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 .
Election/Restrictions and Claim Status
Applicants’ amendments and arguments filed 5/11/26 are acknowledged. Any objection or rejection from the 2/11/26 office action that is not addressed below is withdrawn based on the amendments.
Previously Group 1 and the species of SEQ ID NO:8, mannitol, glycylglycine and polysorbate-80 were elected.
Claim 58 remains withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim. Applicant timely traversed the restriction (election) requirement in the reply filed on 12/9/25.
Newly added claim 65 requires a substitution that is not present in the elected species of SEQ ID NO:8.
Claim 65 is withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on 12/9/25.
Newly submitted claims 66 and 68 are directed to an invention that lacks unity with the invention originally claimed for the same reasons as set forth in the 9/11/25 restriction requirement (and further based on the 102/103 rejections set forth below).
Since applicant has received an action on the merits for the originally presented invention, this invention has been constructively elected by original presentation for prosecution on the merits. Accordingly, claims 66 and 68 are withdrawn from consideration as being directed to a nonelected invention. See 37 CFR 1.142(b) and MPEP § 821.03.
To preserve a right to petition, the reply to this action must distinctly and specifically point out supposed errors in the restriction requirement. Otherwise, the election shall be treated as a final election without traverse. Traversal must be timely. Failure to timely traverse the requirement will result in the loss of right to petition under 37 CFR 1.144. If claims are subsequently added, applicant must indicate which of the subsequently added claims are readable upon the elected invention.
Should applicant traverse on the ground that the inventions are not patentably distinct, applicant should submit evidence or identify such evidence now of record showing the inventions to be obvious variants or clearly admit on the record that this is the case. In either instance, if the examiner finds one of the inventions unpatentable over the prior art, the evidence or admission may be used in a rejection under 35 U.S.C. 103 or pre-AIA 35 U.S.C. 103(a) of the other invention.
Claims to the elected species are rejected as set forth below. Although certain claims (see claim 57) require sucrose which was not elected as a species, such claims are included in the instant examination in order to advance prosecution. Any relevant art that was uncovered during the search for the elected species is cited herein in order to advance prosecution.
Newly added claim 67 is included in the instant examination.
Claims 3-4, 6-8, 10, 12-23, 26-27, 29-35, 37-38, 40-47 and 49-55 have been canceled.
Claims 1-2, 5, 9, 11, 24-25, 28, 36, 39, 48, 56-57, 59-64 and 67 are being examined.
Priority
The priority information is found in the filing receipt dated 10/12/23.
Claim Rejections - 35 USC § 112
The rejection set forth below is maintained from the previous office action.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claim 36 is rejected 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.
Claim 36 recites ‘buffers selected from’ and then recites ‘histidine and glycyl-glycine, non-phosphate buffers…’. The use of the word ‘and’ within a group (specifically where it is not separating the last 2 options) makes it unclear if specific combinations of buffers are intended or if the word ‘and’ is merely extraneous.
Although unclear, the claims have been given the broadest reasonable interpretation consistent with the specification.
Response to Arguments - 112
Applicant's arguments filed 5/11/26 have been fully considered but they are not persuasive with respect to the rejection set forth above.
Although applicants argue that the claims have been amended, none of the amendments address the rejection set forth above.
Claim Rejections - 35 USC § 102
Claims were previously rejected based on the reference cited below. Since the claims have been amended (including the addition of a new claim), the rejection is updated to correspond to the instant claims.
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claim(s) 1-2, 5, 9, 11, 36, 48, 56, 59-60, 62-63 and 67 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Consalvo et al. (WO 2012/174397; as cited with IDS 5/12/23; ‘Consalvo’).
Consalvo teach SEQ ID NO:7 (also known as UGP025) corresponds to amino acids 2-48 of human Annexin 1 where residue 24 is Leu and the polypeptide is amidated at its C-terminus (page 8 3rd complete paragraph) and that the peptide was tested in assays (figure 8 for example). Consalvo teach that the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate (pages 19-20 connecting paragraph). Consalvo teach that the HPLC was used for peptide purification and that separation was achieved using a linear gradient from 0% A (10 mM Tris, pH 8) to 20% B (10 mM Tris, 0.5 NaCl pH 8) (page 20 lines 13-20). Consalvo also teach peptide elution at pH 8.5 (page 19 last complete paragraph). Consalvo teach that the peptides were lyophilized (page 20 lines 10-12).
In relation to the peptide as recited in claims 1, 48, 56, 59 and 62-63, Consalvo teach SEQ ID NO:7 (also known as UGP025) corresponds to amino acids 2-48 of human Annexin 1 where residue 24 is Leu and the polypeptide is amidated at its C-terminus (page 8 3rd complete paragraph) which corresponds to instant SEQ ID NO:8. Since SEQ ID NO:7 of Consalvo corresponds to the elected species it is interpreted as meeting the limitation of claims 9 and 60.
In relation to the solvent as recited in claim 1bi, Consalvo teach that the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate (pages 19-20 connecting paragraph). Since Tris was used, water would have been present. It is noted that Consalvo teach that the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate (pages 19-20 connecting paragraph) where ascorbate is a carbohydrate.
In relation to the pH of claims 1-2, 5 and 59, Consalvo teach examples with a pH of 7 (the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate pages 19-20 connecting paragraph) and a pH of 8 (the HPLC was used for peptide purification and that separation was achieved using a linear gradient from 0% A (10 mM Tris, pH 8) to 20% B (10 mM Tris, 0.5 NaCl pH 8) page 20 lines 13-20) as well as a pH of 8.5 (page 19 last complete paragraph).
In relation to the ionic strength of claim 59b, Consalvo teach that the HPLC was used for peptide purification and that separation was achieved using a linear gradient from 0% A (10 mM Tris, pH 8) to 20% B (10 mM Tris, 0.5 NaCl pH 8) (page 20 lines 13-20). Since a linear gradient was used, intermediate concentrations of NaCl would necessarily have been present.
