marketwired reference to arrive at the claimed invention. Specifically, artisans would know that abatacept successfully treats autoimmune diabetes as evidenced by both the Marketwired document and Cohen et al., with increased efficacy being expected by combining abatacept with diabetes autoantigens as is taught by the Marketwired reference. Thus it would have been obvious to an ordinary artisan that full length preproinsulin could be substituted for the insulin B-chain used in the as they are related (specifically B chain is a fragment of preproinsulin) and both are taught for use in vaccines to treat diabetes. Applicant is reminded that "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose .... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06.
It is noted that ‘467 document does not appear to disclose specific doses for preproinsulin which are administered to treat diabetes. However, optimizing the dose of a therapeutic agent to best treat a disease is a routine and common practice for artisans as is acknowledged by the ‘467 document (see particularly paragraph [0186]) and thus determining how much autoantigen to combine with abatacept is a matter of optimizing a results effective variable, with the “variable” being the dose and the “result” being patient treatment/outcome. It should be pointed out that the courts have long ruled that “[W]here the general conditions of a claim 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, 105 USPQ 233, 235 (CCPA 1955). Given that the amount of drug in a dose is correlated with efficacy of disease treatment as discussed above, finding a suitable dose for administration is prima facie obvious in the absence of evidence to the contrary.
Claims 1-15 and 17-19 are rejected under pre-AIA 35 U.S.C. 103(a) as being obvious over Chatenoud et al. in view of US 2003/0045467.
Chatenoud et al. disclose that Abatacept (CTLA4-Ig), insulin and its fragments, GAD 65 and a fragment of HSP60 all have been used in clinical trials for the treatment of diabetes mellitus (see entire document, particularly the abstract and pages 6 and 12-13). Administration of CTLA4-Ig is disclosed as They disclose that the best way to treat diabetes "is, of course, to address combination strategies. As for all complex diseases in T1 D [type 1 diabetes], it is obvious that only by combining agents, one may take advantage of synergies in the mode of action, reduce the dosages of single drugs, thereby decreasing side effects." (see page 14, most particularly the bottom of the left column). With regard to administration of autoantigens, Chatenoud et al. disclose that "One promising development in the field of antigen-based therapies was the combination of antigen with adjuvant for vaccination." (see particularly the left column of page 13) and that administration of autoantigen in the correct context is thought to work by expanding the number and/or function of regulatory T cells (see particularly the paragraph spanning pages 2 and 3). Such teachings differ from the instant claimed invention that the use of preproinsulin as a diabetes autoantigen is not disclosed.
The ‘467 document discloses pharmaceutical compositions which contain preproinsulin in combination with an oil-based adjuvant for the treatment of diabetes, with IFA and Montanide ISA beings specifically taught as oil-based adjuvants (see entire document, particularly paragraphs [0005], [0006], [0009], [0026], [0039-0041], [0117], and claims 1-30, most particularly claims 2, 3, and 9). It should be noted that Montanide ISA contains mannide oleate (see for example paragraphs [0113] and [0163]). The ratio of autoantigen to adjuvant in such composition are disclosed as being 50/50 by weight (see for example paragraphs [0069] and [0089]). Such compositions are disclosed as being administered via multiple routes including parenterally, subcutaneously, intramuscularly, and mucosally (see for example paragraphs [0184-0185]). Additionally, fragments of insulin comprising residues 33-47 or SEQ ID NO:1 are explicitly disclosed as preferred embodiments for autoantigens present in such pharmaceutical compositions (see most particularly paragraph [0027]).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the invention was made to combine CTLA4-Ig in a composition with the Type 1 diabetes autoantigen preproinsulin for use in methods of treating diabetes. The courts have long ruled that "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose .... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06. Further, Chatenoud et al. explicitly teach the desirability of combination therapies to treat diabetes and that such combinations are expected to act synergistically due to different modes of action resulting in smaller doses of drugs and compared to monotherapy and decreased side effects (see particularly the left column of page 14). It is noted that specific dosages, such as those recited in instant claim 27, are not disclosed by Chatenoud et al. or the ‘467 document. However, the reagents disclosed by Chatenoud et al. are disclosed as being useful in treating diabetes and therefore determining how much of a drug to give to achieve this endpoint is a matter of routine optimization for artisans, as is taught in the ‘467 document (see particularly paragraph [0186]). The courts have long ruled that “[W]here the general conditions of a claim 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, 105 USPQ 233, 235 (CCPA 1955). In the instant case, the amount of drug in a dose is a results effective variable wherein the does is the “variable” which is correlated with the “result” of successful treatment of the disease in question, namely diabetes. Thus, determining how much drug to use in a therapeutic dose requires no more than routine optimization and thus is prima facie obvious in the absence of evidence to the contrary.
