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 .
Status of the Claims
Claims 1-28 were originally filed May 19, 2022.
The amendment received September 13, 2022 amended claims 1 and 15 and canceled claims 2, 3, 9-14, and 18-28.
The amendment received May 27, 2025 changed the status identifiers only.
The amendment received November 24, 2025 amended claims 1 and 4-6 and canceled claims 7 and 8.
Claims 1, 4-6, and 15-17 are currently pending.
Claims 1 and 4-6 are currently under consideration.
Election/Restrictions
Applicant elected, without traverse, Group I (claims 1 and 4-8) in the reply filed on May 27, 2025.
Claims 15-17 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected method, there being no allowable generic or linking claim.
Applicant elected, without traverse, SEQ ID NO: 3 with I91L, R101A, Q123K, K207A, V343A, and R346V mutations; IgG1 Fc; and capable of inhibiting neutrophil elastase activity as the species in the reply filed on May 27, 2025. 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)).
Potential Rejoinder
Applicant elected claims directed to a product. If a product claim is subsequently found allowable, withdrawn process claims that depend from or otherwise include all the limitations of the allowable product claim will be rejoined in accordance with the provisions of MPEP § 821.04. Process claims that depend from or otherwise include all the limitations of the patentable product will be entered as a matter of right if the amendment is presented prior to final rejection or allowance, whichever is earlier. Amendments submitted after final rejection are governed by 37 CFR 1.116; amendments submitted after allowance are governed by 37 CFR 1.312.
In the event of rejoinder, the requirement for restriction between the product claims and the rejoined process claims will be withdrawn, and the rejoined process claims will be fully examined for patentability in accordance with 37 CFR 1.104. Thus, to be allowable, the rejoined claims must meet all the criteria for patentability including the requirements of 35 U.S.C. 101, 102, 103, and 112. Until an elected product claim is found allowable, an otherwise proper restriction requirement between product claims and process claims may be maintained. Withdrawn process claims that are not commensurate in scope with an allowed product claim will not be rejoined. See “Guidance on Treatment of Product and Process Claims in light of In re Ochiai, In re Brouwer and 35 U.S.C. § 103(b),” 1184 O.G. 86 (March 26, 1996). Additionally, in order to retain the right to rejoinder in accordance with the above policy, applicant is advised that the process claims should be amended during prosecution either to maintain dependency on the product claims or to otherwise include the limitations of the product claims. Failure to do so may result in a loss of the right to a rejoinder. Further, note that the prohibition against double patenting rejections of 35 U.S.C. 121 does not apply where the restriction requirement is withdrawn by the examiner before the patent issues. See MPEP § 804.01.
Sequence Interpretation
The Office interprets claims comprising SEQ ID NOs: in the following manner: “comprising a sequence of SEQ ID NO: 1” requires only a 2mer of SEQ ID NO: 1, “comprising the sequence of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 with any N-/C-terminal additions or any 5’/3’ additions, “consisting of SEQ ID NO: 1” requires the full-length sequence with 100% identity to SEQ ID NO: 1 and the same length as SEQ ID NO: 1, and “selected from the group consisting of SEQ ID NOs: 1, 2, and 3” requires the full-length sequence with 100% identity to SEQ ID NOs: 1, 2, or 3 and the same length as SEQ ID NOs: 1, 2, or 3.
Priority
The present application is a 371 (National Stage) of PCT/US2020/061347 filed November 19, 2020 which claims the benefit of 62/938,859 filed November 21, 2019.
Specification
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Withdrawn Objections
The objection to the disclosure regarding the first line of the specification should be updated to include PCT/US2020/061347 filed November 19, 2020 is withdrawn in view of the amendment received November 24, 2025.
The objection to the disclosure regarding Figure 7C is not described is withdrawn in view of the amendment received November 24, 2025.
The objection to claim 1 regarding “having” should read “comprising” is withdrawn in view of the amendment received November 24, 2025.
The objection to claim 1 regarding “and” should read “and/or” to correlate with “one or more” is withdrawn in view of the amendment received November 24, 2025.
The objection to claim 1 regarding “the variant” should read “the PAI-1 variant” is withdrawn in view of the amendment received November 24, 2025.
The objection to claim 4 regarding “selected from” should read “selected from the group consisting of” is withdrawn in view of the amendment received November 24, 2025.
