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 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.
Claim(s) 1-19 is/are rejected under 35 U.S.C. 103 as being unpatentable over Bay (US 7,544,833, hereinafter “US’833”) in view of Leone-Bay (US 6,346,242, hereinafter “US’242”) and further in view of Leone-Bay (US 5,650,386, hereinafter “US’386”), as set forth below.
US’833 is directed to methods for preparing N-(8-[2-hydroxybenzoyl]amino)caprylic acid (NAC) and its alkali metal salts, including sodium salts (SNAC). US’833 teaches:
Reacting a salicylic-acid-derived benzoyl moiety with an ω-amino fatty acid to form N-acylated salicylate amides corresponding to NAC (see US’833, col. 3, ll. 15–45; col. 4, ll. 1–35; claims 1–4).
Use of salicylic acid derivatives and activated forms in amide-forming reactions with amino-fatty acids (see col. 5, ll. 10–40).
Conversion of the resulting carboxylic acid to alkali metal salts, including sodium salts, by neutralization with base (see col. 6, ll. 5–25; Example 3).
Isolation of SNAC as a solid product (see Example 4).
Accordingly, US’833 teaches a method corresponding to claim 1, including reacting a salicylate-derived compound with an amino-fatty acid to obtain a compound of formula (I) and forming alkali metal salts thereof.
US’242 discloses alternative and conventional synthetic routes for SNAC and related salicylate amide compounds, including ester-based approaches. US’242 teaches:
Preparation of salicylic-acid-derived amides of amino-fatty acids using ester intermediates and subsequent hydrolysis/salt formation (see US’242, col. 2, ll. 20–55; col. 3, ll. 1–40).
Use of lower alkyl salicylate esters (e.g., methyl or ethyl esters) as known equivalents to free salicylic acid for forming the amide linkage (see col. 3, ll. 15–35).
Formation of sodium salts of the resulting amide acids using sodium hydroxide (see col. 4, ll. 10–30; Example 1A).
US’242 therefore teaches that O-alkyl salicylate esters are predictable substitutes for free salicylic acid in SNAC-type synthesis, corresponding to X = O-alkyl as recited in claim 1 and dependent claims 4–5.
US’386 discloses salicylate-amino fatty acid amide compounds, including N-(8-[2-hydroxybenzoyl]amino)caprylic acid and its salts, and their pharmaceutical use. US’386 teaches:
The compound N-(8-[2-hydroxybenzoyl]amino)caprylic acid (NAC) and alkali metal salts, including sodium salts (see US’386, col. 7, ll. 5–35; claims 1–3).
That such compounds are suitable for pharmaceutical compositions, including solid dosage forms (see col. 9, ll. 1–40; Example 6).
Conventional formulation of NAC/SNAC into solid pharmaceutical compositions using known excipients and processing steps (see col. 10, ll. 10–45).
US’386 therefore supports claims 11–15, which are directed to producing SNAC and preparing solid pharmaceutical compositions comprising SNAC.
It would have been obvious to a person of ordinary skill in the art to combine the teachings of US’833 with US’242 because both references address manufacture of NAC/SNAC, and US’242 expressly teaches that salicylic acid esters (e.g., methyl or ethyl esters) are known, predictable alternatives to free salicylic acid for amide formation (US’242, col. 3, ll. 15–35). Substituting an esterified salicylate in the process of US’833 represents a routine optimization using known equivalents.
It further would have been obvious to apply the pharmaceutical teachings of US’386 to the SNAC produced by the combined processes of US’833 and US’242, because US’386 teaches that SNAC is a known active agent suitable for formulation into solid pharmaceutical compositions using conventional techniques.
Claims 2–5 limit R¹, R², and X to hydrogen, alkali metal cations, or lower alkyl esters (methyl or ethyl).
US’833 teaches alkali metal salts (col. 6, ll. 5–25).
US’242 teaches methyl and ethyl salicylate esters (col. 3, ll. 15–35).Selection among these known options constitutes a routine design choice.