In relation to claims 11 and 61, Consalvo teach that the amidation was carried out at 0.5 mg/ml of the peptide (pages 19-20 connecting paragraph).
In relation to claim 36, Consalvo teach examples with Tris buffer ( the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate pages 19-20 connecting paragraph; the HPLC was used for peptide purification and that separation was achieved using a linear gradient from 0% A (10 mM Tris, pH 8) to 20% B (10 mM Tris, 0.5 NaCl pH 8) page 20 lines 13-20).
In relation to claim 67, Consalvo teach that the peptides were lyophilized (page 20 lines 10-12).
Response to Arguments - 102
Applicant's arguments filed 5/11/26 have been fully considered but they are not persuasive with respect to the rejection set forth above.
Although applicants argue that the claims have been amended, the amended claims are addressed above.
Although applicants argue that ascorbate is only taught in the context of certain peptides, Consalvo expressly teach SEQ ID NO:7 (also known as UGP025) corresponds to amino acids 2-48 of human Annexin 1 where residue 24 is Leu and the polypeptide is amidated at its C-terminus (page 8 3rd complete paragraph). Consalvo teach that ‘C-terminal alpha-amidation (if required) was carried out’ using rPAM and then Consalvo recites what was used in conjunction with rPAM (pages 19-20 connecting paragraph). Since SEQ ID NO:7 is amidated at its C-terminus then amidation of the C-terminus is required and would have been done via the method taught by Consalvo (pages 19-20 connecting paragraph) which contains ascorbate.
Although applicants argue about glycine-extended peptides, Consalvo teach that ‘C-terminal alpha-amidation (if required) was carried out’ using rPAM and then Consalvo recites what was used in conjunction with rPAM (pages 19-20 connecting paragraph). Thus, the method is not limited only to particular peptides but is for those in which C-terminal alpha-amidation is required. Consalvo expressly teach SEQ ID NO:7 (also known as UGP025) corresponds to amino acids 2-48 of human Annexin 1 where residue 24 is Leu and the polypeptide is amidated at its C-terminus (page 8 3rd complete paragraph).
Although applicants argue that a liquid pharmaceutical is not taught, Consalvo teach that peptides were lyophilized but the prior step (or steps) require a peptide in a liquid composition (see pages 19-20). Further, Consalvo expressly teach liquid solutions (page 23 lines 6-14).
Although applicants argue about a certain ionic strength or the presence of a carbohydrate or sugar alcohol, claim 59 does not require a carbohydrate or sugar alcohol. Claim 1b recites either option i or ii and option i does not require a specific ionic strength. The specific claim limitations are addressed in the rejection set forth above.
Claim Rejections - 35 USC § 103
Claims were previously rejected based on the references cited below. Since the claims have been amended (including the addition of a new claim), the rejections are updated to correspond to the instant claims.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claim(s) 1-2, 5, 9, 11, 24-25, 28, 36, 48, 56, 59-64 and 67 is/are rejected under 35 U.S.C. 103 as being unpatentable over Consalvo et al. (WO 2012/174397; as cited with IDS 5/12/23; ‘Consalvo’) in view of Callahan et al. (US 2009/0258017; ‘Callahan’).
Consalvo teach peptides for medical use as anti-inflammatory agents (abstract). Consalvo teach SEQ ID NO:7 (also known as UGP025) corresponds to amino acids 2-48 of human Annexin 1 where residue 24 is Leu and the polypeptide is amidated at its C-terminus (page 8 3rd complete paragraph) and that the peptide was tested in assays (figure 8 for example). Consalvo teach that the peptide can be delivered by injection at various concentrations (page 22 line 27-page 23 line 5). Consalvo specifically teach i.v. administration of UGP025 (page 16 lines 22-29). Consalvo teach that the compositions may include typical pharmaceutical excipients, diluents or carriers such as water, saline and glycerol (page 23 lines 6-14). Consalvo teach solid forms that are suitable for solution prior to injection (page 23 lines 11-14). Consalvo teach that the peptides were lyophilized (page 20 lines 10-12). Consalvo teach peptide solutions at various pH values including using a Tris buffer at a pH of 7 (the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate pages 19-20 connecting paragraph) and a pH of 8 (the HPLC was used for peptide purification and that separation was achieved using a linear gradient from 0% A (10 mM Tris, pH 8) to 20% B (10 mM Tris, 0.5 NaCl pH 8) page 20 lines 13-20) as well as a pH of 8.5 (page 19 last complete paragraph). Consalvo teach that the peptides were lyophilized (page 20 lines 10-12).
Consalvo does not teach a specific example with a combination of mannitol and sucrose for example.