Claims 1-4, 6-15, and 17-19 are rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Gray et al. (US 2004/0151725) in view of US 2003/0045467.
Gray et al. disclose the construction of CTLA4-Ig fusion proteins and their administration to patients to treat autoimmune diseases (see entire document, particularly the abstract and claims). Compositions containing CTLA4-Ig and pharmaceutically acceptable carriers are disclosed, including oil-based compositions (see particularly paragraphs [0074-0082], most particularly [0078]). It is further disclosed that to treat autoimmune diseases with a known autoantigen, it is desirable to coadminister CTLA4-Ig in combination with said known autoantigen, and that a disease amenable to such administration of such compositions is diabetes mellitus (see particularly paragraph [0095]). Such compositions are administered by a variety of injectable routes including intravenously and subcutaneously (see for example paragraph [0076]). These teachings differ from the instant claimed invention in that preproinsulin is not disclosed as a known autoantigen in the disease diabetes mellitus.
The ‘467 document discloses pharmaceutical compositions which contain preproinsulin in combination with an oil-based adjuvant for the treatment of diabetes, with IFA and Montanide ISA beings specifically taught as oil-based adjuvants (see entire document, particularly paragraphs [0005], [0006], [0009], [0026], [0039-0041], [0117], and claims 1-30, most particularly claims 2, 3, and 9). It should be noted that Montanide ISA contains mannide oleate (see for example paragraphs [0113] and [0163]). The ratio of autoantigen to adjuvant in such composition are disclosed as being 50/50 by weight (see for example paragraphs [0069] and [0089]). Such compositions are disclosed as being administered via multiple routes including parenterally, subcutaneously, intramuscularly, and mucosally (see for example paragraphs [0184-0185]). Additionally, fragments of insulin comprising residues 33-47 or SEQ ID NO:1 are explicitly disclosed as preferred embodiments for autoantigens present in such pharmaceutical compositions (see most particularly paragraph [0027]).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the instant application was filed to have made a composition comprising both CTLA4-Ig and preproinsulin. This is because Gray et al. explicitly teach that their CTLA4-Ig is to be coadministered with a known antigen to treat the autoimmune disease diabetes mellitus and the ‘467 document discloses that preproinsulin is an autoantigen in diabetes. Further, the courts have long ruled that “It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art.” In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980) (citations omitted). In the instant case, both CTLA4-Ig as well as preproinsulin in IFA are taught in the prior art for treating diabetes.
It is noted that Gray et al. do not disclose specific doses for their CTLA4-Ig fusion proteins, but they do teach that it is routine for artisans to determine an effective dose considering variables such as the disease state, age, weight and sex of a patient to optimize the therapeutic response to their administered fusion protein (see particularly paragraph [0075]). As such, figuring out how much CTLA4-Ig to place into a therapeutic composition is a results effective variable as artisans will optimize how much drug to put into the composition so that the patient’s disease, in this case diabetes, is effectively treated. Similarly, the ‘467 document also discloses that dosing is subject to routine optimization by artisans (see particularly paragraph [0186]). It should also be pointed out that the courts have long ruled that “[W]here the general conditions of a claim 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, 105 USPQ 233, 235 (CCPA 1955). Given that the amount of drug in a dose is correlated with efficacy of disease treatment as discussed above, finding a suitable dose for administration is prima facie obvious in the absence of evidence to the contrary.
