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 .
This is the First Office Action on the Merits of US18/682,254 filed on 02/08/2024 which is a 371 of PCT/IB2022/057409 08/09/2022 which claims foreign priority to INDIA 202141036153 08/10/2021. The Filing Receipt filed on 07/03/2024 is controlling.
Claims 1-7 are pending and under examination.
Information Disclosure Statement
The IDS statements filed on May 13, 2024 have been considered by the examiner. Note that CN105153311 and CN110526982 have been only considered to their English language translations provided with the IDS.
Drawings
The drawings are objected to because the text in FIG 1 & 7 is not legible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
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 - This application fails to comply with the requirements of 37 CFR 1.821 - 1.825 because it does not contain a "Sequence Listing" as a separate part of the disclosure or a CRF of the “Sequence Listing.”. Note that page 1 of the Specification contains an amino acid sequence.
Required response - Applicant must provide:
A "Sequence Listing" part of the disclosure; together with
An amendment specifically directing its entry into the application in accordance with 37 CFR 1.825(a)(2);
A statement that the "Sequence Listing" includes no new matter as required by 37 CFR 1.821(a)(4); and
A statement that indicates support for the amendment in the application, as filed, as required by 37 CFR 1.825(a)(3).
If the "Sequence Listing" part of the disclosure is submitted according to item 1) a) or b) above, Applicant must also 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.
If the "Sequence Listing" part of the disclosure is submitted according to item 1) c) or d) above, applicant must also provide:
A CRF in accordance with 37 CFR 1.821(e)(1) or 1.821(e)(2) as required by 1.825(a)(5); and
A statement according to item 2) a) or b) above.
Claim Objections
Claims 1, 4, and 7 are objected to because of the following informalities:
In claims 1 & 7, (part g), the term Isolating should not be capitalized.
In claims 4 & 7, the term Urea should not be capitalized.
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 1-7 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.
Independent claims 1 and 7, in part (a), each recite the limitation "the fermentation broth". There is insufficient antecedent basis for this limitation in the claims because there is no prior reference in the claim to fermentation or a broth.
Also, claims 1, and 7, in part (e), each recite the limitation "the filtered supernatant from step d)". There is insufficient antecedent basis for this limitation in the claims because there is no prior reference in the part (d) or anywhere in the claims to a filtered supernatant.
Claims 2-6 are indefinite as they depend from claim 1 and are not remedial.
Also, claim 5 and base claim 7, each recites the limitation "…wherein mobile phase gradient is a buffer…” There is insufficient antecedent basis for this limitation in the claims because there is no prior reference in the claims to a mobile phase gradient.
Claim 6 is indefinite as it depends from claim 5 and is not remedial.
Also, claim 6 is indefinite because it recites an open-ended list but lacks the term “or” before the last element of the list. Alternatively, the claim could be written as a closed list with the term “and” before the last element of the list. (A closed list may use claim language such as: selected from the group consisting of.)
Also, claim 7 is indefinite because it is written as two separate sentences. The scope is unclear as to whether only the first sentence is required of the claim.
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.
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.
Claims 1-7 are rejected under 35 U.S.C. 103 as being unpatentable over Cheng et al in “A novel strategy to prepare the precursor peptide of liraglutide” (Process Biochemistry, 2017 Vol 62, pages 10-15; available online July 15, 2017), in view of Raghuwanshi et al (WO2016-009451 published 01/21/2016).
Regarding base claims 1 and 7, Cheng et al discloses a method for purifying crude recombinant liraglutide precursor, the method comprising: expressing the precursor peptide of liraglutide using an E.coli protein expression system. (See entire article.) Cheng et al disclose:
a. subjecting a fermentation broth to purification steps including solubilization, and centrifugation, cation exchange, and RP-HPLC (see Section 2.2-2.4 “Protein expression in fermenter” para bridging pages 13-14; Section 3.2)
c. solubilizing the product of step b using urea, followed by centrifugation (see Section 2.3, 2.5; FIG 4 & 6 legends);
e. the filtered supernatant from step d) is subjected to cation exchange chromatography purification step (see Section 2.8);
f. subjecting the product of step e) to a reversed phase high pressure liquid chromatography (RP-HPLC) (see Section 2.9; FIG 4); and
g. isolating the purified liraglutide precursor (see Section 3.3).
However, Cheng et al differs from the presently claimed invention in that they do not explicitly recite the following limitations: that microfiltration is performed at pH 3.0 to 6.0; that diafiltration is performed at pH 3.0 to 6.0; solubilizing is by using urea; and using depth filtration. Also, Cheng et al does not explicitly disclose a mobile phase gradient is a buffer with a pH range of 3.0 to 5.0, or that such buffer is selected from Glycine-HCL buffer, citrate buffer, acetate buffer, citrate-phosphate buffer, succinate buffer, maleate buffer.
Raghuwanshi et al disclose a scalable and industrially viable downstream process for purification of recombinant human G-CSF. Raghuwanshi et al discloses high cell density fermentation producing the recombinant protein in fermentation growth media/broth. (See Abstract, entire reference; page 6, para 2; page 19, Example 1).
