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
Applicant's election with traverse of Group 1 in the reply filed on 12/9/25 is acknowledged. The traversal is on the ground(s) that the references individually do not anticipate all of the claim limitations and that there is not a teaching of low ionic strength. This is not found persuasive because MPEP 1850 II 2nd paragraph recognizes that a contribution over the prior art should be considered with respect to novelty and inventive step. Further, the 102 and 103 rejections below address in detail the claim limitations. With respect to low ionic strength, claim 1bi merely recites water and does not require a specific ionic strength.
The requirement is still deemed proper and is therefore made FINAL.
Applicant’s election of the species of SEQ ID NO:8, mannitol, glycylglycine and polysorbate-80 in the reply filed on 12/9/25 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claim 58 is withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention, there being no allowable generic or linking claim.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.
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.
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 and 59-64 are being examined.
Priority
The priority information is found in the filing receipt dated 10/12/23.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/9/25, 10/1/25 and 5/12/23 have been considered by the examiner.
Specification
The disclosure is objected to because of the following informalities: at many locations throughout the specification (page 3 lines 9, 18, 19, specifically ‘7,3’, ‘6,5’ and ‘2,5’ and many other locations) commas are used where the use of a comma does not seem appropriate. Page 5 line 4 is evidence that numbers that include decimals are shown by the use of a period.
On page 51, the line numbering on the left hash is missing ‘15’ and ‘20’ which appear to have been moved toward the center of the row.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
Claims 1-2, 5, 9, 11, 24-25, 28, 36, 39, 48, 56-57 and 60-62 are 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 1b refers to a solvent that is selected from i and ii. The 3rd to last line of claim 1 recites ‘wherein said solvent…’. Such wherein clause is included with option ii. It is unclear if the wherein clause is to be applied to both options i and ii (it does refer to ‘said solvent’) or only option ii (it is specifically recited with option ii). As such, there is more than one reasonable interpretation of the claim. Dependent claims 2, 5, 9, 11, 36, 48 and 56 do not clarify the claim scope.
Claim 1 line 1 recites ‘6,0’. Claim 5 recites ‘8,5’. Claim 9 recites ‘0,1’. Claim 28 recites ‘0,5’. Claim 39 recites ‘0,01’ and ‘8,3’. Claim 57 recites ‘8,2’, ‘8,4’ and ‘0,5’. Claim 60 recites ‘0,1’. Claim 61 recites ‘0,1’. The use of a comma at these locations does not seem appropriate. Page 5 line 4 of the specification is evidence that numbers that include decimals are shown by the use of a period. In the instant case, it is not clear if the commas are intended to be periods or dashes (to represent a range) or if they are extraneous. None of the dependent claims clarify the claim scope.
The term “approx..” in claim 39 (used 5 times) is a relative term which renders the claim indefinite. The term “approx.” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. In the instant case, the upper and lower limits that are acceptable are unclear.
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.
Claim 36 last line contains the trademark/trade name Tween. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a product and, accordingly, the identification/description is indefinite.
Although unclear, the claims have been given the broadest reasonable interpretation consistent with the specification.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claims 56 and 63 are rejected 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.
Claim 56 depends on claim 48 which recites ‘NH2’ at the C-terminal end of the sequence. Thus, claim 56 is reciting a feature that is already necessarily present in claim 48.
Claim 63 depends on claim 62 which recites ‘NH2’ at the C-terminal end of the sequence. Thus, claim 63 is reciting a feature that is already necessarily present in claim 62.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1-2, 5, 9, 11, 24-25, 28, 36, 39, 59-61 and 64 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
“To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that “the inventor invented the claimed invention.” Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) (“[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed.”). Thus, an applicant complies with the written description requirement “by describing the invention, with all its claimed limitations, not that which makes it obvious,” and by using “such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention.” Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966.” Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the Application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
Further, to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include: a) the scope of the invention; b) actual reduction to practice; c) disclosure of drawings or structural chemical formulas; d) relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation; e) method of making the claimed compounds; f) level of skill and knowledge in the art; and g) predictability in the art.
(1) Scope of the invention/Partial structure/disclosure of drawings:
Claims 1 and 59 refer to ‘variant of any one of SEQ ID NOs:4-9 comprising 1 to 6 individual amino acid substitutions, wherein said variant is a ligand and/or agonist of one or more of Formyl Peptide Receptor 1 (FPR1), Formyl Peptide Receptor 2 (FPR2) and Formyl Peptide Receptor 3 (FPR3)’.
When 6 of the positions of any of the peptides are varied to any of the 20 common amino acids there are at least 206 (i.e. 64000000) different possible sequences. As such, the genus is large.
The sequence listing only includes 11 total sequences and the examples appear to be limited to a single or only a few peptides (page 47 first paragraph refers to AnxA1).
Instant claims 48, 56-57 and 62-63 are limited to a specific peptide and are not included in the instant rejection.
(2) Level of skill and knowledge in the art/predictability in the art:
The level of skill in the art is high.
Claims 1 and 59 refer to ‘variant of any one of SEQ ID NOs:4-9 comprising 1 to 6 individual amino acid substitutions, wherein said variant is a ligand and/or agonist of one or more of Formyl Peptide Receptor 1 (FPR1), Formyl Peptide Receptor 2 (FPR2) and Formyl Peptide Receptor 3 (FPR3)’.
With respect such activity, no specific direction is provided as to which residues of the peptide are responsible for such activity and which amino acids can be substituted while retaining the activity.
