equivalently) is detrimental to asparaginyl stability is a very important discovery in this work, and is shown dramatically in Example 1 below. 

"Pharmaceutically-acceptable": In the context of this invention, "pharmaceutically-acceptable" designates com› pounds or compositions in which each excipient is approved by the Food and Drug Administration, or a similar body in another country, for use in a pharmaceutical or vaccine for› mulation, or belongs to a succinct class of compounds for which a Drug Master File is on file with a govermnent regu› latory agency, usually the FDA, or, less preferably, is known from extensive toxicity studies to be safe for the intended route of administration (which in the context of this invention is typically, though not always, parenteral). This also includes compounds that are major components of approved excipi› ents, which are known to be oflow toxicity taken internally. A listing of approved excipients, each with the various routes of administration for which they are approved, was published by the Division of Drug Information Resources of the FDA in January, 1996 and entitled "Inactive Ingredient Guide". The existence of a Drug Master File at the FDA is additional evidence that a given excipient is acceptable for pharmaceu› tical use, at least for certain routes of administration. For injectable products, a listing of approved excipients was pub› lished in 1997. See Nema, Washkuhn and Brendel (1997) PDA J. of Pharm. Sci. & Technol. 51(4):166. It should be added that there are certain compounds, such as vitamins and amino acids, which are in injectable products (typically for parenteral nutrition) as "actives", and are thus known to be safe upon injection, and such compounds are considered herein as pharmaceutically-acceptable as excipients as well, for injection. All of the embodiments of this invention are understood to be pharmaceutically-acceptable for at least some route of administration in humans, meaning that every excipient in each embodiment is approved for use in humans, in at least one route of administration. This is crucial not only for product safety but also for utility of the invention, as a key feature of the invention is that it uses, preferentially, only FDA-approved excipients, most of which are in fact approved for injection. Examples of compounds that are not pharma› ceutically-acceptable are taurocholic acid and its salts (not acceptable for any route of administration), dichloroacetic acid, sodium p-chlorobenzenesulfonate, and other N-acety› lated amino acids besides N-acety ltryptophan. The surprising recognition that deamidation-stabilizing formulations can be found and produced within the narrow range of pharmaceu› tically-acceptable formulations is a key aspect of this inven› tion, particularly as it recognizes the destructive effects of anions that do not fit the preferred range of pKa as described herein. 

"Saccharin": To avoid any confusion, it is pointed out that in spite of the name-saccharin, which sounds like it should be related to saccharides-and the sweet taste, saccharin is not a pol yo 1, nor any kind of sugar. The name reflects only the sweetness, not the chemical structure. The chemical structure 55 is in fact 2,3-dihydro-3-oxobenzisosulfonazole (C$_{7}$H$_{5}$NO$_{3}$S). 

Description 

Surprisingly, in the course of experimental work by the inventor supported by theoretical considerations, and exem- plified by the Examples below, it was found that asparaginyl stability of peptide ( or protein) solutions containing organic anions drops off sharply above an anion pKa of about 3.5, and that for pKa values equal to or greater than about 3.5 the organic anion can actually destabilize the drug. A dramatic cutoff between stabilization and destabilization at the pKa value of3.5 was reported by the inventor in connection with 

a small-molecule de-esterification hydrolysis reaction, in U.S. patent application Ser. No. 11/404,109. Since at the solution pH value of preferred embodiments of the invention, at least 90% of the organic anion is deprotonated, and since the amount protonated (i.e., in acid form) decreases in the more effective (lower pKa) cases, this trend is almost cer› tainly not strongly dependent on the pH of the solution (pro› vided it is not too strongly acidic), but rather, is largely inde› pendent of pH and thus "universal" in some sense. Hence, quite broadly, a pKa equal to or less than about 3.5 is strongly preferred in the practice of this invention. A less dramatic, though significant, drop-off in stabilizer effectiveness is also observed as the pKa drops down to negative values. Thus, saccharin, benzenesulfonic acid, N-acetyltryptophan and gentisic acid are strongly preferred in this invention, and much preferred over compounds above pKa 3.5 such as or acetic or citric acid, which are actually destabilizing. The destabilizing effect of acetate ion, for example, with its pKa of 4.5, is demonstrated in Example 1 below. Without wishing to be bound by theory, when a destabilizing anion (with pKa greater than 3.5) is present in molar concentrations about equal to or greater than that of the preferred anion (with pKa less than or equal to 3.5), it may compete with the preferred anion for binding to the labile group (viz., at the carbonyl carbon of the labile group), and effectively displace it because it is a poorer leaving group, thereby rendering the preferred anion far less effective, if not substantially ineffective. 

Organic anions that have two acidic/anionic groups may need to be treated in the same way as mixtures of anions. In particular, one destabilizing acidic group, with a pKa greater than about 3.5, might nullify the stabilizing effect of an acidic group on the same molecule with a pKa less than or equal to 3.5. Thus, for example, tartaric acid, with a pKa$_{1 }$ of2.93 and a pKa$_{2 }$ of 4.23, will not afford effective stabilization in the context of this invention. This is apparently related to the fact that the weaker acidic group (higher pKa) forms a stronger conjugate base than does the stronger acidic group. For a similar reason, phosphoric acid is a destabilizing anion in the context of this invention. In this evaluation of organic anions, any titratable acidic group with a pKa that is too high to be relevant should be removed from consideration, in particular if the pKa is more than about 1 pH point above the pH of the formulation. 

Organic zwitterions behave, not surprisingly, very differ› ently from the organic anions within the context of the current invention, and the effect of an acidic group with a pKa within the preferred ranges of the invention is largely nullified by the cationic moiety in the zwitterion. Thus, while the acidic group on a typical amino acid, for example, is between 2.0 and 2.5, and so well within the preferred range, the zwitterionic amino acids are not effective as stabilizers and are not to be deemed as organic anions of the invention; this is not necessarily true for acidic amino acids such as aspartic acid and glutamic acid. 

Without wishing to be bound by theory, one explanation for stabilizer effectiveness when the pKa of the stabilizer is in the preferred range of 0.5-3.5, and particularly in the most pre› ferred range between 1.5 and 3.5, is that the conjugate base may form a temporary covalent bond, or other type of com› plex, with the carbonyl carbon of the labile group on the peptide or protein, at least a fraction of the time, limiting access of the carbonyl to other nucleophilic attack. This is driven by the susceptibility of the carbon atom on the carbo› nyl group to nucleophilic attack, and in nucleophilic attack on carbonyl groups generally, reactivity correlates fairly strongly with basicity. If the pKa of the acid is too low, then the conjugate base is extremely weak, and will less frequently attack the carbonyl group. Thus, a stabilizer such as saccharin 