The objection to claim 5 regarding “Fc domain” should read “Fc domain monomer” is withdrawn in view of the amendment received November 24, 2025.
The objection to claim 5 regarding “has” should read “comprising” (see a)-d)) is withdrawn in view of the amendment received November 24, 2025.
The objection to claim 5 regarding “recited in” should read “of” is withdrawn in view of the amendment received November 24, 2025.
The objection to claim 5 regarding a single conjunction should be utilized (i.e. “or” between a) and b), b) and c) are unnecessary) is withdrawn in view of the amendment received November 24, 2025.
The objection to claim 5 regarding “and” is missing between V343A, R346V (see the last line) is withdrawn in view of the amendment received November 24, 2025.
The objection to claim 6 regarding “has” should read “comprising” (see a)-d)) is withdrawn in view of the amendment received November 24, 2025.
The objection to claim 6 regarding “recited in” should read “of” is withdrawn in view of the amendment received November 24, 2025.
The objection to claim 6 regarding “and” is missing between V343A, R346V (see line 7) is withdrawn in view of the amendment received November 24, 2025.
The objection to claim 7 regarding “and” should read “and/or” to correlate with “one or more” is withdrawn in view of the cancellation of the claim in the amendment received November 24, 2025.
Maintained Objection
Claim 6 is objected to because of the following informalities: “and” is missing between V343A, R346V (see line 5). Appropriate correction is required.
Arguments and Response
Applicants’ arguments directed to the objection for claim 6 were considered but are not persuasive for the following reasons.
Applicants contend that the amendment received November 24, 2025 negates the objection.
Applicants’ arguments are not convincing since “and” was not added to line 5.
New Objection Necessitated by Amendment
Claim Objections
Claim 6 is objected to because of the following informalities: “in” in line 2 should be deleted. Appropriate correction is required.
Withdrawn Rejections
The rejection of claims 1 and 4-8 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of the amendment received November 24, 2025.
The rejection of claims 7 and 8 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of the cancellation of the claims in the amendment received November 24, 2025.
The rejection of claims 7 and 8 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in view of the cancellation of the claims in the amendment received November 24, 2025.
The rejection of claims 7 and 8 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in view of the cancellation of the claims in the amendment received November 24, 2025.
Maintained and/or Modified* Rejections
*wherein the modification is due to amendment
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.
Claim 1 is rejected under 35 U.S.C. 103 as being unpatentable over Lawrence et al. WO 97/39028 published October 23, 1997 and Wu et al., 2014, Pharmacokinetics of Peptide-Fc Fusion Proteins, Journal of Pharmaceutical Sciences, 103: 53-64.
For present claim 1, Lawrence et al. teach human PAI-1 mutants comprising I91L, Q123K, V343A, and/or R346V which inhibit neutrophil elastase activity and vitronectin binding (please refer to the entire specification particularly the abstract; Description; Figures; Examples; claims; pages 1, 2, 4-11, 13-15, 20, 22, 23, 24, 26, 30, 67-71, 89).
However, Lawrence et al. do not teach a Fc fusion.
For present claim 1, Wu et al. teach the benefits of conjugating Fc to polypeptides including extended half-life (please refer to the entire specification particularly the abstract; Introduction; Table 2; Distinct PK Characteristics of Peptibodies).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. addition of Fc extends serum half-life) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. fusing Fc to polypeptides) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” (e.g. making fusion polypeptides with Fc to extend serum half-life). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Lawrence et al. and Wu et al. for claim 1 were considered but are not persuasive for the following reasons.
Applicants contend that the examiner of record relied on references that only teach individual mutations of PAI-1 and not references that teach a combination of mutations as presently claimed. Applicants also contend that since the Fc fusion reference does not teach PAI-1, the reference would not be combined with the PAI-1 reference.
Applicants’ arguments are not convincing since the teachings of Lawrence et al. and Wu et al. render the PAI-1 variant of the instant claims prima facie obvious. Present independent claim 1 requires one or more mutations of I91L, Q123K, V343A and/or R346V. Lawrence et al. teaches single mutations of V343A or R346V and multiple mutations of V343A and/or R346V alone or in combination with I91L and/or Q123K (please refer to the entire specification particularly pages 14, 15, 20, 22, 24, 26, 30; claims).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. addition of Fc extends serum half-life) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. fusing Fc to polypeptides) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” (e.g. making fusion polypeptides with Fc to extend serum half-life). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Claims 1 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Li et al., 2013, Mechanistic characterization and crystal structure of a small molecule inactivator bound to plasminogen activator inhibitor-1, PNAS, E4941-E4949 and Wu et al., 2014, Pharmacokinetics of Peptide-Fc Fusion Proteins, Journal of Pharmaceutical Sciences, 103: 53-64.
