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
This application filed 03/13/2024 is a National Stage entry of PCT/CN2022/118429 , International Filing Date: 09/13/2022 claims foreign priority to 202111126033.7, filed 09/24/2021.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 03/13/2024 and 11/10/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
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 – Nucleotide and/or amino acid sequences appearing in the specification are not identified by sequence identifiers in accordance with 37 CFR 1.821(d).
1. The specification filed on 03/13/2024 does not recite appropriate sequence identifiers in the form of
SEQ ID numbers. For example, please see: page 4, line 8; page 9, [0021]; [0022].
The sequences recited in the specification must include SEQ ID numbers to properly identify the
sequences. Appropriate correction is required.
2. The claims filed on 03/13/2024 do not recite appropriate sequence identifiers in the form of SEQ ID
numbers. The sequences recited in the claims must include SEQ ID numbers to properly identify the
sequences. For example, an appropriate form of the sequence “His-Gly-Glu-Gly-Tlir-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gn-Me-il-Glu-Glu-Ala-Val-Arg-Let-Phe-Ile-Glu-Trp-Leu-Lys-Aan-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Cys” of claim 1 is “His-Gly-Glu-Gly-Tlir-Phe-Thr-Ser-Asp-Leu-Ser-Lys-Gn-Me-il-Glu-Glu-Ala-Val-Arg-Let-Phe-Ile-Glu-Trp-Leu-Lys-Aan-Gly-Gly-Pro-Ser-Ser-Gly-Ala-Pro-Pro-Pro-Cys (SEQ ID NO: 1).” Appropriate correction is required.
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 sequence identifiers, 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 Status
The claim listing filed 03/13/2024 is pending. Claims 1, 3, 4, 5, 6, 7, 8, 9, 10
are currently amended. Claims 11-20 are new. Claims 1-20 are pending and under examination.
Claim Objections
Claim 1 is objected to because of the following informalities: amino acid sequence in line 4 is missing a SEQ ID number. Appropriate correction is required.
Claim 6 is objected to because of the following informalities: Examiner respectfully requests correcting ‘counting in’ in line 3 for grammatical correctness.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-6 and 9-17 are rejected under 35 U.S.C. 102(a)(1) and 35 U.S.C. 102(a)(2) as being anticipated by Micheal M. Xu et al., hereinafter Xu (Micheal M. Xu et al., US8,575,097B2, Date of Patent: Nov. 5, 2013).
The applied reference has a common Applicant and Inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Regarding claim 1, Xu teaches PEGylated exenatide variant (SEQ ID NO: 7-page 31) in Example 3f (page 40, 1st paragraph), wherein the PEG has a molecular weight of 20 kDa (see Example 3f, line 3) (i.e. 5-100 kDa), pH 4.5 (Example 3f, 2nd paragraph, line 2) (i.e. pH 2.0 to 6.0) and buffer comprising sodium acetate (Example 3f, 2nd paragraph, line 6) (i.e. acetic acid/sodium acetate).
Regarding claim 2, Xu teaches solvent or acceptable diluent in the aseptic formulation for injection (see page 35, column 19, last two lines).
Regarding claim 3, Xu teaches pH 4.5 (Example 3f, 2nd paragraph, line 2) (i.e. pH 3.5 to 5.5).
Regarding claim 4, Xu teaches buffer comprising sodium acetate (Example 3f, 2nd paragraph, line 6) (i.e. acetic acid/sodium acetate). Xu teaches that suitable buffer comprises acetate, citrate, borate, phosphate (see page 35, Col 19, 4th paragraph, last 2 lines).
Regarding claim 5, Xu teaches buffer comprising sodium acetate (Example 3f, 2nd paragraph, line 6) (i.e. acetic acid/sodium acetate).
Regarding claim 6, Xu teaches 0.20 mg/ml-5 mg/ml Extendin variant (i.e. peptide) (see page 36, Col 21, line 4) (i.e. 0.1-5.0 mg/ml).
Regarding claim 9, Xu teaches injection (see Example 16, line 11).