Raghuwanshi et al discloses microfiltration is performed at pH 4.0 which meets the limitation of pH 3.0 to 6.0. (See page 21, Step 6.)
Raghuwanshi et al discloses the purification/clarification steps of centrifugation, solubilization, diafiltration, microfiltration, depth filtration (see page 9, para 1-2; Example 1, page 21, para 1).
Raghuwanshi et al discloses the use of urea for solubilizing the purification mixture. (See page 7, para 1; page 20, Step 3).
Raghuwanshi et al discloses ultrafiltration/diafiltration step prior to ion exchange chromatograpy. (See page 7, last para.)
Raghuwanshi et al disclose cation exchange chromatography which comprises a stationary phase and a mobile phase. (See page 10, lines 11-16.) The mobile phase comprises sodium acetate and acetic acid and NaCl at a pH range of 4.0 – 6.0. (See page 11, lines 20-33; page 11, para 1.)
Raghuwanshi et al disclose RP-HPLC. (See page 16, Table 1; page 20, Step 4b; page 22.)
Regarding claim 2, Raghuwanshi et al discloses microfiltration is performed at pH 4.0 which meets the limitation of pH 3.0 to 6.0. (See page 21, Step 6.)
Regarding claim 3, Raghuwanshi et al discloses that ultrafiltration/diafiltration is performed at pH 3.0 to 6.0. (See page 21-22, Step 6.-7)
Regarding claim 4, Raghuwanshi et al discloses that solubilizing is performed by addition of Urea. (See page 7, para 1; page 20, Step 3).
Regarding claim 5, Raghuwanshi et al discloses that mobile phase gradient is a buffer with a pH range of 3.0 to 5.0. Raghuwanshi et al disclose cation exchange chromatography which comprises a stationary phase and a mobile phase. (See page 10, lines 11-16.) The mobile phase comprises sodium acetate and acetic acid and NaCl at a pH range of 4.0 – 6.0. (See page 11, lines 20-33; page 11, para 1.)
Regarding claim 6, Raghuwanshi et al discloses that the buffer is acetate buffer, citrate-phosphate buffer, succinate buffer, or maleate buffer. Raghuwanshi et al discloses that the mobile phase comprises sodium acetate and acetic acid and NaCl at a pH range of 4.0 – 6.0. (See page 11, lines 20-33; page 11, para 1.)
The level of skill in the art was high before the effective filing date of the presently claimed invention.
One of ordinary skill in the art would have been motivated to include the purification steps suggested by Raghuwanshi et al in the purification methods of Cheng et al for the rationale of Raghuwanshi et al of providing optimum yield and purification quality when producing recombinant proteins in the E.coli expression system.
It would have been obvious to incorporate the methods of Raghuwanshi et al because both references are in the field of improving purification of a recombinant protein using an E.coli fermentation process. Further, the elements suggested in Raghuwanshi et al are noted as preferred embodiments for recombinant protein purification by Raghuwanshi et al.
In view of the high skill level in the art it is considered that one of ordinary skill in the art having the cited references before the effective filing date of the presently claimed invention would have had a reasonable expectation of success to combine the purification elements of Raghuwanshi et al with the method of Cheng et al to arrive at the presently claimed invention.
Thus, the claims as a whole are rendered obvious over the cited references.
Conclusion
No claim is allowed.
Prior art which may be applied in a future office action if appropriate:
Jungbauer et al (WO 2021028590 A1 published 02/18/2021). Jungbauer et al discloses purification of recombinant protein produced in a fermentation culture. The procedure discloses purification steps of the presently claimed invention as follows:
According to a specific example, but not limited thereto, wild-type or variant caspase-2 or cp caspase-2 or a fusion protein as described herein is produced in a fermentation process.. The produced caspase or fusion protein can be isolated by cell disintegration e.g. by high pressure homogenization, centrifugation of the cell debris, concentration of the supernatant by tangential flow micro-filtration or the like. Further purification can be done by chromatography, such as ion exchange chromatography, hydrophobic interaction chromatography, size exclusion chromatography, isoelectric focusing, mixed mode chromatography reversed phase high performance chromatography, tangential flow microfiltration, depth filtration, ammonium sulphate, -chloride, - citrate precipitation heat precipitation, solubilization, crystallization, centrifugation or the like.
Prakash et al (CA 2913252 C, published 10/13/2020). Prakash et al discloses methods of purification of recombinant proteins by growth in fermentation culture/broth and, HPLC assay, a mobile phase gradient program procedure (See Example 20).
Any inquiry concerning this communication or earlier communications from the examiner should be directed to CATHERINE S HIBBERT whose telephone number is (571)270-3053. The examiner can normally be reached M-F 8:00-5:00.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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CATHERINE S. HIBBERT
Primary Examiner
Art Unit 1658
/CATHERINE S HIBBERT/Primary Examiner, Art Unit 1658
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