For present claims 1 and 4, Li et al. teach human PAI-1 mutants comprising K176A, K207A, or K263A (please refer to the entire specification particularly the abstract; “Identification of the CDE-096 Binding Site”; Figures 5 and 6; “Inhibitory Mechanism Against Protease Binding”; “Inhibitory Mechanism Against Vitronectin Binding”).
However, Li et al. do not teach a Fc fusion.
For present claims 1 and 4, Wu et al. teach the benefits of conjugating Fc to polypeptides including extended half-life (please refer to the entire specification particularly the abstract; Introduction; Table 2; Distinct PK Characteristics of Peptibodies).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. addition of Fc extends serum half-life) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. fusing Fc to polypeptides) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” (e.g. making fusion polypeptides with Fc to extend serum half-life). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Li et al. and Wu et al. for claims 1 and 4 were considered but are not persuasive for the following reasons.
Applicants contend that the examiner of record relied on references that only teach individual mutations of PAI-1 and not references that teach a combination of mutations as presently claimed. Applicants also contend that since the Fc fusion reference does not teach PAI-1, the reference would not be combined with the PAI-1 reference.
Applicants’ arguments are not convincing since the teachings of Li et al. and Wu et al. render the PAI-1 variant of the instant claims prima facie obvious. Present independent claim 1 requires one or more mutations of K176A, K207A, and/or K263A and dependent claim 4 requires at least one the mutations to be K207A. Li et al. teach PAI-1 variants of K176A, K207A, or K263A (see Figure 5F).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. addition of Fc extends serum half-life) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. fusing Fc to polypeptides) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” (e.g. making fusion polypeptides with Fc to extend serum half-life). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Claims 1 and 4 are rejected under 35 U.S.C. 103 as being unpatentable over Lawrence et al. WO 97/39028 published October 23, 1997; Wu et al., 2014, Pharmacokinetics of Peptide-Fc Fusion Proteins, Journal of Pharmaceutical Sciences, 103: 53-64; and Li et al., 2013, Mechanistic characterization and crystal structure of a small molecule inactivator bound to plasminogen activator inhibitor-1, PNAS, E4941-E4949.
For present claims 1 and 4, Lawrence et al. teach human PAI-1 mutants comprising I91L, Q123K, V343A, and/or R346V which inhibit neutrophil elastase activity and vitronectin binding (please refer to the entire specification particularly the abstract; Description; Figures; Examples; claims; pages 1, 2, 4-11, 13-15, 20, 22, 23, 24, 26, 30, 67-71, 89).
However, Lawrence et al. do not teach a Fc fusion.
For present claims 1 and 4, Wu et al. teach the benefits of conjugating Fc to polypeptides including extended half-life (please refer to the entire specification particularly the abstract; Introduction; Table 2; Distinct PK Characteristics of Peptibodies).
However, Lawrence et al. do not teach a K207A mutation.
For present claims 1 and 4, Li et al. teach human PAI-1 mutants comprising K176A, K207A, or K263A (please refer to the entire specification particularly the abstract; “Identification of the CDE-096 Binding Site”; Figures 5 and 6; “Inhibitory Mechanism Against Protease Binding”; “Inhibitory Mechanism Against Vitronectin Binding”).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. addition of Fc extends serum half-life; various mutants of PAI-1 with known functions) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. fusing Fc to polypeptides; PAI-1 mutagenesis) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” (e.g. making fusion polypeptides with Fc to extend serum half-life). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Lawrence et al.; Wu et al.; and Li et al. for claims 1 and 4 were considered but are not persuasive for the following reasons.
Applicants contend that the examiner of record relied on references that only teach individual mutations of PAI-1 and not references that teach a combination of mutations as presently claimed. Applicants also contend that since the Fc fusion reference does not teach PAI-1, the reference would not be combined with the PAI-1 reference.
