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 is a 371 of PCT/EP2020/082950 (11/20/2020) as reflected in the filing receipt issued on 9/13/2023.
Information Disclosure Statement
The information disclosure statements (IDS) filed on 5/19/2023 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawings
The drawings are objected to for the following reasons:
37 CFR 1.84(u)(1) states “View numbers must be preceded by the abbreviation “FIG.”.
In the current case, the view numbers for Figures 1-3 are preceded by the word “Figure” instead of the abbreviation “FIG.”. View numbers should be updated to recite the abbreviation “FIG.”. Any changes to the drawings should also be reflected in the specification.
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.
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 16-35 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 16 recites “aqueous buffers comprising acetate, phosphate, TRIS base…are used as at least one buffer”. Similarly, claim 27 recites “using aqueous buffers comprising the compounds acetate, phosphate, TRIS base”. The use of the plural “buffers” makes the scope of the claim unclear. Specifically, it is not clear whether this refers to multiple buffers, wherein one buffer is acetate, one is phosphate, and one is TRIS base, or multiple buffers wherein each buffer includes all three of these components.
Claim 16 recites “for each said liquid chromatography”. Claim 27 recites “each said first and second liquid chromatography” There is insufficient antecedent basis for these limitations in the claim. Claims 16 and 27 recite "a first liquid chromatography and a second chromatography". There is no recitation of a second liquid chromatography. Therefore, the limitation “each said liquid chromatography” or “said first and second chromatography” lacks antecedent basis, as there is no prior recitation of a second liquid chromatography.
Claims 17-26 and 28-35 are included in this rejection as they depend on a rejected claim and do not clarify the issue.
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 21 and 30 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 21 recites “the method of claim 16, wherein said aqueous buffers consist of water,
acetate, phosphate, TRIS base, and optionally sodium hydroxide and/or sodium chloride”. Claim 30 recites “the method of claim 27, wherein said aqueous buffers consist of water, acetate, phosphate, TRIS base, and optionally sodium hydroxide and/or sodium chloride”. Claim 16 recites “aqueous buffers comprising acetate, phosphate, TRIS base, and optionally sodium hydroxide and/or sodium chloride are used”. Claim 27 recites “performed using aqueous buffers
comprising the compounds acetate, phosphate, TRIS base, and optionally sodium hydroxide
and/or sodium chloride”. Therefore, dependent claims 21 and 30 do not add any additional limitations that are not already recited in claims 16 and 27.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
Claim Rejections - 35 USC § 102
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.
Claims 16-21, 25-30, and 34-35 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Skudas US 9,149,738 B2, as evidenced by Sigma Aldrich Tris reference.
Regarding claims 16-21, Skudas teaches liquid chromatography techniques, affinity chromatography and ion exchange chromatography, for the purification of biological molecules such as proteins (Skudas col. 1 “Background of the Invention”; col. 9 lines 43-50; col. 10 lines 13-20). Skudas teaches a flow through purification process comprising at least two liquid chromatography steps, including anion or cation exchange, mixed-mode, or hydrophobic interaction chromatography, or combinations thereof (Skudas col. 28 lines 5-19).
Skudas teaches the use of buffers or solvents for loading, washing, eluting, and re-equilibrating the chromatography matrices (Skudas col. 12 lines 44-46). A rinse buffer as set forth in the instant invention is also referred to as a re-equilibration buffer (see instant specification pg. 6 lines 25-29). Buffers taught by Skudas are MES, MOPS, MOPSO, Tris, HEPES, phosphate, acetate, citrate, succinate, and ammonium buffers, as well as combinations of these (Skudas col. 12 lines 40-44). TRIS base, as defined in the instant specification, refers to the compound 2-Amino-2-(hydroxymethyl)-1,3-propanediol, corresponding to CAS number 77-86-1, which is also commonly known as Tris (specification pg. 8 lines 10-11; see Sigma Aldrich Tris reference). Thus, a skilled artisan could immediately envisage utilizing buffers comprising acetate, Tris (TRIS Base), and phosphate, or combinations of these, as Skudas teaches that all three of these, as well as combinations thereof, are suitable buffers.
Skudas teaches that the wash buffer and loading buffer are typically the same, and that the loading buffer is used for re-equilibrating (Skudas col. 12 lines 64-67; col. 13 lines 7-10). Therefore, a buffer as taught by Skudas, which includes buffers comprising acetate, Tris, and phosphate and combinations thereof, can be used as a wash, loading, and re-equilibrating (rinse) buffer; i.e. at least one (claims 16, 21), two (claims 17-18) or three (claims 19-20) buffers selected from an equilibration buffer, a loading adjustment buffer, a wash buffer, an elution buffer, a regeneration buffer and a rinse buffer in the first and/or second liquid chromatography.