Claim 5 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Gray et al. (US 2004/0151725) in view of US 2003/0045467 as applied to claims 1-4, 6-15, and 17-19 above, and further in view of Chatenoud et al.
The inventions rendered obvious by the teachings of Gray et al. and the '467 document have been discussed above and differ from the instant claimed invention in that the CTLA4-Ig constructs of Gray et al are not taught as being abatacept.
Chatenoud et al. disclose that Abatacept (CTLA4-Ig) has been used in clinical trials for the treatment of diabetes mellitus (see entire document, particularly the abstract and page 6). It is also disclosed that the best way to treat diabetes "is, of course, to address combination strategies. As for all complex diseases in T1 D it is obvious that only by combining agents, one may take advantage of synergies in the mode of action, reduce the dosages of single drugs, thereby decreasing side effects." (see page 14, most particularly the bottom of the left column).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the instant invention was made to substitute abatacept for the CTLA4-Ig used in the compositions and methods of administration rendered obvious by the teachings of Gray et al. and the ‘467 document since abatacept has the advantage of being successfully used in human therapy as taught by Chatenoud et al.
Claim 16 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Cohen et al. (US Patent 8,497,247) in view of US 2003/0045467 as applied to claims 1-15 and 17-19 above, and further in view of Orban et al.
The inventions rendered obvious by the collective teachings of the prior art have been discussed above and differ from that which is presently claimed in that measuring the level of insulin C peptide in blood is not taught as a marker for monitoring disease progression.
Orban et al. disclose that measuring the level of C peptide in patient blood can be used to monitor the course of disease progression in diabetes patients (see entire document, particularly the abstract, section 2.3 titled Study Design, Figure 1, and the discussion section). It should be noted that C peptide is a fragment or preproinsulin, and that the amount of C peptide is a proxy for the amount of insulin being produced by the patient.
Therefore it would have been obvious to artisans to include a step of monitoring disease progression by measuring C peptide in blood samples as such assays are routinely done for diabetic patients. Performing such assays would provide artisans with information as to how the patient was responding to the treatment methods rendered obvious by the teachings of the prior art.
Claim 16 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Marketwired in view of Cohen et al. (US Patent 8,497,247) and in view of US 2003/0045467 as applied to claims 1-15 and 17-19 above, and further in view of Orban et al.
The inventions rendered obvious by the collective teachings of the prior art have been discussed above and differ from that which is presently claimed in that measuring the level of insulin C peptide in blood is not taught as a marker for monitoring disease progression.
Orban et al. disclose that measuring the level of C peptide in patient blood can be used to monitor the course of disease progression in diabetes patients (see entire document, particularly the abstract, section 2.3 titled Study Design, Figure 1, and the discussion section). It should be noted that C peptide is a fragment or preproinsulin, and that the amount of C peptide is a proxy for the amount of insulin being produced by the patient.
Therefore it would have been obvious to artisans to include a step of monitoring disease progression by measuring C peptide in blood samples as such assays are routinely done for diabetic patients. Performing such assays would provide artisans with information as to how the patient was responding to the treatment methods rendered obvious by the teachings of the prior art.
Claim 16 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Chatenoud et al. in view of US 2003/0045467 as applied to claims 1-15 and 17-19 above, and further in view of Orban et al.
The inventions rendered obvious by the collective teachings of the prior art have been discussed above and differ from that which is presently claimed in that measuring the level of insulin C peptide in blood is not taught as a marker for monitoring disease progression.
Orban et al. disclose that measuring the level of C peptide in patient blood can be used to monitor the course of disease progression in diabetes patients (see entire document, particularly the abstract, section 2.3 titled Study Design, Figure 1, and the discussion section). It should be noted that C peptide is a fragment or preproinsulin, and that the amount of C peptide is a proxy for the amount of insulin being produced by the patient.