Applicants’ arguments are not convincing since the teachings of Lawrence et al.; Wu et al.; and Li et al. render the PAI-1 variant of the instant claims prima facie obvious.
Present independent claim 1 requires one or more mutations of I91L, Q123K, V343A and/or R346V.
Lawrence et al. teaches single mutations of V343A or R346V and multiple mutations of V343A and/or R346V alone or in combination with I91L and/or Q123K (please refer to the entire specification particularly pages 14, 15, 20, 22, 24, 26, 30; claims).
Present independent claim 1 requires one or more mutations of K176A, K207A, and/or K263A and dependent claim 4 requires at least one the mutations to be K207A.
Li et al. teach PAI-1 variants of K176A, K207A, or K263A (see Figure 5F).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. addition of Fc extends serum half-life; various mutants of PAI-1 with known functions) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. fusing Fc to polypeptides; PAI-1 mutagenesis) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” (e.g. making fusion polypeptides with Fc to extend serum half-life). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Claims 1, 5, and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Xu et al., 2004, Conservation of Critical Functional Domains in Murine Plasminogen Activator Inhibitor-1, The Journal of Biological Chemistry, 279(17): 17914-17920 and Wu et al., 2014, Pharmacokinetics of Peptide-Fc Fusion Proteins, Journal of Pharmaceutical Sciences, 103: 53-64.
For present claims 1, 5, and 6, Xu et al. teach PAI-1 mutants comprising Q123A and/or R101A (please refer to the entire specification particularly the abstract; Figures 1-5). Please note: Xu et al. teaches murine PAI-1, however, mutation of conserved residues in different species (e.g. human) would be an obvious variation.
However, Xu et al. does not teach a Fc fusion.
For present claims 1, 5, and 6, Wu et al. teach the benefits of conjugating Fc to polypeptides including extended half-life (please refer to the entire specification particularly the abstract; Introduction; Table 2; Distinct PK Characteristics of Peptibodies).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. addition of Fc extends serum half-life) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. fusing Fc to polypeptides) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” (e.g. making fusion polypeptides with Fc to extend serum half-life). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Xu et al. and Wu et al. for claims 1, 5, and 6 were considered but are not persuasive for the following reasons.
Applicants contend that the examiner of record relied on references that only teach individual mutations of PAI-1 and not references that teach a combination of mutations as presently claimed. Applicants also contend that since the Fc fusion reference does not teach PAI-1, the reference would not be combined with the PAI-1 reference.
Applicants’ arguments are not convincing since the teachings of Xu et al. and Wu et al. render the PAI-1 variant of the instant claims prima facie obvious.
Present independent claim 1 requires one or more of R101A and/or Q123K. Present dependent claims 5 and 6 require b) R101A and Q123K.
Xu et al. teach PAI-1 with R101A and/or Q123K (see the abstract; Figures 1-5).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. addition of Fc extends serum half-life) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. fusing Fc to polypeptides) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” (e.g. making fusion polypeptides with Fc to extend serum half-life). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Claims 1, 4, 5, and 6 are rejected under 35 U.S.C. 103 as being unpatentable over Lawrence et al. WO 97/39028 published October 23, 1997; Wu et al., 2014, Pharmacokinetics of Peptide-Fc Fusion Proteins, Journal of Pharmaceutical Sciences, 103: 53-64; Li et al., 2013, Mechanistic characterization and crystal structure of a small molecule inactivator bound to plasminogen activator inhibitor-1, PNAS, E4941-E4949; and Xu et al., 2004, Conservation of Critical Functional Domains in Murine Plasminogen Activator Inhibitor-1, The Journal of Biological Chemistry, 279(17): 17914-17920.
For present claims 1, 4, 5, and 6, Lawrence et al. teach human PAI-1 mutants comprising I91L, Q123K, V343A, and/or R346V which inhibit neutrophil elastase activity and vitronectin binding (please refer to the entire specification particularly the abstract; Description; Figures; Examples; claims; pages 1, 2, 4-11, 13-15, 20, 22, 23, 24, 26, 30, 67-71, 89).
However, Lawrence et al. do not teach a Fc fusion.
For present claims 1, 4, 5, and 6, Wu et al. teach the benefits of conjugating Fc to polypeptides including extended half-life (please refer to the entire specification particularly the abstract; Introduction; Table 2; Distinct PK Characteristics of Peptibodies).