Regarding claim 10, Xu teaches administering the composition to Male Kunming mice (body weight was 22-26 g) and ascertaining hypoglycemic effects (i.e. treating) (see Example 16). Xu teaches in Example 19, Male Kunming mice (body weight was 24-30 g) randomly distributed into four groups
with six mice in each group. PB-105 (10 μg/kg), PEGylated (PEG20000) conjugate of PB-105 (PB-106) (10 μg/kg), PB-111 (10 μg/kg) and PEGylated (PEG20000) conjugate of PB-111 (PB-112) (10 μg/kg) were subcutaneously injected in bolus. PB-111 is PB-105 derivative in which cysteine at position 39 of C-terminal linked to tyrosine (i.e. SEQ ID NO: 1 in the instant application).
Embodiments of the specification disclose ‘preventing or treating’ to encompass administering to a patient who already has the disease in an amount sufficient to cure or at least partially suppress the symptoms and complications of the disease [0063].
Regarding claim 11, Xu teaches, PEG has a molecular weight of 20 kDa (see Example 3f, line 3) (i.e. 20-29 kDa).
Regarding claim 12, Xu teaches acetate, citrate, phosphate (see page 35, Col 19, 4th paragraph, last 2 lines).
Regarding claim 13, Xu teaches citrate (see page 35, Col 19, 4th paragraph, last 2 lines).
Regarding claim 14, Xu teaches lactate (see page 36, Col 22, 3rd paragraph, line 12).
Regarding claim 15, Xu teaches lactate(see page 36, Col 22, 3rd paragraph, line 12).
Regarding claim 16, Xu teaches 0.20 mg/ml-5 mg/ml Extendin variant (i.e. peptide) (see page 36, Col 21, line 4) (i.e. 0.25-1.5 mg/ml).
Regarding claim 17, Xu teaches 0.20 mg/ml-5 mg/ml Extendin variant (i.e. peptide) (see page 36, Col 21, line 4) (i.e. 0.5 mg/ml).
Claim Rejections - 35 USC § 103
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claims 1-6, 8-17, 19 and 20are rejected under 35 U.S.C. 103 as being obvious over Micheal M. Xu et al., hereinafter Xu (Micheal M. Xu et al., US8,575,097B2, Date of Patent: Nov. 5, 2013) in view of Surinder M. Singh et al., hereinafter Singh (Surinder M. Singh et al., Mechanisms of m-cresol induced protein aggregation studied using a model protein cytochrome c, J Pharm Sci, 2011; 100(5): 1679-1689).
The applied reference has a common Applicant and inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2) and 35 U.S.C. 102(a)(1).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
The teachings of Xu have been set forth above. Additionally, regarding claim 8, Xu teaches m-cresol, benzyl alcohol, methyl p-hydroxybenzoateparabens (page 36, Col 22, 2nd paragraph, line 6) (i.e. bacteriostat).
Xu does not teach 0.1-5 mg/ml.
Singh teaches that protein formulations that contain Aps (active pharmaceutical) are critical for many therapeutic and vaccine applications. Preservatives are also required for drug delivery systems such as injection pens that are used in multiple doses. Specifically, Singh teaches that m-cresol (CR) is an effective AP and is used at low levels (0.3%) in peptide and protein formulations (i.e. 3 mg/ml) (see Introduction, 2nd paragraph, 1st line).
Obviousness can be established by combining or modifying the teachings of the prior art to
produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the
motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to use the concentration of m-cresol in Singh.
Thus, one would have recognized that applying the teaching of Xu to the
teaching of Singh would have yielded predictable results as both references teach m-cresol in pharmaceutical compositions and for role of m-cresol in reducing protein aggregation (see Abstract). See MPEP §2143.
Regarding claim 19, the obviousness rationale has been set forth above. Xu teaches m-Cresol (page 36, Col 22, 2nd paragraph, line 6).
Regarding claim 20, the obviousness rationale has been set forth in the teachings of Xu and Singh. Regarding the limitation 2.0-2.5 mg/ml, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See §2144.05.
