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 .
Priority
The instant application, filed on 15 April, 2024, is a 371 of PCT/EP2022/065901, filed on 10 June 2022.
Acknowledgment is made of applicant’s claim for foreign priority under 35 U.S.C. 119 (a)-(d) to EP 21180388.7, filed on 18 June, 2021. Receipt is acknowledged of certified copies of papers required by 37 CFR 1.55.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 15 April, 2024 has been considered by the examiner.
Status of Application, Amendments, and/or Claims
The response filed on 15 April, 2024 has been entered in full. These are the amended claims of the original claim set received on 15 April, 2024. In the amendment, claims 4-6 are amended and claims 1-3 and 7-10 are original. Therefore, claims 1-10 are pending and are the subject of this Office Action.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency - The Incorporation by Reference paragraph required by 37 CFR 1.821(c)(1) is missing or incomplete. See item 1) a) or 1) b) above.
Required response – Applicant must provide:
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required incorporation-by-reference paragraph, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Claim Objections
Claims 5, 9, and 10 and objected to because of the following informalities:
The claims state “which” in instances where “wherein” is necessary.
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.
Claims 2, 5, 7, and 10 are rejected under 35 U.S.C. 112(b), as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor, regards as the invention.
Regarding claims 2, 5, 7, and 10, the phrase "preferably" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d). For the purpose of further examination, the claims will be interpreted such that the recitations after preferably are optional limitations.
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 9 and 10 are rejected under 35 U.S.C. 101 because the claimed invention is directed to Judicial exceptions (i.e. a law of nature, natural phenomenon, and/or an abstract idea) without significantly more.
Regarding claim 9 for step 2A, prong 1, the judicial exceptions (JEs) are:
1. The relationship between level of GPVI and a medical condition that will receive treatment (i.e., a natural correlation),
2. “Determining” GPVI concentration in a patient (i.e., a mental step).
It is noted that when looking up the meaning for “determining” GPVI concentration, the specification does not provide a definition of “determining,” but provides examples, see page 42 regarding ELISA and computer-implemented method. Regarding the computer-implemented method, the method uses a computer to identify patients who have a certain concentration of GPVI. This is a mental step and thus a JE. Regarding “determining” in the context of running an ELISA assay, see analysis for Step 2B.
For step 2A, prong 2, integration into a practical application, claim 9 recites no integration into a practical application. Claim 9 recites that the patient with a certain level of GPVI is selected, but there is no integration of the natural correlation (GPVI level to medical condition) to a practical application.
For step 2B, where claim 9 amounts to significantly more than the JE, the spec has indicated that “determining” GPVI, using an assay to identify an amount of PGVI, can be achieved with ELISA assays. According to the spec, ELISA assays are routine in the art. See also Bigalke (103 below). Because ELISA assays are well-understood, routine and conventional, “determining” in claim 9 does not take the claim out of 101.
Regarding claim 10, the claim is interpreted as the selection criteria for patients selected for testing with the diagnostic assay, and prior diagnostics are needed to screen for the condition identified by the assay.
This still falls under step 2A, prong 1 reciting of a JE as outlined above.
For step 2A, prong 2, integration into a practical application, claim 10 recites no integration into a practical application. Claim 10 recites further limitations for the criteria for patient selection, but does not integrate the natural correlation of GPVI level to medical condition into a practical application.
For step 2B, where claim 10 amounts to significantly more than the JE, the spec has indicated testing for bleeding complication before invasive procedures in vulnerable patients is routine in the art, with a variety of guidelines and test, further Munoz et al. (2016) Pre-operative haematological assessments in patients schedules for major surgery Anaesthesia 71 (Suppl. 1) 19-28, teaches pre-operative testing for blood disorders which could lead to bleeding complications in vulnerable patients is important in avoiding post operative morbidity and mortality due to the complications. Because prior screening in vulnerable patients is well-understood, routine, and conventional, “patient to be treated with percutaneous intervention or surgery” in claim 10 does not take the claim out of 101.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Gador (2017, of record IDS 04/15/2024, NPL No: 3) as evidenced by Munch et al. (US 8,119,135) and in view of Gervasi et al. (2018) Parenteral protein formulations: An overview of approved products within the European Union European Journal of Pharmaceutics and Biopharmaceutics 131; 8-24 (hereafter Gervasi) and Akers (2002) Excipient-Drug Interactions in Parenteral Formulations Journal of Pharmaceutical Science 91 (11); 2283-2300.
In regards to claim 1 Gador teaches a formulation of the collagen binding-dimeric fusion protein PR-15 For parenteral administration (pg.13, lines 3-6). PR-15 is 99% sequence identity to SEQ ID NO: 1 of the instant application as evidenced by Munch et al. which recites the amino acid sequence for PR-15 is SEQ ID NO: 147 of the patent and further is shown in figure 7 (Col 27, lines 33-35). Alignment of the two sequences is shown below.
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Further, Gador teaches formulations comprising approximately 2.5 mg/mL of the fusion protein, 4% mannitol, and 1% saccharose, and further wherein the buffer is Histidine (His/Hcl) with a pH 7 (with a pH adjusting agent as needed) (pg.32, lines 1-12 / Table 7).
In regards to claims 2 and 3 teaches the addition of the detergent Tween 20 and further demonstrates formulations with 0.05% Tween 20 (Table 7 and Table 8).