However, Lawrence et al. do not teach a K207A mutation.
For present claims 1, 4, 5, and 6, Li et al. teach human PAI-1 mutants comprising K176A, K207A, or K263A (please refer to the entire specification particularly the abstract; “Identification of the CDE-096 Binding Site”; Figures 5 and 6; “Inhibitory Mechanism Against Protease Binding”; “Inhibitory Mechanism Against Vitronectin Binding”).
However, Lawrence et al. do not teach a R101A mutation.
For present claims 1, 5, and 6, Xu et al. teach PAI-1 mutants comprising Q123A and/or R101A (please refer to the entire specification particularly the abstract; Figures 1-5). Please note: Xu et al. teaches murine PAI-1, however, mutation of conserved residues in different species (e.g. human) would be an obvious variation.
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. addition of Fc extends serum half-life; various mutants of PAI-1 with known functions) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. fusing Fc to polypeptides; PAI-1 mutagenesis) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” (e.g. making fusion polypeptides with Fc to extend serum half-life). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection under 35 USC 103 as being unpatentable over Lawrence et al.; Wu et al.; Li et al.; and Xu et al. for claims 1 and 4-6 were considered but are not persuasive for the following reasons.
Applicants contend that contend that the examiner of record relied on references that only teach individual mutations of PAI-1 and not references that teach a combination of mutations as presently claimed. Applicants also contend that since the Fc fusion reference does not teach PAI-1, the reference would not be combined with the PAI-1 reference.
Applicants’ arguments are not convincing since the teachings of Lawrence et al.; Wu et al.; Li et al.; and Xu et al. render the PAI-1 variant of the instant claims prima facie obvious.
Present independent claim 1 requires one or more mutations of I91L, Q123K, V343A and/or R346V.
Lawrence et al. teaches single mutations of V343A or R346V and multiple mutations of V343A and/or R346V alone or in combination with I91L and/or Q123K (please refer to the entire specification particularly pages 14, 15, 20, 22, 24, 26, 30; claims).
Present independent claim 1 requires one or more mutations of K176A, K207A, and/or K263A and dependent claim 4 requires at least one the mutations to be K207A.
Li et al. teach PAI-1 variants of K176A, K207A, or K263A (see Figure 5F).
Present independent claim 1 requires one or more of R101A and/or Q123K. Present dependent claims 5 and 6 require b) R101A and Q123K.
Xu et al. teach PAI-1 with R101A and/or Q123K (see the abstract; Figures 1-5).
Present dependent claims 5 and 6 require a combination of I91L, R101A, Q123K, K207A, V343A, and R346V which the combination of Lawrence et al., Li et al. and Xu et al. teach.
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. addition of Fc extends serum half-life; various mutants of PAI-1 with known functions) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. fusing Fc to polypeptides; PAI-1 mutagenesis) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” (e.g. making fusion polypeptides with Fc to extend serum half-life). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
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.
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 7,388,074 in view of Wu et al., 2014, Pharmacokinetics of Peptide-Fc Fusion Proteins, Journal of Pharmaceutical Sciences, 103: 53-64.
U.S. Patent No. 7,388,074 claims PAI-1 with I91L, V343A, and/or R346V mutations.
Wu et al. teach the benefits of conjugating Fc to polypeptides including extended half-life (please refer to the entire specification particularly the abstract; Introduction; Table 2; Distinct PK Characteristics of Peptibodies).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. addition of Fc extends serum half-life) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. fusing Fc to polypeptides) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” (e.g. making fusion polypeptides with Fc to extend serum half-life). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 7,388,074 in view of Wu et al. for claim 1 were considered but are not persuasive for the following reasons.
Applicant requests that the rejection be held in abeyance.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 7,388,074 in view of Wu et al. renders obvious the PAI-1 variant of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
Claims 1, 4, 5, and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13 of U.S. Patent No. 7,388,074 in view of Wu et al., 2014, Pharmacokinetics of Peptide-Fc Fusion Proteins, Journal of Pharmaceutical Sciences, 103: 53-64; Li et al., 2013, Mechanistic characterization and crystal structure of a small molecule inactivator bound to plasminogen activator inhibitor-1, PNAS, E4941-E4949; and Xu et al., 2004, Conservation of Critical Functional Domains in Murine Plasminogen Activator Inhibitor-1, The Journal of Biological Chemistry, 279(17): 17914-17920.