Callahan teach that purified peptides are only marginally stable in an aqueous state and undergo chemical and physical degradation during processing and storage (section 0016). Callahan teach that a lyophilized formulation usually comprises a buffer, a bulking agent and a stabilizer and the various components have particular functions (section 0117 and Table A). Callahan teach that the role of formulation excipients is to provide stabilization against stresses (section 0118). Callahan teach that those skilled in the art will know what amount or range of excipient can be included in any particular formulation to achieve one that promotes retention of stability and that the amount and type of salt can be selected as well as the type of sugar (section 0119). Callahan teach that the excipients share an interdependency (section 0122). Callahan teach the known effects of salts (sections 0147-0148) and teach that salt concentrations are used to adjust the ionic strength and are generally limited to less than 150 mM (section 0149) and recognize Na+ and Cl- as a cation and anion for salts (Table C page 17). Callahan teach that mannitol is a commonly used bulking agent (section 0133) and that polyols include mannitol, sucrose and glycerol (section 0135). Callahan recognizes a combination of stabilizers to reduce aggregation and degradation (section 0138). Callahan teach a range of amounts of the stabilizer and bulking agents (sections 0138-0139). Callahan teach optimizing stability by focusing on the effect of sucrose, mannitol and tween (section 0360). Callahan teach a pH buffering agent in a range of about 5 mM to about 20 mM with a pH range of about 3 to about 8 (section 0019). Callahan teach a buffer system and recognizes a pH range that includes 7.0, 8.0 and 8.3 (section 0128). Callahan teach buffering agents based on glycine (section 0131). Callahan teach a known non-ionic surfactant is Tween-80 (section 0145) and teach an example where Tween was used to inhibit aggregation (sections 0358 and 0366). Callahan teach a range of amounts of Tween (section 0145). Callahan recognizes a wide range of pharmacologically active peptides (section 0014 and Table 2). Callahan teach that any number of peptides may be used with the present invention (sections 0208-0247).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Consalvo based on the specific teachings and suggestions of Consalvo. Consalvo teach SEQ ID NO:7 (also known as UGP025) corresponds to amino acids 2-48 of human Annexin 1 where residue 24 is Leu and the polypeptide is amidated at its C-terminus (page 8 3rd complete paragraph) and that the peptide was tested in assays (figure 8 for example). Consalvo teach that the peptide can be delivered by injection at various concentrations (page 22 line 27-page 23 line 5). Consalvo specifically teach i.v. administration of UGP025 (page 16 lines 22-29). Consalvo teach solid forms that are suitable for solution prior to injection (page 23 lines 11-14). Thus one would have been motivated to prepare formulations of SEQ ID NO:7. Since Consalvo teach that the compositions may include typical pharmaceutical excipients, diluents or carriers such as water, saline and glycerol (page 23 lines 6-14) one would have been motivated to prepare compositions. Callahan provides more details about the components of the compositions. Callahan teach that purified peptides are only marginally stable in an aqueous state and undergo chemical and physical degradation during processing and storage (section 0016). Callahan teach that a lyophilized formulation usually comprises a buffer, a bulking agent and a stabilizer and the various components have particular functions (section 0117 and Table A).
Consalvo teach that the compositions may include typical pharmaceutical excipients, diluents or carriers such as saline (page 23 lines 6-14). Since Callahan teach the known effects of salts (sections 0147-0148) and teach that salt concentrations are used to adjust the ionic strength and are generally limited to less than 150 mM (section 0149) and recognize Na+ and Cl- as a cation and anion for salts (Table C page 17) one would have been motivated to include NaCl within such range. Further, Callahan teach that those skilled in the art will know what amount or range of components including salt can be included (section 0119).
Consalvo teach that the compositions may include typical pharmaceutical excipients, diluents or carriers such as glycerol (page 23 lines 6-14). Callahan teach that polyols include mannitol, sucrose and glycerol (section 0135) and that mannitol is a commonly used bulking agent (section 0133). Callahan recognizes a combination of stabilizers to reduce aggregation and degradation (section 0138). Callahan teach optimizing stability by focusing on the effect of sucrose, mannitol and tween (section 0360). Callahan teach a known non-ionic surfactant is Tween-80 (section 0145) and teach an example where Tween was used to inhibit aggregation (sections 0358 and 0366). Thus, one would have been motivated to include sucrose, mannitol and Tween-80 in the compositions based on their known effects. Callahan teach that those skilled in the art will know what amount or range of excipient can be included in any particular formulation (section 0119). Callahan teach a range of amounts of the stabilizer and bulking agents (sections 0138-0139).
Consalvo teach peptide solutions at various pH values including using a Tris buffer at a pH of 7 (the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate pages 19-20 connecting paragraph) and a pH of 8 (the HPLC was used for peptide purification and that separation was achieved using a linear gradient from 0% A (10 mM Tris, pH 8) to 20% B (10 mM Tris, 0.5 NaCl pH 8) page 20 lines 13-20) as well as a pH of 8.5 (page 19 last complete paragraph). Callahan teach a pH buffering agent in a range of amount 5 mM to about 20 mM with a pH range of about 3 to about 8 (section 0019). Callahan teach a buffer system and recognizes a pH range that includes 7.0, 8.0 and 8.3 (section 0128). Consalvo teach that the compositions may include typical pharmaceutical excipients, diluents or carriers such as water (page 23 lines 6-14) and water is known to be a component of buffers. Thus, one would have been motivated to make buffered solutions with those amounts.
One would have had a reasonable expectation of success because Consalvo teach a specific peptide (SEQ ID NO:7 (also known as UGP025) corresponds to amino acids 2-48 of human Annexin 1 where residue 24 is Leu and the polypeptide is amidated at its C-terminus (page 8 3rd complete paragraph)) and that the peptide was tested in assays (figure 8 for example). Further, Callahan recognizes a wide range of pharmacologically active peptides (section 0014 and Table 2). Callahan teach that any number of peptides may be used with the present invention (sections 0208-0247). In the instant case, 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.
In relation to the peptide as recited in claims 1, 48, 56, 59 and 62-63, Consalvo teach SEQ ID NO:7 (also known as UGP025) corresponds to amino acids 2-48 of human Annexin 1 where residue 24 is Leu and the polypeptide is amidated at its C-terminus (page 8 3rd complete paragraph) which corresponds to instant SEQ ID NO:8. Since SEQ ID NO:7 of Consalvo corresponds to the elected species it is interpreted as meeting the limitation of claims 9 and 60.
In relation to the solvent as recited in claim 1bi, Consalvo teach that the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate (pages 19-20 connecting paragraph). Since Tris was used, water would have been present. It is noted that Consalvo teach that the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate (pages 19-20 connecting paragraph) where ascorbate is a carbohydrate.
