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 .
Claim Status
Claims 1-14 are currently pending.
Information Disclosure Statement
The listing of references in the specification is not a proper information disclosure statement. 37 CFR 1.98(b) requires a list of all patents, publications, or other information submitted for consideration by the Office, and MPEP § 609.04(a) states, "the list may not be incorporated into the specification but must be submitted in a separate paper." Therefore, unless the references have been cited by the examiner on form PTO-892, they have not been considered.
The information disclosure statement (IDS) submitted on 30 August 2024 has been considered by the examiner.
Specification
The disclosure is objected to because of the following informalities: paragraph [0010] recites “∆%HMW” and this notation is also found in Figure 2. The meaning of this recitation is not readily clear from either paragraph [0010] or the Figure and therefore, the meaning of at least “HMW” is necessary to understand the disclosed information.
The specification at paragraph [0044] recites “Convention lyophilization was used as a control”. The term “convention lyophilization” is not known to be a term of the art and it would seem that the term “conventional” should replace “convention”.
Appropriate correction is required.
Claim Objections
Claims 3-14 are objected to under 37 CFR 1.75(c) as being in improper form because a multiple dependent claim should refer to other claims in the alternative only (see claim 3) and cannot depend from any other multiple dependent claim (see claims 4-14). See MPEP § 608.01(n). Accordingly, the claims have not been further treated on the merits.
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 1-3 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.
The term “high” in claim 1 is a relative term which renders the claim indefinite. The term “high” is not defined by the claim, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. Because the term “high” cannot be determined, the metes and bounds of what types of protein formulations are intended by the instant claims.
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.
Claim(s) 1-2 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by US PatPub. 2018/0099049 A1 (Tang et al.).
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.
Claim(s) 1-2 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bhambhani et al. (J Pharm Sci 101: 1120-1135, 2012) in view of WO2021/158759 A2 (Tang et al.).
Bhambhani et al. teach a method for selecting excipients for inclusion in a high concentration Fc-containing protein formulation (see abstract and title). Bhambhani et al. screened an excipient library using an aggregation assay at low mAb concentrations (4 mg/mL) and potential stabilizers were identified. The ability of these excipients to prevent conformational alterations in high concentration mAb solutions (100 mg/mL) was determined by monitoring tertiary structure changes using an intrinsic fluorescence method, wherein the method comprises the steps of: (a) combining at least one excipient with a preparation comprising an Fc containing protein (see Figure 8). The ability of excipients to prevent conformational alterations in high concentration mAb solutions (100 mg/mL) was determined by monitoring tertiary structure changes using an intrinsic fluorescence method. Bhambhani et al. teach that these studies resulted in identification of various stabilizers that both inhibited aggregation and increased the fluorescence transition onset temperature. Bhambhani et al. fails to teach (b) conducting a controlled nucleating cycle on the preparation from step (a); (c) drying the preparation from step (b) under a vacuum; and (d) stoppering with and/or without a vacuum.
Tang et al. teaches a method of making lyophilized compositions of proteins, including antibodies, by conducting a controlled nucleating cycle on the preparation (see [0060]; 'A controlled nucleation step was used during the freezing stage of the lyophilization process, since how a product freezes can impact its subsequent drying behavior and the final product quality attributes. Controlled nucleation can promote rapid rate of crystallization, such as formation of larger ice crystal.'); and (c) drying the preparation from step (b) under a vacuum (see [0061] – ‘The secondary drying was conducted at same shelf temperature of the primary drying by extending the primary drying.'; see [0006] - 'and conducting secondary drying on the formulation to remove the desorbed solvent molecules to obtain a target weight percentage of the solvent molecule in the lyophilized cake, wherein the secondary drying is conducted at a relatively high shelf temperature at or above 25 °C under high vacuum, such as below 200-millitorr of chamber pressure.').