Regarding claims 27, 29, and 30, Skudas teaches a method for purifying a protein using at least a first and second liquid chromatography step, as set forth above. This process involves re-equilibrating (rinsing) the chromatography matrix with a buffer prior to loading a target molecule, and washing the chromatography matrix with a buffer (Skudas col. 12 lines 64-67; col. 13 lines 1-6). As discussed above, Skudas teaches aqueous buffers for these purposes comprising acetate, phosphate, and Tris. The chromatography matrix refers to a solid phase chromatography material such as an ion exchange matrix (Skudas col. 10 lines 12-20, 40-46). Therefore, Skudas teaches at least one step selected from the group consisting of equilibrating a solid stationary phase, washing a solid stationary phase, eluting the protein of interest, and regenerating a solid stationary phase, performed using aqueous buffers comprising the compounds acetate, phosphate, TRIS base (claims 27, 30). Skudas teaches that at least two of these steps (re-equilibrating, washing) are performed using the aqueous buffers (claim 29).
Regarding claim 28, Skudas teaches (a) purifying a protein using a first liquid chromatography step with a solid stationary phase to obtain a protein of interest eluent, i.e. a flow through anion exchange step wherein the target molecule flows through (Skudas col. 28 lines 19-24). Skudas further teaches (b) further purifying the protein of interest eluted from the first chromatography step with a second liquid chromatography step comprising a solid stationary phase, i.e. an additional flow through step comprising cation exchange chromatography (Skudas col. 28 lines 60-65). The buffers used for the equilibrating, washing, eluting, and regenerating steps are taught by Skudas as set forth above.
Regarding claims 25 and 34, Skudas teaches that the protein of interest for purification is an antibody (Skudas col. 7 lines 4-12).
Regarding claims 26 and 35, the “wherein” clause is directed to a characteristic of the protein being purified by the claimed method, the isoelectric point. The isoelectric point of the protein does not result in a manipulative difference in the claimed method, which is directed to purification of any protein of interest by liquid chromatography. Therefore, the method of Skudas, directed to purification of a protein using a first and second liquid chromatography and using the buffers as instantly claimed, anticipates the method of claims 26 and 35.
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.
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 22-24 and 31-33 are rejected under 35 U.S.C. 103 as being unpatentable over Skudas et al. as applied to claims 16-21, 25-30, and 34-35 above.
Regarding claims 22-24 and 31-33, Skudas teaches the method of claims 16 and 27 as set forth above. Skudas does not teach the specific molar ratios of acetate, phosphate, and Tris base as claimed. However, the concentrations of buffer used would have been routinely optimized by a skilled artisan based on the other assay conditions. Skudas clearly teaches that the buffers are provided in a concentration effective to achieve the result of protein/antibody purification. That means the conditions necessary to achieve the protein purification were result-effective variables. Result-effective variables would be optimized through routine experimentation by one having ordinary skill in the art. Furthermore, differences in concentration will not support the patentability of subject matter encompassed by the prior art unless there is evidence indicating such concentration is critical. See MPEP 2144.05(II)(A). Therefore, the claimed molar ratios of acetate, phosphate, and Tris base used in the liquid chromatography buffers are obvious in view of Skudas.
Claims 26 and 35 are rejected under 35 U.S.C. 103 as being unpatentable over Skudas et al. as applied to claims 16-21, 25-30, and 34-35 above, and further in view of Bian et al., WO 2013/028330 A2.
Skudas teaches the method of claims 16 and 27 as set forth above. Skudas does not teach that the protein of interest has an isoelectric point between 6.5 and 9.5 as recited in claims 26 and 35.
Regarding claims 26 and 35, the “wherein” clause is directed to a characteristic of the protein being purified by the claimed method, the isoelectric point. The isoelectric point of the protein does not result in a manipulative difference in the claimed method, which is directed to purification of a protein of interest, as discussed above. However, Bian teaches protein purification methods involving multiple liquid chromatography steps, used for the purification of antibodies (Bian pg. 1 para. 2, pg. 3 para. 11, pg. 23 para. 96). Bian teaches that antibodies are known to have isoelectric points that are usually above 7 (Bian pg. 35 para. 139).
It would have been obvious to a skilled artisan, given the teachings of Bian that antibodies typically have isoelectric points above 7, to use a protein (antibody) having an isoelectric point in the range of 6.5 to 9.5 in the method of Skudas, which is similarly directed to antibody purification.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to EMILY F EIX whose telephone number is (571)270-0808. The examiner can normally be reached M-F 8am-5pm ET.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Sharmila Landau can be reached at (571)272-0614. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/EMILY F EIX/Examiner, Art Unit 1653
/JENNIFER M.H. TICHY/Primary Examiner, Art Unit 1653