In relation to the ionic strength of claims 1bii and 59b, Callahan teach the known effects of salts (sections 0147-0148) and teach that salt concentrations are used to adjust the ionic strength and are generally limited to less than 150 mM (section 0149) and recognize Na+ and Cl- as a cation and anion for salts (Table C page 17) so one would have been motivated to include NaCl within such range. Further, Callahan teach that those skilled in the art will know what amount or range of components including salt can be included (section 0119). MPEP 2144.05 I recognizes that where the claimed range overlaps or lies inside ranges of the prior art a prima facie case of obviousness exists (1 micromolar to 50 mM lies inside less than 150 mM).
In relation to any carbohydrate or sugar alcohol of claims 1bi, 1bii, 24, 25, 28 and 64, Consalvo teach that the compositions may include typical pharmaceutical excipients, diluents or carriers such as glycerol (page 23 lines 6-14). Callahan teach that polyols include mannitol, sucrose and glycerol (section 0135) and that mannitol is a commonly used bulking agent (section 0133). Callahan recognizes a combination of stabilizers to reduce aggregation and degradation (section 0138). Callahan teach optimizing stability by focusing on the effect of sucrose and mannitol (section 0360). Thus, one would have been motivated to include sucrose and mannitol in the compositions based on their known effects. Callahan teach that those skilled in the art will know what amount or range of excipient can be included in any particular formulation (section 0119). MPEP 2144.05 I recognizes that where the claimed range overlaps or lies inside ranges of the prior art a prima facie case of obviousness exists. Callahan teach a range of amounts of the stabilizer and bulking agents (sections 0138-0139).
In relation to the pH of claims 1-2, 5 and 59, Consalvo teach examples with a pH of 7 ( the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate pages 19-20 connecting paragraph) and a pH of 8 (the HPLC was used for peptide purification and that separation was achieved using a linear gradient from 0% A (10 mM Tris, pH 8) to 20% B (10 mM Tris, 0.5 NaCl pH 8) page 20 lines 13-20) as well as a pH of 8.5 (page 19 last paragraph). Further, Callahan teach a pH buffering agent in a range of about 5 mM to about 20 mM with a pH range of about 3 to about 8 (section 0019). Callahan teach a buffer system and recognizes a pH range that includes 7.0, 8.0 and 8.3 (section 0128).
In relation to claims 11 and 61, Consalvo teach that the amidation was carried out at 0.5 mg/ml of the peptide (pages 19-20 connecting paragraph). Further, Consalvo teach that the effective amount will vary and includes between 10 micrograms/ml and 1000 micrograms/ml (page 23 lines 3-5 and 15-21).
In relation to claim 36, Consalvo teach examples with Tris buffer ( the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate pages 19-20 connecting paragraph; the HPLC was used for peptide purification and that separation was achieved using a linear gradient from 0% A (10 mM Tris, pH 8) to 20% B (10 mM Tris, 0.5 NaCl pH 8) page 20 lines 13-20).
In relation to claim 67, Consalvo teach that the peptides were lyophilized (page 20 lines 10-12).
Claim(s) 1-2, 5, 9, 11, 24-25, 28, 36, 39, 48, 56-57, 59-64 and 67 is/are rejected under 35 U.S.C. 103 as being unpatentable over Consalvo et al. (WO 2012/174397; as cited with IDS 5/12/23; ‘Consalvo’) in view of Callahan et al. (US 2009/0258017; ‘Callahan’) in view of Mitterer et al. (US 2014/0302592; ‘Mitterer’).
Consalvo teach peptides for medical use as anti-inflammatory agents (abstract). Consalvo teach SEQ ID NO:7 (also known as UGP025) corresponds to amino acids 2-48 of human Annexin 1 where residue 24 is Leu and the polypeptide is amidated at its C-terminus (page 8 3rd complete paragraph) and that the peptide was tested in assays (figure 8 for example). Consalvo teach that the peptide can be delivered by injection at various concentrations (page 22 line 27-page 23 line 5). Consalvo specifically teach i.v. administration of UGP025 (page 16 lines 22-29). Consalvo teach that the compositions may include typical pharmaceutical excipients, diluents or carriers such as water, saline and glycerol (page 23 lines 6-14). Consalvo teach solid forms that are suitable for solution prior to injection (page 23 lines 11-14). Consalvo teach that the peptides were lyophilized (page 20 lines 10-12). Consalvo teach peptide solutions at various pH values including using a Tris buffer at a pH of 7 (the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate pages 19-20 connecting paragraph) and a pH of 8 (the HPLC was used for peptide purification and that separation was achieved using a linear gradient from 0% A (10 mM Tris, pH 8) to 20% B (10 mM Tris, 0.5 NaCl pH 8) page 20 lines 13-20) as well as a pH of 8.5 (page 19 last complete paragraph). Consalvo teach that the peptides were lyophilized (page 20 lines 10-12).
Consalvo does not teach a specific example with glycyl-glycine and combination of mannitol and sucrose for example.