Tang et al. also teaches methods of developing an antibody formulation containing excipients (para [0060] - 'Protein formulations containing MABB (a monoclonal antibody) were used for the lyophilization, such as a formulated drug substance comprising 50 mg/mL MABB, 10 mM acetate, 25 mM arginine hydrochloride, 0.2% polysorbate 80 and 5% sucrose at pH 5.3. The ratio of sucrose to protein was 1:1.'; see [0033] - Excipients can help to stabilize the drug substance and/or add bulk to the formulation. The term ingredient can be used interchangeably with excipients. Excipients include various substances for various purposes like buffering, bulking, solubilizing, stabilizing, plasticizing, and protecting the drug substance. Protectants can protect against thermal stress and/or physical stress like agitation. Cryoprotectants can protect protein from freezing stresses such as ice interface stress and freezing concentration stress. Lyoprotectants can protect protein from freezing and dehydration stresses. Excipients may include stabilizers. A stabilizer can be added to the pre-lyophilized solution to stabilize the protein against aggregation or other degradation.'; see [0034] ‘The needs of generating biopharmaceutical formulations which have stabilities for long-term storage at room temperature have led to an increasing demand for developing lyophilization processes. This disclosure provides methods to satisfy the aforementioned demands by providing methods for lyophilization of biopharmaceutical formulations to generate lyophilized products which have desirable characteristics and residual moisture contents').
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the method of Bhambhani et al. by including the steps from the method of Tang et al., and additionally (d) stoppering the formulation with and/or without a vacuum, to provide an improved screening process for excipients in a lyophilized composition and obtain a Fc-containing protein formulation with increased stability according to Tang et al. (see Abstract - Lyophilization methods for preparing protein formulations for long-term storage at room temperature or improved stability at refrigeration storage are provided.'). Regarding claim 2, Bhambhani et al. in view of Tang et al. makes obvious the method according to claim 1, wherein Tang et al. further teaches secondary drying is not employed (Abstract - 'Alternatively, the lyophilization can be conducted without a distinguished secondary drying step.').
While neither Bhambhani et al. nor Tang et al. explicitly state that the lyophilized preparation be stoppered after drying (with or without a vacuum), it would have been routine and obvious to one of ordinary skill in the art to stopper the dried preparation because the method prepares a dried preparation and the goal of the method is to remove moisture and stoppering the preparation would prevent moisture from reaching the preparation. Therefore, the invention as a whole would have been prima facie obvious over the prior art of record.
Claim(s) 1 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bhambhani et al. (J Pharm Sci 101: 1120-1135, 2012) and WO2021/158759 A2 (Tang et al.) in view of Tang et al. (US PGPub 2018/0099049).
The disclosure of Bhambhani et al. and WO2021/158759 A2 are provided above. Neither Bhambhani et al. nor Tang et al. (‘759) explicitly state that the lyophilized preparation be stoppered after drying (with or without a vacuum).
Tang et al. (‘049) teaches methods of preparing lyophilized compositions. Tang et al. teach that after drying the preparation, the vial is stoppered (see [0026] and [0033]).
It would have been obvious to one of ordinary skill in the art before the filing date of the claimed invention to practice the method of Bhambhani et al. and Tang et al. (‘759) and to additionally stopper the preparation after drying as taught by Tang et al. (‘049) for the obvious benefit of preventing moisture from reaching the dried preparation.
Citation of Relevant Art
The art made of record and not relied upon is considered pertinent to applicant's disclosure.
Awotwe-Otoo et al. Impact of controlled ice nucleation on process performance and quality attributes of a lyophilized monoclonal antibody. Int. J. Pharma. 450: 70-78, 2013.
Luo et al. Impact of controlled ice nucleation and lyoprotectants on nanoparticle stability during Freeze-drying and upon storage. Int. J. Pharma. 641 (2023) 123084 (14 pages).
.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Christine J Saoud whose telephone number is (571)272-0891. The examiner can normally be reached M-F, 8am-4pm.
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/Christine J Saoud/Primary Examiner, Art Unit 1645
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