U.S. Patent No. 7,388,074 claims PAI-1 with I91L, V343A, and/or R346V mutations.
Wu et al. teach the benefits of conjugating Fc to polypeptides including extended half-life (please refer to the entire specification particularly the abstract; Introduction; Table 2; Distinct PK Characteristics of Peptibodies).
Li et al. teach human PAI-1 mutants comprising K176A, K207A, or K263A (please refer to the entire specification particularly the abstract; “Identification of the CDE-096 Binding Site”; Figures 5 and 6; “Inhibitory Mechanism Against Protease Binding”; “Inhibitory Mechanism Against Vitronectin Binding”).
Xu et al. teach PAI-1 mutants comprising Q123A and/or R101A (please refer to the entire specification particularly the abstract; Figures 1-5).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. addition of Fc extends serum half-life; various mutants of PAI-1 with known functions) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. fusing Fc to polypeptides; PAI-1 mutagenesis) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” (e.g. making fusion polypeptides with Fc to extend serum half-life). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 7,388,074 in view of Wu et al.; Li et al.; and Xu et al. for claims 1 and 4-6 were considered but are not persuasive for the following reasons.
Applicant requests that the rejection be held in abeyance.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 7,388,074 in view of Wu et al.; Li et al.; and Xu et al. renders obvious the PAI-1 variant of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 6,489,143 in view of Wu et al., 2014, Pharmacokinetics of Peptide-Fc Fusion Proteins, Journal of Pharmaceutical Sciences, 103: 53-64.
U.S. Patent No. 6,489,143 claims PAI-1 with I91L, V343A, and/or R346V mutations (please note the method claims to produce the protein from the claimed nucleic acids).
Wu et al. teach the benefits of conjugating Fc to polypeptides including extended half-life (please refer to the entire specification particularly the abstract; Introduction; Table 2; Distinct PK Characteristics of Peptibodies).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. addition of Fc extends serum half-life) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. fusing Fc to polypeptides) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” (e.g. making fusion polypeptides with Fc to extend serum half-life). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 6,489,143 in view of Wu et al. for claim 1 were considered but are not persuasive for the following reasons.
Applicant requests that the rejection be held in abeyance.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 6,489,143 in view of Wu et al. renders obvious the PAI-1 variant of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
Claims 1, 4, 5, and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 6,489,143 in view of Wu et al., 2014, Pharmacokinetics of Peptide-Fc Fusion Proteins, Journal of Pharmaceutical Sciences, 103: 53-64; Li et al., 2013, Mechanistic characterization and crystal structure of a small molecule inactivator bound to plasminogen activator inhibitor-1, PNAS, E4941-E4949; and Xu et al., 2004, Conservation of Critical Functional Domains in Murine Plasminogen Activator Inhibitor-1, The Journal of Biological Chemistry, 279(17): 17914-17920.
U.S. Patent No. 6,489,143 claims PAI-1 with I91L, V343A, and/or R346V mutations (please note the method claims to produce the protein from the claimed nucleic acids).
Wu et al. teach the benefits of conjugating Fc to polypeptides including extended half-life (please refer to the entire specification particularly the abstract; Introduction; Table 2; Distinct PK Characteristics of Peptibodies).
Li et al. teach human PAI-1 mutants comprising K176A, K207A, or K263A (please refer to the entire specification particularly the abstract; “Identification of the CDE-096 Binding Site”; Figures 5 and 6; “Inhibitory Mechanism Against Protease Binding”; “Inhibitory Mechanism Against Vitronectin Binding”).
Xu et al. teach PAI-1 mutants comprising Q123A and/or R101A (please refer to the entire specification particularly the abstract; Figures 1-5).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. addition of Fc extends serum half-life; various mutants of PAI-1 with known functions) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. fusing Fc to polypeptides; PAI-1 mutagenesis) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” (e.g. making fusion polypeptides with Fc to extend serum half-life). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over 1-15 of U.S. Patent No. 6,489,143 in view of Wu et al.; Li et al.; and Xu et al. for claims 1 and 4-6 were considered but are not persuasive for the following reasons.