Callahan teach that purified peptides are only marginally stable in an aqueous state and undergo chemical and physical degradation during processing and storage (section 0016). Callahan teach that a lyophilized formulation usually comprises a buffer, a bulking agent and a stabilizer and the various components have particular functions (section 0117 and Table A). Callahan teach that the role of formulation excipients is to provide stabilization against stresses (section 0118). Callahan teach that those skilled in the art will know what amount or range of excipient can be included in any particular formulation to achieve one that promotes retention of stability and that the amount and type of salt can be selected as well as the type of sugar (section 0119). Callahan teach that the excipients share an interdependency (section 0122). Callahan teach the known effects of salts (sections 0147-0148) and teach that salt concentrations are used to adjust the ionic strength and are generally limited to less than 150 mM (section 0149) and recognize Na+ and Cl- as a cation and anion for salts (Table C page 17). Callahan teach that mannitol is a commonly used bulking agent (section 0133) and that polyols include mannitol, sucrose and glycerol (section 0135). Callahan recognizes a combination of stabilizers to reduce aggregation and degradation (section 0138). Callahan teach a range of amounts of the stabilizer and bulking agents (sections 0138-0139). Callahan teach optimizing stability by focusing on the effect of sucrose, mannitol and tween (section 0360). Callahan teach a pH buffering agent in a range of about 5 mM to about 20 mM with a pH range of about 3 to about 8 (section 0019). Callahan teach a buffer system and recognizes a pH range that includes 7.0, 8.0 and 8.3 (section 0128). Callahan teach buffering agents based on glycine (section 0131). Callahan teach a known non-ionic surfactant is Tween-80 (section 0145) and teach an example where Tween was used to inhibit aggregation (sections 0358 and 0366). Callahan teach a range of amounts of Tween (section 0145). Callahan recognizes a wide range of pharmacologically active peptides (section 0014 and Table 2). Callahan teach that any number of peptides may be used with the present invention (sections 0208-0247).
Mitterer teach methods of purifying applicable to annexin (claim 9). Mitterer teach that a particularly preferred buffer is Gly-Gly (buffers at pH = 7.4+-1.0) (section 0047).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of Consalvo based on the specific teachings and suggestions of Consalvo. Consalvo teach SEQ ID NO:7 (also known as UGP025) corresponds to amino acids 2-48 of human Annexin 1 where residue 24 is Leu and the polypeptide is amidated at its C-terminus (page 8 3rd complete paragraph) and that the peptide was tested in assays (figure 8 for example). Consalvo teach that the peptide can be delivered by injection at various concentrations (page 22 line 27-page 23 line 5). Consalvo specifically teach i.v. administration of UGP025 (page 16 lines 22-29). Consalvo teach solid forms that are suitable for solution prior to injection (page 23 lines 11-14). Thus one would have been motivated to prepare formulations of SEQ ID NO:7. Since Consalvo teach that the compositions may include typical pharmaceutical excipients, diluents or carriers such as water, saline and glycerol (page 23 lines 6-14) one would have been motivated to prepare compositions. Callahan provides more details about the components of the compositions. Callahan teach that purified peptides are only marginally stable in an aqueous state and undergo chemical and physical degradation during processing and storage (section 0016). Callahan teach that a lyophilized formulation usually comprises a buffer, a bulking agent and a stabilizer and the various components have particular functions (section 0117 and Table A).
Consalvo teach that the compositions may include typical pharmaceutical excipients, diluents or carriers such as saline (page 23 lines 6-14). Since Callahan teach the known effects of salts (sections 0147-0148) and teach that salt concentrations are used to adjust the ionic strength and are generally limited to less than 150 mM (section 0149) and recognize Na+ and Cl- as a cation and anion for salts (Table C page 17) one would have been motivated to include NaCl within such range. Further, Callahan teach that those skilled in the art will know what amount or range of components including salt can be included (section 0119).
Consalvo teach that the compositions may include typical pharmaceutical excipients, diluents or carriers such as glycerol (page 23 lines 6-14). Callahan teach that polyols include mannitol, sucrose and glycerol (section 0135) and that mannitol is a commonly used bulking agent (section 0133). Callahan recognizes a combination of stabilizers to reduce aggregation and degradation (section 0138). Callahan teach optimizing stability by focusing on the effect of sucrose, mannitol and tween (section 0360). Callahan teach a known non-ionic surfactant is Tween-80 (section 0145) and teach an example where Tween was used to inhibit aggregation (sections 0358 and 0366). Thus, one would have been motivated to include sucrose, mannitol and Tween-80 in the compositions based on their known effects. Callahan teach that those skilled in the art will know what amount or range of excipient can be included in any particular formulation (section 0119). Callahan teach a range of amounts of the stabilizer and bulking agents (sections 0138-0139). Callahan teach a range of amounts of Tween (section 0145).
Consalvo teach peptide solutions at various pH values including using a Tris buffer at a pH of 7 (the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate pages 19-20 connecting paragraph) and a pH of 8 (the HPLC was used for peptide purification and that separation was achieved using a linear gradient from 0% A (10 mM Tris, pH 8) to 20% B (10 mM Tris, 0.5 NaCl pH 8) page 20 lines 13-20) as well as a pH of 8.5 (page 19 last complete paragraph). Callahan teach a pH buffering agent in a range of amount 5 mM to about 20 mM with a pH range of about 3 to about 8 (section 0019). Callahan teach a buffer system and recognizes a pH range that includes 7.0, 8.0 and 8.3 (section 0128). Consalvo teach that the compositions may include typical pharmaceutical excipients, diluents or carriers such as water (page 23 lines 6-14) and water is known to be a component of buffers. Thus, one would have been motivated to make buffered solutions with those amounts. Further, Callahan teach buffering agents based on glycine (section 0131). Thus, one would have been motivated to use the Gly-Gly buffer (buffers at pH = 7.4+-1.0) of Mitterer (section 0047) which is taught for applications to annexin (claim 9).
One would have had a reasonable expectation of success because Consalvo teach a specific peptide (SEQ ID NO:7 (also known as UGP025) corresponds to amino acids 2-48 of human Annexin 1 where residue 24 is Leu and the polypeptide is amidated at its C-terminus (page 8 3rd complete paragraph)) and that the peptide was tested in assays (figure 8 for example). Further, Callahan recognizes a wide range of pharmacologically active peptides (section 0014 and Table 2). Callahan teach that any number of peptides may be used with the present invention (sections 0208-0247). In the instant case, 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.