Claims 1-7 and 9-18 are rejected under 35 U.S.C. 103 as being obvious over Micheal M. Xu et al., hereinafter Xu (Micheal M. Xu et al., US8,575,097B2, Date of Patent: Nov. 5, 2013) in view of H. Leonhard Ohrem et al., hereinafter Ohrem (H. Leonhard Ohrem et al., Why is mannitol becoming more and more popular as a pharmaceutical excipient in solid dosage forms? Pharm Dev Technol, 2014; 19(3): 257–262)
The teachings of Xu have been set forth above. Additionally, regarding claim 7, Xu teaches isotonic agents mannitol, sodium chloride, glycerol (see page 36, Col 22, 3rd paragraph, 4th line).
Xu does not teach osmotic pressure regulator is 5-100 mg/ml
Ohrem teaches that mannitol excels regarding its physicochemical characteristics such as a low hygroscopicity, a strong inertness towards both the active pharmaceutical ingredient and the patient’s body (see Abstract). Ohrem specifically teaches that pharmacopoeias have set limits of 0.2% and 0.3% for sorbitol and mannitol, respectively. This reflects also the regular levels in marketed excipients.
Obviousness can be established by combining or modifying the teachings of the prior art to
produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the
motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to use a concentration of mannitol in the composition that Ohrem teaches. Xu teaches in Example 3f that PB-111 is dissolved in 1 ml buffer (line 1 in the example), the sample diluted 5-fold (line 1 in the 2nd paragraph) and after loading the column, balanced by 5-fold column volume and column balanced by 2-fold column volume. Considering the experimental steps in Ohrem, mannitol concentration would be a range from 3 mg/ml to 15 mg/ml to 30 mg/ml to 60 mg/ml.
Thus, one would have recognized that applying the teaching of Xu to the
teaching of Ohrem would have yielded predictable results as both references teach mannitol in pharmaceutical compositions and for role of mannitol strong as demonstrating inertness towards both the active pharmaceutical ingredient and the patient’s body (see Abstract). See MPEP
§2143.
Regarding claim 18, the teachings of Xu have been set forth above.
Xu teaches mannitol (see page 36, Col 22, 3rd paragraph, 4th line).
Xu does not teach 40-50 mg/ml mannitol.
Ohrem teaches that mannitol excels regarding its physicochemical characteristics such as a low hygroscopicity, a strong inertness towards both the active pharmaceutical ingredient and the patient’s body (see Abstract). Ohrem specifically teaches that pharmacopoeias have set limits of 0.2% and 0.3% for sorbitol and mannitol, respectively. This reflects also the regular levels in marketed excipients.
Obviousness can be established by combining or modifying the teachings of the prior art to
produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the
motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to use a concentration of mannitol in the composition that Ohrem teaches. Xu teaches in Example 3f that PB-111 is dissolved in 1 ml buffer (line 1 in the example), the sample diluted 5-fold (line 1 in the 2nd paragraph) and after loading the column, balanced by 5-fold column volume and column balanced by 2-fold column volume. Considering the experimental steps in Ohrem, mannitol concentration would be a range from 3 mg/ml to 15 mg/ml to 30 mg/ml to 60 mg/ml.
Thus, one would have recognized that applying the teaching of Xu to the
teaching of Ohrem would have yielded predictable results as both references teach mannitol in pharmaceutical compositions and for role of mannitol strong as demonstrating inertness towards both the active pharmaceutical ingredient and the patient’s body (see Abstract). See MPEP
§2143.
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 1-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-6, 8-12, 15 of U.S. Patent No.US8575097B2 in view of H. Leonhard Ohrem et al., hereinafter Ohrem (H. Leonhard Ohrem et al., Why is mannitol becoming more and more popular as a pharmaceutical excipient in solid dosage forms? Pharm Dev Technol, 2014; 19(3): 257–262) further in view of Surinder M. Singh et al., hereinafter Singh (Surinder M. Singh et al., Mechanisms of m-cresol induced protein aggregation studied using a model protein cytochrome c, J Pharm Sci, 2011; 100(5): 1679-1689). Although the claims at issue are not identical, they are not patentably distinct from each other.