Applicant requests that the rejection be held in abeyance.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 6,489,143 in view of Wu et al.; Li et al.; and Xu et al. renders obvious the PAI-1 variant of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
Claim 1 is rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 6,103,498 in view of Wu et al., 2014, Pharmacokinetics of Peptide-Fc Fusion Proteins, Journal of Pharmaceutical Sciences, 103: 53-64.
U.S. Patent No. 6,103,498 claims PAI-1 with I91L, V343A, and/or R346V mutations.
Wu et al. teach the benefits of conjugating Fc to polypeptides including extended half-life (please refer to the entire specification particularly the abstract; Introduction; Table 2; Distinct PK Characteristics of Peptibodies).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. addition of Fc extends serum half-life) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. fusing Fc to polypeptides) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” (e.g. making fusion polypeptides with Fc to extend serum half-life). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 6,103,498 in view of Wu et al. for claim 1 were considered but are not persuasive for the following reasons.
Applicant requests that the rejection be held in abeyance.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 6,103,498 in view of Wu et al. renders obvious the PAI-1 variant of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
Claims 1, 4, 5, and 6 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-14 of U.S. Patent No. 6,103,498 in view of Wu et al., 2014, Pharmacokinetics of Peptide-Fc Fusion Proteins, Journal of Pharmaceutical Sciences, 103: 53-64; Li et al., 2013, Mechanistic characterization and crystal structure of a small molecule inactivator bound to plasminogen activator inhibitor-1, PNAS, E4941-E4949; and Xu et al., 2004, Conservation of Critical Functional Domains in Murine Plasminogen Activator Inhibitor-1, The Journal of Biological Chemistry, 279(17): 17914-17920.
U.S. Patent No. 6,103,498 claims PAI-1 with I91L, V343A, and/or R346V mutations.
Wu et al. teach the benefits of conjugating Fc to polypeptides including extended half-life (please refer to the entire specification particularly the abstract; Introduction; Table 2; Distinct PK Characteristics of Peptibodies).
Li et al. teach human PAI-1 mutants comprising K176A, K207A, or K263A (please refer to the entire specification particularly the abstract; “Identification of the CDE-096 Binding Site”; Figures 5 and 6; “Inhibitory Mechanism Against Protease Binding”; “Inhibitory Mechanism Against Vitronectin Binding”).
Xu et al. teach PAI-1 mutants comprising Q123A and/or R101A (please refer to the entire specification particularly the abstract; Figures 1-5).
All the claimed elements were known in the prior art and one skilled in the art could have combined the elements as claimed by known methods with no change in the respective functions and the combination would have yielded predictable results (i.e. addition of Fc extends serum half-life; various mutants of PAI-1 with known functions) to one of ordinary skill in the art at the time of the invention. The claims would have been obvious because a particular known technique (i.e. fusing Fc to polypeptides; PAI-1 mutagenesis) was recognized as part of the ordinary capabilities of one skilled in the art. The claims would have been obvious because “a person of ordinary skill has good reason to pursue the known options within his or her technical grasp. If this leads to the anticipated success, it is likely the product not of innovation but of ordinary skill and common sense.” (e.g. making fusion polypeptides with Fc to extend serum half-life). See KSR International Co. v. Teleflex Inc., 82 USPQ2d 1385 (U.S. 2007).
Arguments and Response
Applicants’ arguments directed to the rejection on the ground of nonstatutory obviousness-type double patenting as being unpatentable over U.S. Patent No. 6,103,498 in view of Wu et al.; Li et al.; and Xu et al. for claims 1 and 4-6 were considered but are not persuasive for the following reasons.
Applicant requests that the rejection be held in abeyance.
Applicants’ arguments are not convincing since the claimed invention of U.S. Patent No. 6,103,498 in view of Wu et al.; Li et al.; and Xu et al. renders obvious the PAI-1 variant of the instant claims. In addition, while a request may be made that objections or requirements as to form not necessary to further consideration of the claims be held in abeyance until allowable subject matter is indicated, the present is a rejection and will not be held in abeyance (see MPEP § 714.02).
Conclusion
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
Jafari et al., 2017, Fc-fusion Proteins in Therapy: An Updated View, Current Medicinal Chemistry, 24: 1228-1237.
U.S. Patent Application Publications 2010/0137194 (see paragraph 555) and 2010/0286053 (see paragraph 79) both teach PAI-1 mutants comprising R101A and Q123K.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
Future Communications
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/AMBER D STEELE/Primary Examiner, Art Unit 1658