In relation to the peptide as recited in claims 1, 48, 56, 57, 59 and 62-63, Consalvo teach SEQ ID NO:7 (also known as UGP025) corresponds to amino acids 2-48 of human Annexin 1 where residue 24 is Leu and the polypeptide is amidated at its C-terminus (page 8 3rd complete paragraph) which corresponds to instant SEQ ID NO:8. Since SEQ ID NO:7 of Consalvo corresponds to the elected species it is interpreted as meeting the limitation of claims 9 and 60.
In relation to the solvent as recited in claim 1bi, Consalvo teach that the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate (pages 19-20 connecting paragraph). Since Tris was used, water would have been present. It is noted that Consalvo teach that the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate (pages 19-20 connecting paragraph) where ascorbate is a carbohydrate.
In relation to the ionic strength of claims 1bii and 59b, Callahan teach the known effects of salts (sections 0147-0148) and teach that salt concentrations are used to adjust the ionic strength and are generally limited to less than 150 mM (section 0149) and recognize Na+ and Cl- as a cation and anion for salts (Table C page 17) one would have been motivated to include NaCl within such range. Further, Callahan teach that those skilled in the art will know what amount or range of components including salt can be included (section 0119). MPEP 2144.05 I recognizes that where the claimed range overlaps or lies inside ranges of the prior art a prima facie case of obviousness exists (1 micromolar to 50 mM lies inside less than 150 mM).
In relation to any carbohydrate or sugar alcohol of claims 1bi, 1bii, 24, 25, 28, 39, 57 and 64, Consalvo teach that the compositions may include typical pharmaceutical excipients, diluents or carriers such as glycerol (page 23 lines 6-14). Callahan teach that polyols include mannitol, sucrose and glycerol (section 0135) and that mannitol is a commonly used bulking agent (section 0133). Callahan recognizes a combination of stabilizers to reduce aggregation and degradation (section 0138). Callahan teach optimizing stability by focusing on the effect of sucrose and mannitol (section 0360). Thus, one would have been motivated to include sucrose and mannitol in the compositions based on their known effects. Callahan teach that those skilled in the art will know what amount or range of excipient can be included in any particular formulation (section 0119). MPEP 2144.05 I recognizes that where the claimed range overlaps or lies inside ranges of the prior art a prima facie case of obviousness exists. Callahan teach a range of amounts of the stabilizer and bulking agents (sections 0138-0139).
In relation to the pH of claims 1-2, 5, 39, 57 and 59, Consalvo teach examples with a pH of 7 ( the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate pages 19-20 connecting paragraph) and a pH of 8 (the HPLC was used for peptide purification and that separation was achieved using a linear gradient from 0% A (10 mM Tris, pH 8) to 20% B (10 mM Tris, 0.5 NaCl pH 8) page 20 lines 13-20) as well as a pH of 8.5 (page 19 last paragraph). Further, Callahan teach a pH buffering agent in a range of about 5 mM to about 20 mM with a pH range of about 3 to about 8 (section 0019). Callahan teach a buffer system and recognizes a pH range that includes 7.0, 8.0 and 8.3 (section 0128).
In relation to claims 11 and 61, Consalvo teach that the amidation was carried out at 0.5 mg/ml of the peptide (pages 19-20 connecting paragraph). Further, Consalvo teach that the effective amount will vary and includes between 10 micrograms/ml and 1000 micrograms/ml (page 23 lines 3-5 and 15-21).
In relation to claim 36, Consalvo teach examples with Tris buffer ( the amidation was carried out at 0.5 mg/ml of the peptide in the presence of 25 mM Tris pH 7 and 3 mM ascorbate pages 19-20 connecting paragraph; the HPLC was used for peptide purification and that separation was achieved using a linear gradient from 0% A (10 mM Tris, pH 8) to 20% B (10 mM Tris, 0.5 NaCl pH 8) page 20 lines 13-20).
In relation to the glycylglycine of claims 36, 39 and 57, Mitterer teach that a particularly preferred buffer is Gly-Gly (buffers at pH = 7.4+-1.0) (section 0047). Callahan teach a pH buffering agent in a range of about 5 mM to about 20 mM with a pH range of about 3 to about 8 (section 0019).
In relation to the tween (polysorbate) of claims 39 and 57, Callahan teach a known non-ionic surfactant is Tween-80 (section 0145) and teach an example where Tween was used to inhibit aggregation (sections 0358 and 0366). Callahan teach that those skilled in the art will know what amount or range of excipient can be included in any particular formulation (section 0119). Callahan teach a range of amounts of Tween (section 0145).
In relation to claim 67, Consalvo teach that the peptides were lyophilized (page 20 lines 10-12).
Response to Arguments - 103
Applicant's arguments filed 5/11/26 have been fully considered but they are not persuasive with respect to the rejections set forth above.
Although applicants argue that the claims have been amended, the amended claims are addressed above.
Although applicants argue that ascorbate is only taught in the context of certain peptides, Consalvo expressly teach SEQ ID NO:7 (also known as UGP025) corresponds to amino acids 2-48 of human Annexin 1 where residue 24 is Leu and the polypeptide is amidated at its C-terminus (page 8 3rd complete paragraph). Consalvo teach that ‘C-terminal alpha-amidation (if required) was carried out’ using rPAM and then Consalvo recites what was used on conjunction with rPAM (pages 19-20 connecting paragraph). Since SEQ ID NO:7 is amidated at its C-terminus then amidation of the C-terminus is required and would have been done via the method taught by Consalvo (pages 19-20 connecting paragraph) which contains ascorbate.
Although applicants argue about glycine-extended peptides, Consalvo teach that ‘C-terminal alpha-amidation (if required) was carried out’ using rPAM and then Consalvo recites what was used in conjunction with rPAM (pages 19-20 connecting paragraph). Thus, the method is not limited only to particular peptides but is for that in which C-terminal alpha-amidation is required. Consalvo expressly teach SEQ ID NO:7 (also known as UGP025) corresponds to amino acids 2-48 of human Annexin 1 where residue 24 is Leu and the polypeptide is amidated at its C-terminus (page 8 3rd complete paragraph).