Regarding claim 1, reference patent ‘097 teaches the composition comprising polymer conjugated to the cysteine residue of the exendin variant (see claims 1-6, 8, 15). Embodiments of the specification in the reference patent ‘097 disclose ‘composition’ as comprising buffer system with a pH of about 3.0 to about 6.0, or phosphate buffer solution with a pH of about 5.0 to about 9.0 (page 35, Col 19, 4th paragraph).
Regarding claim 2, reference patent ‘097 teaches the composition (see claim 8, 15). Embodiments of the specification in the reference patent ‘097 disclose solvent in the composition (see page 35, Col 19, last paragraph).
Regarding claim 3, reference patent ‘097 teaches the composition (see claim 8, 15). Embodiments of the specification in the reference patent ‘097 disclose ‘composition’ as comprising buffer system, and preferably, the buffer system is acetate buffer solution with a pH of about 3.0 to about 6.0, or phosphate buffer solution with a pH of about 5.0 to about 9.0 (page 35, Col 19, 4th paragraph).
Regarding claim 4, reference patent ‘097 teaches the composition and carrier (see claim 8, 15). Embodiments of the specification in the reference patent ‘097 disclose ‘composition’ as comprising acetate, citrate, borate, phosphate (page 35, Col 19, 4th paragraph).
Regarding claim 5, reference patent ‘097 teaches the composition and carrier (see claim 8, 15). Embodiments of the specification in the reference patent ‘097 disclose ‘carrier’ as all physiologically compatible salts, solvents, dispensing medium, coating, antibacterial agents and antifungal agents, isotonic and absorption delaying agents, etc. In some embodiments, the carrier is suitable for intravenous, intramuscular, subcutaneous, spinal or epidermis dosing (such as by injection or infusion) (page 35, Col 19, 1st paragraph).
Regarding claim 6, reference patent ‘097 teaches the composition and carrier (see claim 8, 15). The composition comprises Exendin variant disclosed in the specification of the reference patent ‘097 to comprise 0.20 mg/ml-5 mg/ml (see page 36, Col 21, 1st paragraph).
Regarding claim 7, reference patent teaches pharmaceutical composition and optionally a pharmaceutical carrier. Embodiments of the specification of the reference patent ‘097 teach isotonic agents -mannitol, sodium chloride, glycerol (see page 36, Col 22, 3rd paragraph, 4th line) in the composition.
Reference patent ‘097 does not teach osmotic pressure regulator is 5-100 mg/ml.
Ohrem teaches that mannitol excels regarding its physicochemical characteristics such as a low hygroscopicity, a strong inertness towards both the active pharmaceutical ingredient and the patient’s body (see Abstract). Ohrem specifically teaches that pharmacopoeias have set limits of 0.2% and 0.3% for sorbitol and mannitol, respectively. This reflects also the regular levels in marketed excipients.
Obviousness can be established by combining or modifying the teachings of the prior art to
produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the
motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to use a concentration of mannitol in the composition that Ohrem teaches. Reference patent ‘097 teaches in Example 3f that PB-111 is dissolved in 1 ml buffer (line 1 in the example), the sample diluted 5-fold (line 1 in the 2nd paragraph) and after loading the column, balanced by 5-fold column volume and column balanced by 2-fold column volume. Considering the experimental steps in Ohrem, mannitol concentration would be a range, ranging from 3 mg/ml to 15 mg/ml to 30 mg/ml to 60 mg/ml.
Thus, one would have recognized that applying the teaching of the reference patent ‘097 to the
teaching of Ohrem would have yielded predictable results as both references teach mannitol in pharmaceutical compositions and for role of mannitol strong as demonstrating inertness towards both the active pharmaceutical ingredient and the patient’s body (see Abstract). See MPEP
§2143.