Therefore it would have been obvious to artisans to include a step of monitoring disease progression by measuring C peptide in blood samples as such assays are routinely done for diabetic patients. Performing such assays would provide artisans with information as to how the patient was responding to the treatment methods rendered obvious by the teachings of the prior art.
Claim 16 is rejected under pre-AIA 35 U.S.C. 103(a) as being unpatentable over Gray et al. (US 2004/0151725) in view of US 2003/0045467 as applied to claims 1-4, 6-15 and 17-19 above, and further in view of Orban et al.
The inventions rendered obvious by the collective teachings of the prior art have been discussed above and differ from that which is presently claimed in that measuring the level of insulin C peptide in blood is not taught as a marker for monitoring disease progression.
Orban et al. disclose that measuring the level of C peptide in patient blood can be used to monitor the course of disease progression in diabetes patients (see entire document, particularly the abstract, section 2.3 titled Study Design, Figure 1, and the discussion section). It should be noted that C peptide is a fragment or preproinsulin, and that the amount of C peptide is a proxy for the amount of insulin being produced by the patient.
Therefore it would have been obvious to artisans to include a step of monitoring disease progression by measuring C peptide in blood samples as such assays are routinely done for diabetic patients. Performing such assays would provide artisans with information as to how the patient was responding to the treatment methods rendered obvious by the teachings of the prior art.
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 claims at issue 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); and 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/forms/. The 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1 and 3-12 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 8,735,359. Although the claims at issue are not identical, they are not patentably distinct from each other because the issued clams anticipate that which is presently claimed.
Specifically, the application which gave rise to the ‘359 patent is the great-great-grandparent of the instant application. The issued claims recite methods of treating diabetes by administering preproinsulin and a CTLA4 fusion protein to a subject (see all issued claims, particularly issued claim 1). Notably the CTLA4 fusion protein is recited as being abatacept (issued claim 2), and the drugs are recited as being present in the oil-based carriers IFA and Montanide ISA (see issued claim 5). As such the issued claims are narrower in scope than that which is presently claimed.
Claims 2, 13-15, and 17-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 8,735,359 as applied to claims 1 and 3-12 above, and further in view of Cohen et al. (US Patent 8,497,247) and in view of US 2003/0045467.
The inventions anticipated by the claims of the ‘359 patent have been discussed above and differ from the instant claimed inventions in that the issued claims do not explicitly recite routes by which the compositions are administered or the amounts of various ingredients in the administered compositions.
Cohen et al. disclose the administration of CTLA4-Ig for the treatment of diabetes mellitus (see entire document, particularly the abstract and claims). The amount of CTLA4-Ig which is to be administered is disclosed in both an individualized basis in mg/kg as well as incremental dosing such as 500 mg for a subject weighing less than 60 kg, 750 mg for a subject weighing 60-100 kg, and 1000 mg for subjects over 100kg (see particularly columns 19 and 20 and columns 31-33) and note that such doses anticipate that presently recited in instant claim 30. Such administrations are disclosed as occurring via numerous routes including intravenous, intramuscular, and subcutaneously either alone or in combination with additional therapeutic agents (see particularly column 39). The use of carriers in pharmaceutical compositions, including oil-based, are disclosed by Cohen et al. (see particularly column 34). It should be noted that the '247 patent to Cohen et al. claims continuity to applications disclosed by paragraph [0029] of the instant specification as disclosing abatacept and thus based upon the evidence presently of record the CTLA4-Ig of Cohen et al. is abatacept. Administration of CTLA4-Ig in combination with additional therapeutic agents is disclosed (see column 40 for example).