Although applicants argue that a liquid pharmaceutical is not taught, Consalvo teach that peptides were lyophilized but the prior step (or steps) require a peptide in a liquid composition (see pages 19-20). Further, Consalvo expressly teach liquid solutions (page 23 lines 6-14).
Although applicants argue about a certain ionic strength or the presence of a carbohydrate or sugar alcohol, claim 59 does not require a carbohydrate or sugar alcohol. Claim 1b recites either option i or ii and option i does not require a specific ionic strength. The specific claim limitations are addressed in the rejection set forth above.
Although applicants argue about a safe dosage form and stability, the instant claims do not recite specifics about safety or stability. In response to applicant's argument that the references fail to show certain features of the invention, it is noted that the features upon which applicant relies (i.e., safety or stability) are not recited in the rejected claim(s). Although the claims are interpreted in light of the specification, limitations from the specification are not read into the claims. See In re Van Geuns, 988 F.2d 1181, 26 USPQ2d 1057 (Fed. Cir. 1993).
Although applicants argue that Consalvo does not teach examples with a liquid formulation, Consalvo teach that peptides were lyophilized but the prior step (or steps) require a peptide in a liquid composition (see pages 19-20). Further, Consalvo expressly teach liquid solutions (page 23 lines 6-14). Applicants own new claim 67 refers to providing a liquid formulation then lyophilizing.
Although applicants argue about the teachings of Consalvo alone, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).
Although applicants argue that Callahan refers to lyophilization, applicants own new claim 67 refers to providing a liquid formulation then lyophilizing.
Although applicants argue that one would not have been motivated to add mannitol or salt, Callahan teach that the role of formulation excipients is to provide stabilization against stresses (section 0118). Callahan teach that those skilled in the art will know what amount or range of excipient can be included in any particular formulation to achieve one that promotes retention of stability and that the amount and type of salt can be selected as well as the type of sugar (section 0119). Callahan teach that the excipients share an interdependency (section 0122). Callahan teach the known effects of salts (sections 0147-0148) and teach that salt concentrations are used to adjust the ionic strength and are generally limited to less than 150 mM (section 0149) and recognize Na+ and Cl- as a cation and anion for salts (Table C page 17). Callahan teach that mannitol is a commonly used bulking agent (section 0133).
Although applicants argue that Consalvo does not teach instability of Annexin A1 peptides, the instant claims are not drawn to methods of determining stability.
Although applicants argue about hindsight reasoning, it must be recognized that any judgment on obviousness is in a sense necessarily a reconstruction based upon hindsight reasoning. But so long as it takes into account only knowledge which was within the level of ordinary skill at the time the claimed invention was made, and does not include knowledge gleaned only from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin, 443 F.2d 1392, 170 USPQ 209 (CCPA 1971).
Double Patenting
Claims were previously rejected based on the application and references cited below. Since the claims have been amended (including the addition of a new claim), the rejections are updated to correspond to the instant claims.
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 5, 9, 11, 24-25, 28, 36, 39, 48 and 56-57 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of copending Application No. 18871530 (reference application; ‘530’). Although the claims at issue are not identical, they are not patentably distinct from each other.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
530 teach liquid pharmaceutical compositions (claim 1) specifically comprising SEQ ID NO:6 (Annexin A1 2-48 V24L) with a C-terminal amidation (claim 5). 530 teach pH ranges and recites a pH of about 8.3 (claims 8-9). 530 teach a range of amounts of the peptide including 0.5-10 mg/ml (claim 6). 530 recites the inclusion of mannitol, sucrose, polysorbate-80 and glycylglycine buffer at certain ranges (claim 15). 530 recites the inclusion of water (claim 16).
530 does not teach a specific single embodiment with the combination of elected species.
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 530 based on the specific teachings and suggestions of 530. 530 suggest specific (and a finite number of ) components (claim 15) including mannitol, sucrose, polysorbate-80 and glycylglycine (claim 15). Based on such list one would have been motivated to make compositions comprising such components. Further, 530 provides additional details about the specific peptide (claim 5). One would have had a reasonable expectation of success since methods of combining components were known. In the instant case, the claimed elements were known and one skilled in the art could have combined the elements as claimed by known methods.
In relation to the peptide as recited in claims 1, 48 and 56-57, 530 teach liquid pharmaceutical compositions (claim 1) specifically comprising SEQ ID NO:6 (Annexin A1 2-48 V24L) with a C-terminal amidation (claim 5) which corresponds to instant SEQ ID NO:8. Since SEQ ID NO:7 of Consalvo corresponds to the elected species it is interpreted as meeting the limitation of claim 9.
In relation to the solvent as recited in claim 1bi, 530 recites the inclusion of water (claim 16).
In relation to any carbohydrate or sugar alcohol of claims 1bi, 24, 25 and 28, 530 recites the inclusion of mannitol and sucrose at certain ranges (claim 15). MPEP 2144.05 I recognizes that where the claimed range overlaps or lies inside ranges of the prior art a prima facie case of obviousness exists.
In relation to the pH and buffer of claims 1-2, 5 and 36, 530 teach pH ranges and recites a pH of about 8.3 (claims 8-9) and recites the inclusion of glycylglycine buffer at certain ranges (claim 15).
In relation to claim 11, 530 teach a range of amounts of the peptide including 0.5-10 mg/ml (claim 6).
In relation to claims 39 and 57, 530 recites the inclusion of mannitol, sucrose, polysorbate-80 and glycylglycine buffer at certain ranges (claim 15).