In regards to claim 4 and 5 Gador teaches that the formulation is an injectable formulation (aqueous dispersion) (pg.143, lines 16-17) and demonstrates stability at 25 °C and 40 °C under accelerated degradation conditions (Figures 7, 9, 10, and 11). Gador further teaches the use of Histidine buffer improves thermal stability and suggest that long term stability studies of PR-15 formulations at 5 °C ± 3 °C for at least a year or at 25 °C ± 2 °C for at least 6 months (pg.145, lines 13-16)
Gador fails to teach the 10mM concentration of His/Hcl and the 2.5 percent saccharose of claim 1, and the lyophilized composition of claim 5.
Gervasi, however in regards to claim 1 teaches the amino acid excipient such as Histidine (which is the most commonly used amino acid excipient) play several roles in parenteral formulations such as buffers, stabilizers or bulking agents based on their concentrations (pg.13, col 1, lines 2-6), for the excipient Histidine excipient high concentrations acting as stabilizers or bulking agents and low concentration acting as buffers (pg.13, col 2, lines 13-14). Gervasi also provides examples of approved protein therapeutic which use 10mM Histidine/Hcl such as ranibizumab (pg.21 Table 3).
Further, Gervasi in regards to claims 1 and 5 teaches sucrose (saccharose) is the most commonly used excipient as a bulking and stabilizing agent in both liquid and lyophilized formulations, and sucrose is a cryo/lyo-protective agent for protein formulations as it can maintain it amorphous state during lyophilization (pg.14, col 1, lines 38-39/ pg.14, col 2, lines 10-13). Gervasi also teaches combinations of sucrose and mannitol can be used with sucrose as a stabilizer and mannitol as a bilking agent (pg.15, col 1, lines 9-13). Gervasi is silent on the effect of concentration of sucrose on formulation properties, however, Akers teaches the ratio between sucrose and the protein is important in inhibiting sucrose crystallization minimizing the moisture content, and decreasing the glass transition temperature during storage (pg.2292, col 2, lines 13-18).
In regards to claim Claims 6 and 7, the claims are recited towards the pharmaceutical composition itself and not a method of use of the pharmaceutical composition, therefore, the recitation of “for use in treatment” of claim 6 and the subsequent limitation of the patient in claim 7 are intended uses of the pharmaceutical composition and do not impart any further structural limitations on the claimed composition, thus do not have significant patentable weight (See MPEP 2111.02(II)).
Thus, Gador discloses formulations of a collagen-binding dimeric fusion protein with a 99% sequence identity to SEQ ID NO:1 of the instant application wherein the concentration of the fusion protein has a concentration more than 2.4 mg/mL in Histidine buffer with 4% mannitol and 1% sucrose, at a pH 7 and further comprising a Tween 20 detergent, further Gador give temperature guidelines for stability. Gervasi and Akers teach selections such as buffer choice, buffer concentration, and stabilizer choice and mass ratio impact the formulations stability and further allows for it to be protected during lyophilization. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of Gador informed with the teachings of Gervasi and Akers, to routinely optimize (See MPEP 2144.05 (II)) the excipients selected for the parenteral formulation to meet the industry suggested stability and temperature guidelines and obtain an stable aqueous or lyophilized pharmaceutical composition for commercial use with a reasonable expectation of success.
Claim 8, 9, and 10 is rejected under 35 U.S.C. 103 as being unpatentable over Gador in view of Gervasi and Akers as applied to claim 1 above, and further in view of Bigalke et al. (2011) Sandwich Immunoassay for Soluble Glycoprotein VI in Patients with Symptomatic Coronary Artery Disease Clinical Chemistry 57:6; 898-904 (hereafter Bigalke).
Claim 8 is drawn to a kit comprising the pharmaceutical composition of claim 1 and a diagnostic antibody directed against soluble glycoprotein VI. The kit does not add any further structural limitation of the pharmaceutical composition of claim one and is therefore taught by Gador in view of Gervasi and Akers as outlined above. Gador in view of Gervasi and Akers fails to teach the diagnostic antibody to detect GPVI of claims 8, and 9, and the computer implemented method of claim 10.
Bigalke, however, teaches using antibodies for glycoprotein VI in a bead based sandwich immunoassay to identify patient with acute coronary syndrome earlier than other laboratory markers (pg.898, col 1, lines 7-9 / pg.898, col 2, lines 3-5).
In regards to claim 10 Bigalke teaches using a luminex (instrument for measuring controlled by a software / computer implemented method) to determine the concentration sGVPI (pg.899, col 2, lines 40-43).
Thus, Gador in view of Gervasi and Akers discloses a pharmaceutical composition comprising a dimeric fusion protein comprising the extracellular domain of glycoprotein VI, and Bigalke teaches using antibodies against glycoprotein VI to detect acute coronary syndrome earlier than other markers. Therefore, a person of ordinary skill in the art before the effective filing date of the claimed invention would have found it obvious to combine the teachings of Gador in view of Gervasi and Akers with the teachings of Bigalke with a reasonable expectation of success to develop a kit in which both a treatment and diagnostic method are included for clinical use wherein the diagnostic method comprises a antibody to detect GPVI for a diagnostic method with an software controlled measuring system wherein the method has increased sensitivity.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DASIA A ALDARONDO whose telephone number is (571)272-1977. The examiner can normally be reached on Monday – Friday from 8:30am to 4:30pm.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Joanne Hama, can be reached at telephone number (571)272-2911. The fax phone number for the organization where this application or proceeding is assigned is (571)273-8300.
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/D.A.A/Examiner, Art Unit 1647 /JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
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