Claims 6–8 recite specific intermediates and 8-[(2-hydroxybenzoyl) amino] octanoate compounds.
US’833 teaches formation of NAC and isolation of its salts (Examples 3–4).These compounds are predictable products of the disclosed processes.
Claims 9 and 10 specify batch or continuous processing.
None of the references limit the reactions to a specific processing mode.The choice between batch and continuous operation is a matter of scale-up and equipment selection, which would have been obvious.
Claims 11–13 recite producing SNAC.
US’833 teaches SNAC formation (Example 4).
US’242 teaches sodium salt formation via neutralization (col. 4, ll. 10–30).
Claims 14 and 15 recite producing solid pharmaceutical compositions comprising SNAC.
US’386 teaches formulation of SNAC into solid pharmaceutical compositions (col. 9, ll. 1–40; col. 10, ll. 10–45).
The combined teachings of US’833, US’242, and US’386 disclose all limitations of claims 1–19, and any differences between the claimed subject matter and the prior art represent predictable substitutions, routine processing choices, and conventional formulation steps.
Claim 16 depends from claim 2 and further limits the method such that R2 is hydrogen or K⁺. As discussed above with respect to independent claim 1 and dependent claims 2–5, US’833 teaches preparation of the free acid form of N-(8-[2-hydroxybenzoyl]amino)caprylic acid and conversion of the free acid to alkali metal salts, including potassium salts, by neutralization with base (see US’833, col. 6, ll. 5–25; Examples 3–4). US’242 similarly teaches routine interconversion between free acids and alkali metal salts of salicylate amide compounds (see US’242, col. 4, ll. 10–30).
Accordingly, limiting R2 to hydrogen or K⁺ represents a routine selection among explicitly taught and interchangeable forms and does not impart patentable distinction. Claim 16 is therefore obvious for the same reasons as claims 1–5.
Claim 17 further limits claim 5 such that X is O-methyl. As set forth above, US’242 explicitly teaches the use of lower alkyl salicylate esters, including methyl salicylate, as known and conventional reactants for forming salicylic-acid-derived amides (see US’242, col. 3, ll. 15–35). US’833 teaches amide formation from salicylate derivatives without excluding methyl esters (see US’833, col. 5, ll. 10–40).
Selection of O-methyl from within the broader class of O-alkyl esters taught by the references constitutes a species selection within a taught genus and represents a predictable substitution. Claim 17 is therefore obvious.
Claims 18 and 19 depend from claim 13 and recite that the method is performed in batch mode (claim 18) or as a continuous process (claim 19). As discussed above with respect to claims 9 and 10, none of US’833, US’242, or US’386 limit the disclosed reactions to a particular mode of operation. The choice between batch processing and continuous processing is a matter of manufacturing scale, equipment configuration, and process optimization, which is routinely within the level of ordinary skill in the art.
Absent recitation of specific operating parameters or demonstration of a technical effect attributable to the selected processing mode, the choice of batch or continuous operation does not impart patentable distinction. Claims 18 and 19 are therefore obvious.
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, 4-5 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, 4, and 5 are rejected under 35 U.S.C. §112(b) as being indefinite, because the term “O-alkyl” lacks a clear and definite scope.
Claim 1 defines substituent X as “selected from O-alkyl, O-phenyl, O-benzyl, and N-hydroxysuccinimide (NHS).” The term “O-alkyl” is not limited by carbon number or otherwise defined in the claims. Elsewhere, the claims expressly limit alkyl groups to C1–C6 alkyl, creating internal inconsistency and uncertainty as to the intended scope of “O-alkyl.”
Because “O-alkyl” could reasonably encompass alkyl groups of widely varying chain length and chemical properties, the scope of the claims is unclear.
Accordingly, claims 1, 4, and 5 are indefinite.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DEBORAH D CARR whose telephone number is (571)272-0637. The examiner can normally be reached Monday-Friday (10:30 am -6:30 pm).
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/DEBORAH D CARR/Primary Examiner, Art Unit 1691