(3) Physical and/or chemical properties and (4) Functional characteristics:
Claims 1 and 59 refer to ‘variant of any one of SEQ ID NOs:4-9 comprising 1 to 6 individual amino acid substitutions, wherein said variant is a ligand and/or agonist of one or more of Formyl Peptide Receptor 1 (FPR1), Formyl Peptide Receptor 2 (FPR2) and Formyl Peptide Receptor 3 (FPR3)’. When 6 of the positions of any of the peptides are varied to any of the 20 common amino acids there are at least 206 (i.e. 64000000) different possible sequences. The elected species is 47 amino acids in length. Substituting at 6 positions allows 13% of the sequence to be modified.
There is no adequate disclosed correlation between structure and function particularly related to what structures are adequate to result in the functions as recited in the claims specifically for the many possible substitutions. Although claims 1 and 59 refer to Formyl Peptide Receptor 1 (FPR1), Formyl Peptide Receptor 2 (FPR2) and Formyl Peptide Receptor 3 (FPR3) there does not appear to be any binding data for such receptors. One of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus and that there is a lack of the predictability in the art and that the applicant was not in possession of the claimed genus.
(5) Method of making the claimed invention/actual reduction to practice:
The specification examples beginning at page 47 appear to relate to a single peptide (AnxA1). Mere synthesis of a peptide does not show that it would have the functionalities claimed nor does synthesis allow one to know which amino acids can be substituted while retaining the claimed function.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”) Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the entire scope of the claimed invention.
Claim Rejections - 35 USC § 101
35 U.S.C. 101 reads as follows:
Whoever invents or discovers any new and useful process, machine, manufacture, or composition of matter, or any new and useful improvement thereof, may obtain a patent therefor, subject to the conditions and requirements of this title.
Claims 1-2, 5, 9, 11, 24-25, 28, 36, 59-61 and 64 are rejected under 35 U.S.C. 101 because the claimed invention is directed to a natural phenomenon (product of nature) without significantly more. The claim(s) recite(s) peptides/compositions which correspond to products of nature. This judicial exception is not integrated into a practical application because there is no additional elements that apply or use the judicial exception. The claim(s) does/do not include additional elements that are sufficient to amount to significantly more than the judicial exception as discussed below.
This 101 rejection is consistent with the most recent training provided by the office which will be referred to as 'guidance' (see MPEP 2106).
In comparison to the subject matter eligibility test as set forth in the guidance, the claims are drawn to compositions. Thus the answer to step 1 is yes.
The instant specification (page 45) recites the full length human Annexin A1 sequence. Instant SEQ ID NOs: 4-6 correspond to fragments of the full length human sequence.
In relation to prong one of step 2a of the guidance the answer is yes because the peptides correspond to fragments of a protein (i.e. products of nature which are a natural phenomenon).
With respect to additional elements, claim 1b recites water as a solvent which itself is naturally occurring. Claim 24 recites disaccharides which are naturally occurring. Claims 25 and 28 recite mannitol and sucrose which are naturally occurring. Claim 36 recites amino acids and lysine which are naturally occurring.
Instant claims 48, 56-57 and 62-63 are not included in the instant rejection since they require a peptide that has been modified from the naturally occurring sequence (V24L). Instant claim 39 is not included in the instant rejection since it has been interpreted as requiring polysorbate 80 which is not naturally occurring.
The instantly claimed compositions are like the novel bacterial mixture of Funk Brothers which contained multiple naturally occurring components, which was held ineligible because each species of bacteria in the mixture (like each component in the peptide composition) continued to have “the same effect it always had”, i.e., it lacked markedly different characteristics. Funk Brothers Seed Co. v. Kalo Inoculant Co., 333 U.S. 127, 131 (1948), discussed in Myriad Genetics, 133 S. Ct. at 2117 (explaining that the bacterial mixture of Funk Brothers “was not patent eligible because the patent holder did not alter the bacteria in any way”).
In relation to prong two of step 2a, the instant rejected claims are product claims and do not require any additional elements that apply the judicial exception in a manner that imposes a meaningful limit on the judicial exception. Thus the answer to prong two of step 2a is no.
The instant claims recite SEQ ID NOs:4-6 which are fragments of a known protein. The Myriad Supreme Court decision (Association for Molecular Pathology v. Myriad Genetics, 569 U.S. 12-398 (2013)) stated: “Myriad’s claims are not saved by the fact that isolating DNA from the human genome severs the chemical bonds that bind gene molecules together” (page 2 and 14). In the instant case, applicants’ claims are not saved by the fact that the peptides of the instant claims correspond to fragments (the protein with severed bonds).
Further, there is no evidence of any markedly different characteristic. MPEP 2106.04(c) II C recognizes that a change cannot be an inherent or innate characteristic on the naturally occurring counterpart or an incidental change in a characteristic of the naturally occurring counterpart. Thus the answer to step 2b is no because there is not adequate evidence to conclude that the claims include significantly more than the judicial exception.
Claim Rejections - 35 USC § 102
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 and 62-63 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).
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. As discussed above, claim 1 is unclear with respect to the wherein clause. One interpretation is that the wherein clause only applies for option 1bii. 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).
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.
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 and 59-64 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 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. As discussed above, claim 1 is unclear with respect to the wherein clause. One interpretation is that the wherein clause only applies for option 1bii. 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 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).
Claim(s) 1-2, 5, 9, 11, 24-25, 28, 36, 39, 48, 56-57 and 59-64 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 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. As discussed above, claim 1 is unclear with respect to the wherein clause. One interpretation is that the wherein clause only applies for option 1bii. 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 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 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).
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-2, 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). One interpretation is that the wherein clause only applies for option 1bii.
In relation to any carbohydrate or sugar alcohol of claims 1bii, 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 and 59-64 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).
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). One interpretation is that the wherein clause only applies for option 1bii.
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 1bii, 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).
Conclusion
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