The ‘467 document discloses pharmaceutical compositions which contain preproinsulin in combination with an oil-based adjuvant for the treatment of diabetes, with IFA and Montanide ISA beings specifically taught as oil-based adjuvants (see entire document, particularly paragraphs [0005], [0006], [0009], [0026], [0039-0041], [0117], and claims 1-30, most particularly claims 2, 3, and 9). It should be noted that Montanide ISA contains mannide oleate (see for example paragraphs [0113] and [0163]). The ratio of autoantigen to adjuvant in such composition are disclosed as being 50/50 by weight (see for example paragraphs [0069] and [0089]). Such compositions are disclosed as being administered via multiple routes including parenterally, subcutaneously, intramuscularly, and mucosally (see for example paragraphs [0184-0185]).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the invention was filed to practice the issued ‘359 patent administration methods wherein the abatacept and preproinsulin are in either in the same or separate compositions at staggered or simultaneous times. Issued claim 1 recites that administering both active ingredients in a pharmaceutically acceptable carrier and logically there are only two options, namely administering the reagents separately or in the same composition. Further, it both active ingredients are present in the same composition it is impossible to administer them in any manner other than simultaneous. Separate compositions realistically are usually sequential although theoretically they can be administered simultaneously if two people are doing the administration, for example the first person administers the abatacept syringe while the second administers the preproinsulin syringe with both administrations taking place on the count of three. Even in the absence of such common sense, Cohen et al. teach that CTLA4-Ig is to be used to treat diabetes and combined with other agents known to treat the autoimmune disease, while the teachings of the ‘467 document disclose that preproinsulin is to be administered in conjunction with oil based adjuvants including IFA for the treatment of diabetes. Applicant is reminded that "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose .... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06.
It is noted that neither the issued claims nor the ‘467 document appear to disclose specific doses for preproinsulin which are administered to treat diabetes. However, optimizing the dose as well as the timing of a therapeutic agent to best treat a disease is a routine and common practice for artisans as is acknowledged by the ‘467 document (see particularly paragraph [0186]) and thus determining how much autoantigen to combine with the CTLA4-Ig such as abatacept is a matter of optimizing a results effective variable, with the “variable” being the dose and the “result” being patient treatment/outcome. It should be pointed out that the courts have long ruled that “[W]here the general conditions of a claim 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, 105 USPQ 233, 235 (CCPA 1955). Given that the amount of drug in a dose is correlated with efficacy of disease treatment as discussed above, finding a suitable dose for administration is prima facie obvious in the absence of evidence to the contrary.
Claim 16 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. 8,735,359 as applied to claims 1 and 3-12 above, and further in view of Orban et al.
The inventions of the patented claims have been discussed above and differ from that which is presently claimed in that measuring the level of insulin C peptide in blood is not taught as a marker for monitoring disease progression.
Orban et al. disclose that measuring the level of C peptide in patient blood can be used to monitor the course of disease progression in diabetes patients (see entire document, particularly the abstract, section 2.3 titled Study Design, Figure 1, and the discussion section). It should be noted that C peptide is a fragment or preproinsulin, and that the amount of C peptide is a proxy for the amount of insulin being produced by the patient.
Therefore it would have been obvious to artisans to include a step of monitoring disease progression by measuring C peptide in blood samples as such assays are routinely done for diabetic patients when performing the methods of the issued patent. Performing such assays would provide artisans with information as to how the patient was responding to the treatment methods of the issued claims.
Claims 1-15 and 17-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10,233,242 in view of Cohen et al. (US Patent 8,497,247) and in view of US 2003/0045467.
The issued claims of the ‘242 patent recite methods of treating diabetes by administering a composition comprising CTLA4 fusion proteins including abatacept present in water-in-oil compositions (see all issued claims, particularly 1 and 2). Such compositions are recited as being administered intravenously as well as at various masses of drug. The issued claims differ from what is presently claimed in that the issued claims do not recite administration of preproinsulin.
Cohen et al. disclose the administration of CTLA4-Ig for the treatment of diabetes mellitus (see entire document, particularly the abstract and claims). The amount of CTLA4-Ig which is to be administered is disclosed in both an individualized basis in mg/kg as well as incremental dosing such as 500 mg for a subject weighing less than 60 kg, 750 mg for a subject weighing 60-100 kg, and 1000 mg for subjects over 100kg (see particularly columns 19 and 20 and columns 31-33) and note that such doses anticipate that presently recited in instant claim 30. Such administrations are disclosed as occurring via numerous routes including intravenous, intramuscular, and subcutaneously either alone or in combination with additional therapeutic agents (see particularly column 39). The use of carriers in pharmaceutical compositions, including oil-based, are disclosed by Cohen et al. (see particularly column 34).
