DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. The Preliminary Amendment filed on August 2, 2024, has been received and entered.
Claim Disposition
3. Claims 1-14 are pending and are under examination.
Abstract
4. The abstract is objected to for the following informalities:
“The present invention relates to…….reducing impurities, for example, Host Cell Proteins (HCP) [[such as]] from …..”.
Appropriate correction required.
Information Disclosure Statement
5. The Information Disclosure Statement filed on August 2, 2024, has been received and entered. The references cited on the PTO-1449 Form have been considered by the examiner and a copy is attached to the instant Office action.
Drawings
6. The drawings filed on December 11, 2023 are accepted by the examiner.
Specification Objection
7. The specification is objected to for the following informalities:
The specification is objected to because the sequence notation is improper, see “SEQ ID No.:31” (see page 12), which should be ‘SEQ ID NO: 31’.
Appropriate correction is required.
Claim objection
8. Claims 1-14 are objected to for the following informalities:
For clarity and precision of claim language it is suggested that claim 1 is amended to delete the “optionally” language.
For clarity it is suggested that claim 1 is amended to read, “A method for reducing impurities in an eluate with [[comprising a product]] Fc-containing monoclonal antibody, [[the method]] comprising:
providing a load fluid comprising [[a product]] the Fc-containing monoclonal antibody and one or more impurities [[,wherein the product is an Fc-containing monoclonal antibody]],……”.
For clarity it is suggested that claim 1 is amended to read, “…..with [[another]] a second wash solution….”.
For clarity and precision of claim language it is suggested that claim 1 is amended to read, “….arginine salt or [[other]] arginine derivative……”. The dependent claims hereto are also included.
For clarity it is suggested that claim 10 is amended to read, “…..host cell protein or variant thereof, a nucleic acid or variant thereof, [[a product variant]] and/or an endotoxin”.
For clarity it is suggested that claims 5-7 are amended to spell out the acronyms.
For clarity it is suggested that claim 11 is amended to delete “optionally”.
For clarity and precision of claim language it is suggested that claim 12 is amended to recite either between or about but not both together (i.e., pH of about 2 to about 5).
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.
9. Claims 1-14 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.
Claims 1-14 are indefinite for the recitation of "such as” pertaining to the number of wash solutions in claim 1 and the specific antibody in claims 5-7, because the phrase ‘such as’ introduces ambiguity thus indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention, the phrase suggest an open-ended list without clear limits.. See MPEP 2173.05(d)
Claim 1 is indefinite for the recitation of “about 500mM because there is no upper limit with “about” thus no clear amount for the concentration, is it 501, 550, 600, 700 etc? See for example, claims 8-9 with similar language. The dependent claims hereto are also included.
Claim 3 lacks clear antecedent basis for the recitation of “about” in the ranges recited for pH because the ‘about’ language puts the values at +5, +10, or +15 which means that the value would be lower than 8 and the independent claim recites ‘greater than 8.0’ for the pH.
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.
10. 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.
11. Claim(s) 1-14 is/are rejected under 35 U.S.C. 103 as being unpatentable over US Patent No. 9,663,552 (May 30, 2017) in view of Vanderlaan (April 25, 2018, Wiley online library) and Kawooya (US Patent No. 11,312,745, July 22, 2016).
The primary reference teaches a washing and method for affinity chromatography (a type of Protein A chromatography) in which a wash solution comprising arginine or an arginine derivative, at pH greater than 8 is effective in removing impurities without the presence of a non-buffering salt while simultaneously increasing product concentration in the eluate and maintaining a high percent yield of recovered product (see abstract and paragraphs 11-14). The impurities removed buyer chromatography column includes host cell proteins (HCP), among others (see column 1). The reference teaches that the product is an antibody. In addition the reference teaches that arginine has been used to elute proteins from affinity chromatography columns and other types of purification columns for example eluting antibodies from a protein a column (see column 1). The reference also teaches that suitable antibody or antibody fragment can be an Fc region or an Fc fusion protein (using a protein a column and loading a mixture comprising a anybody or anybody fragment, wash and the protein a column with a wash solution comprising arginine or an arginine derivative at a pH greater than eight or about 8.5 (with a concentration that is equivalent to the language of about 500mM (see paragraph 14).
The reference also teaches that the arginine salt/derivative can be acetyl arginine, agmatine to name a few (see paragraphs 13-14). The reference does not teach the specific monoclonal antibodies (mAb), however, the reference makes it clear that arginine has key benefits in mAb purification such as reducing impurities like endotoxins and host cell proteins. CGRP, PACAP and ACTH-1 are specific mAb not taught by the reference but as established in the art as important and needing the purification provided herein, thus would be obvious for one of ordinary skill in the art to swap out the generic Fc-containing mAb for one of those specific ones (see Vanderlaan et al. with some additional mAb, in the abstract). Specifically, the art discloses Antibodies and Fc fusion proteins that may be purified using the methods described herein may bind to one or more proteins including, but not limited to, CD2, CD3, CD4, CD8, CD11a, CD14, CD18, CD19, CD20, CD22, CD23, CD28, CD25, CD33, CD40, CD44, CD52, CD80 (B7.1), CD86 (B7.2), CD147, IL-1α, IL-1β, IL-4, IL-5, IL-8, IL-10, IL-13, IL-2 receptor, IL-4 receptor, IL-6 receptor, IL-13 receptor, IL-I8 receptor subunits, angiopoietin (e.g. angiopoietin-1, angiopoietin-2, or angiopoietin-4), PDGF-β, VEGF, TGF, TGF-β2, TGF-β1, EGF receptor, VEGF receptor, FGF receptor, C5 complement, Beta-klotho, calcitonin gene-related peptide (CGRP), CGRP receptor, pituitary adenylate cyclase activating polypeptide (PACAP), pituitary adenylate cyclase activating polypeptide type 1 receptor (PAC1 receptor), IgE, tumor antigens, e.g., tumor antigen CA125, tumor antigen MUC1, PEM antigen, PD-1, LCG (which is a gene product that is expressed in association with lung cancer), HER-2, a tumor-associated glycoprotein TAG-72, the SK-1 antigen, integrin alpha 4 beta 7…….(see paragraph 40 of Kawooya).
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed invention as a whole because the combined teaching of the references render the claimed invention as obvious. One of ordinary skill in the art would be motivated to combine the references because they are analogous art. Moreover, the Supreme Court pointed out in KSR, “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR, 127 S. Ct. at 1741. The Court thus reasoned that the analysis under 35 U.S.C. 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the “inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 1741. The Court further advised that “[a] person of ordinary skill is…a person of ordinary creativity, not an automation.” Id. at 1742. Therefore, the claimed invention was obvious to make and use at the time the invention was made and was prima facie obvious.
Conclusion
12. No claims are presently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOPE A ROBINSON whose telephone number is (571) 272-0957. The examiner can normally be reached 9-5pm on Monday to Friday.
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/HOPE A ROBINSON/Primary Examiner, Art Unit 1652
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