Regarding claim 8, reference patent ‘097 teaches m-cresol, benzyl alcohol, methyl p-hydroxybenzoateparabens (page 36, Col 22, 2nd paragraph, line 6) (i.e. bacteriostat) in the composition. (see claim 8).
Reference patent ‘097 does not teach 0.1-5 mg/ml.
Singh teaches Protein formulations that contain APs are critical for many therapeutic and vaccine applications. Preservatives are also required for drug delivery systems such as injection pens that are used in multiple doses. Specifically, Singh teaches that m-cresol (CR) is an effective AP and is used at low levels (0.3%) in peptide and protein formulations (i.e. 3 mg/ml) (see Introduction, 2nd paragraph, 1st line).
Obviousness can be established by combining or modifying the teachings of the prior art to
produce the claimed invention where there is some teaching, suggestion, or motivation to do so. In re Kahn, 441 F.3d 977, 986, 78 USPQ2d 1329, 1335 (Fed. Cir. 2006) (discussing rationale underlying the
motivation-suggestion-teaching test as a guard against using hindsight in an obviousness analysis).
Consequently, it would have been prima facie obvious to one of ordinary skill in the art before
the effective filing date of the claimed invention to use the concentration of m-cresol in Singh.
Thus, one would have recognized that applying the teaching of the reference patent ‘097, specifically teaching m-Cresol in the composition, to the teaching of Singh would have yielded predictable results as both references teach m-cresol in pharmaceutical compositions and for the role of m-cresol in reducing protein aggregation (see Abstract). See MPEP §2143.
Regarding claim 9, reference patent ‘097 teaches administration (see claim 9).
Regarding claim 10 reference patent ‘097 teaches administration and treating diabetes (see claim 9, 11).
Regarding claim 11, reference patent ‘097 teaches PEG is 20-29 kDa (see claim 1).
Regarding claim 12, reference patent ‘097 teaches carriers (see claim 8). Embodiments of the specification in the reference patent ‘097 disclose ‘composition’ as comprising acetate, citrate, borate, phosphate (page 35, Col 19, 4th paragraph).
Regarding claim 13, reference patent ‘097 teaches carriers (see claim 8). Embodiments of the specification in the reference patent ‘097 disclose ‘composition’ as comprising acetate, citrate, borate, phosphate (page 35, Col 19, 4th paragraph).
Regarding claim 14, reference patent ‘097 teaches carriers (see claim 8). Embodiments of the specification in the reference patent ‘097 disclose ‘composition’ as comprising acetate, citrate, borate, phosphate (page 35, Col 19, 4th paragraph).
Regarding claim 15, reference patent ‘097 teaches carriers (see claim 8). Embodiments of the specification in the reference patent ‘097 disclose ‘composition’ as comprising lactate (see page 36, Col 22, 3rd paragraph, line 12).
Regarding claim 16, reference patent ‘097 teaches exendin variant conjugate (see claim 8). The composition comprises Exendin variant, disclosed in the specification of the reference patent ‘097 to comprise 0.20 mg/ml-5 mg/ml (see page 36, Col 21, 1st paragraph).
Regarding claim 17, Xu teaches reference patent ‘097 teaches exendin variant conjugate (see claim 8). The composition comprises Exendin variant, disclosed in the specification of the reference patent ‘097 to comprise 0.20 mg/ml-5 mg/ml (see page 36, Col 21, 1st paragraph).
Regarding claim 18, the obviousness rationale has been set forth in the rejection for claim 7.
Regarding claim 19, the obviousness rationale has been set forth above. Reference patent ‘097 teaches m-Cresol in the composition (page 36, Col 22, 2nd paragraph, line 6). See claim 8.
Regarding claim 20, the obviousness rationale has been set forth in the teachings of reference patent ‘097 and Singh. Regarding the limitation 2.0-2.5 mg/ml, generally, differences in concentration or temperature will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration or temperature is critical. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See §2144.05.
Conclusion
No claim is allowed.
Correspondence
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/ARCHANA VARADARAJ/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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