The ‘467 document discloses pharmaceutical compositions which contain preproinsulin in combination with an oil-based adjuvant for the treatment of diabetes, with IFA and Montanide ISA beings specifically taught as oil-based adjuvants (see entire document, particularly paragraphs [0005], [0006], [0009], [0026], [0039-0041], [0117], and claims 1-30, most particularly claims 2, 3, and 9). It should be noted that Montanide ISA contains mannide oleate (see for example paragraphs [0113] and [0163]). The ratio of autoantigen to adjuvant in such composition are disclosed as being 50/50 by weight (see for example paragraphs [0069] and [0089]). Such compositions are disclosed as being administered via multiple routes including parenterally, subcutaneously, intramuscularly, and mucosally (see for example paragraphs [0184-0185]).
Therefore, it would have been obvious to a person of ordinary skill in the art at the time the invention was filed to modify the issued ‘242 patent administration methods to include the administration of preproinsulin. This is because Cohen et al. teach that CTLA4-Ig is to be administered to treat diabetes and combined with other agents known to treat the autoimmune disease, and the teachings of the ‘467 document that preproinsulin is to be administered in conjunction with oil based adjuvants including IFA for the treatment of diabetes. Applicant is reminded that "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose .... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980). See MPEP 2144.06.
It should be pointed out that when administering two active therapeutic agents, logically there are only two options, namely administering the reagents separately or in the same composition. Further, it both active ingredients are present in the same composition it is impossible to administer them in any manner other than simultaneous. Separate compositions realistically are usually sequential although theoretically they can be administered simultaneously if two people are doing the administration as was discussed in more depth elsewhere in in this office action, and such information would be well known to ordinary artisans who are medical professionals well versed in the administration of therapeutic agents to best meet the needs of their patients.
It is noted that neither the issued claims nor the ‘467 document appear to disclose specific doses for preproinsulin which are administered to treat diabetes. However, optimizing the dose as well as the timing of a therapeutic agent to best treat a disease is a routine and common practice for artisans as is acknowledged by the ‘467 document (see particularly paragraph [0186]) and thus determining how much autoantigen to combine with the CTLA4-Ig such as abatacept is a matter of optimizing a results effective variable, with the “variable” being the dose and the “result” being patient treatment/outcome. It should be pointed out that the courts have long ruled that “[W]here the general conditions of a claim 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, 105 USPQ 233, 235 (CCPA 1955). Given that the amount of drug in a dose is correlated with efficacy of disease treatment as discussed above, finding a suitable dose for administration is prima facie obvious in the absence of evidence to the contrary.
Claim 16 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 10,233,242 in view of Cohen et al. (US Patent 8,497,247) and in view of US 2003/0045467 as applied to claims 1-15 and 17-19, and further in view of Orban et al.
The obvious variations of the issued claims based upon the teachings of the prior art have been discussed above and differ from that which is presently claimed in that measuring the level of insulin C peptide in blood is not taught as a marker for monitoring disease progression.
Orban et al. disclose that measuring the level of C peptide in patient blood can be used to monitor the course of disease progression in diabetes patients (see entire document, particularly the abstract, section 2.3 titled Study Design, Figure 1, and the discussion section). It should be noted that C peptide is a fragment or preproinsulin, and that the amount of C peptide is a proxy for the amount of insulin being produced by the patient.
Therefore it would have been obvious to artisans to include a step of monitoring disease progression by measuring C peptide in blood samples as such assays are routinely done for diabetic patients when performing the methods rendered obvious by the combination of the ‘242 methods in view of the prior art. The addition of such a step would provide artisans with information as to how the patient was responding to the diabetes treatment methods.
Claims 1-15 and 17-19 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,286,303 in view of Cohen et al. (US Patent 8,497,247) and in view of US 2003/0045467.
The issued claims of the ‘303 patent recite methods of treating diabetes by administer