Claims 1-2, 5, 9, 11, 24-25, 28, 36, 39, 48, 56-57, 59-64 and 67 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-32 of copending Application No. 18871530 (reference application; ‘530’) in view of Callahan et al. (US 2009/0258017; ‘Callahan’).
This is a provisional nonstatutory double patenting rejection.
530 teach liquid pharmaceutical compositions (claim 1) specifically comprising SEQ ID NO:6 (Annexin A1 2-48 V24L) with a C-terminal amidation (claim 5). 530 teach pH ranges and recites a pH of about 8.3 (claims 8-9). 530 teach a range of amounts of the peptide including 0.5-10 mg/ml (claim 6). 530 recites the inclusion of mannitol, sucrose, polysorbate-80 and glycylglycine buffer at certain ranges (claim 15). 530 recites the inclusion of water (claim 16).
530 does not teach an ionic strength range or a specific single embodiment with the combination of elected species.
Callahan teach that purified peptides are only marginally stable in an aqueous state and undergo chemical and physical degradation during processing and storage (section 0016). Callahan teach that a lyophilized formulation usually comprises a buffer, a bulking agent and a stabilizer and the various components have particular functions (section 0117 and Table A). Callahan teach that the role of formulation excipients is to provide stabilization against stresses (section 0118). Callahan teach that those skilled in the art will know what amount or range of excipient can be included in any particular formulation to achieve one that promotes retention of stability and that the amount and type of salt can be selected as well as the type of sugar (section 0119). Callahan teach that the excipients share an interdependency (section 0122). Callahan teach the known effects of salts (sections 0147-0148) and teach that salt concentrations are used to adjust the ionic strength and are generally limited to less than 150 mM (section 0149) and recognize Na+ and Cl- as a cation and anion for salts (Table C page 17). Callahan recognizes a wide range of pharmacologically active peptides (section 0014 and Table 2). Callahan teach that any number of peptides may be used with the present invention (sections 0208-0247). Callahan teach lyophilized formulations (title and abstract and section 0112-0114).
It would have been obvious to one of ordinary skill in the art before the effective filing date to modify the teachings of 530 based on the specific teachings and suggestions of 530. 530 suggest specific (and a finite number of ) components (claim 15) including mannitol, sucrose, polysorbate-80 and glycylglycine (claim 15). Based on such list one would have been motivated to make compositions comprising such components. Further, 530 provides additional details about the specific peptide (claim 5). Since Callahan teach that purified peptides are only marginally stable in an aqueous state and undergo chemical and physical degradation during processing and storage (section 0016) one would have been motivated to incorporate the teachings of Callahan. Callahan teach that those skilled in the art will know what amount or range of excipient can be included in any particular formulation to achieve one that promotes retention of stability and that the amount and type of salt can be selected as well as the type of sugar (section 0119). Callahan teach that the excipients share an interdependency (section 0122). Callahan teach the known effects of salts (sections 0147-0148) and teach that salt concentrations are used to adjust the ionic strength and are generally limited to less than 150 mM (section 0149) and recognize Na+ and Cl- as a cation and anion for salts (Table C page 17). Thus one would have been motivated to include NaCl in such amounts. One would have had a reasonable expectation of success since methods of combining components were known. Further, Callahan recognizes a wide range of pharmacologically active peptides (section 0014 and Table 2) and teach that any number of peptides may be used with the present invention (sections 0208-0247). In the instant case, the claimed elements were known and one skilled in the art could have combined the elements as claimed by known methods.
In relation to the peptide as recited in claims 1, 48, 56-57, 59 and 62-63, 530 teach liquid pharmaceutical compositions (claim 1) specifically comprising SEQ ID NO:6 (Annexin A1 2-48 V24L) with a C-terminal amidation (claim 5) which corresponds to instant SEQ ID NO:8. Since SEQ ID NO:7 of Consalvo corresponds to the elected species it is interpreted as meeting the limitation of claims 9 and 61.
In relation to the solvent as recited in claim 1bi and 59b, 530 recites the inclusion of water (claim 16).
In relation to the ionic strength of claims 1bii and 59b, Callahan teach the known effects of salts (sections 0147-0148) and teach that salt concentrations are used to adjust the ionic strength and are generally limited to less than 150 mM (section 0149) and recognize Na+ and Cl- as a cation and anion for salts (Table C page 17) one would have been motivated to include NaCl within such range. Further, Callahan teach that those skilled in the art will know what amount or range of components including salt can be included (section 0119).
In relation to any carbohydrate or sugar alcohol of claims 1bi, 24, 25, 28 and 64, 530 recites the inclusion of mannitol and sucrose at certain ranges (claim 15). MPEP 2144.05 I recognizes that where the claimed range overlaps or lies inside ranges of the prior art a prima facie case of obviousness exists.
In relation to the pH and buffer of claims 1-2, 5, 36 and 59, 530 teach pH ranges and recites a pH of about 8.3 (claims 8-9) and recites the inclusion of glycylglycine buffer at certain ranges (claim 15).
In relation to claims 11 and 61, 530 teach a range of amounts of the peptide including 0.5-10 mg/ml (claim 6).
In relation to claims 39 and 57, 530 recites the inclusion of mannitol, sucrose, polysorbate-80 and glycylglycine buffer at certain ranges (claim 15).
In relation to claim 67, Callahan teach lyophilized formulations (title and abstract and section 0112-0114).
Response to Arguments – Double Patenting
Applicant's arguments filed 5/11/26 have been fully considered but they are not persuasive with respect to the rejections set forth above.
Although applicants argue that the claims have been amended, the amended claims are addressed above.
Conclusion
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RONALD T NIEBAUER whose telephone number is (571)270-3059. The examiner can normally be reached M - F 6:30 - 2:30 EST.
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RONALD T. NIEBAUER
Primary Examiner
Art Unit 1658
/RONALD T NIEBAUER/Examiner, Art Unit 1658
Prosecution Insights