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 .
The preliminary amendment filed on 1/4/2024 is acknowledged. Claims 9 and 11 are amended. Claims 10 and 17-18 are cancelled. Claims 1-9 and 11-16 are pending and are currently under examination.
Information Disclosure Statement
The information disclosure statement filed on 1/5/2024 has been considered. A signed copy is enclosed.
Specification
The use of the trademark SEPHAROSE has been noted in this application on pages 15-17. It should be capitalized wherever it appears and be accompanied by the generic terminology.
Although the use of trademarks is permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as trademarks.
It is noted that the cited occurrence of improper use is only exemplary and applicant should review the specification to correct any other use of trademarks.
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 2 and 7 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 pre-AIA the applicant regards as the invention.
Claims 2 and 7 are rendered indefinite by the recitation of the trademark SEPHAROSE. If a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of the 35 U.S.C. 112, second paragraph. Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product.
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.
Claim 14 is rejected under 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 14 requires that step (c) is dissociating the toxin protein into a non-toxic protein and a pure neurotoxin protein. However, in the parent claim, step (c) requires obtaining the non-complex neurotoxin protein from the toxin protein. This can only happen by dissociating the toxin protein into a non-toxic protein and a pure neurotoxin protein. Therefore, claim 14 does not further limit the parent claim. 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 § 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.
Claims 1-9 and 11-16 are rejected under 35 U.S.C. 103 as being unpatentable over Ruegg et al (US Patent Application Publication 2011/0092682; IDS filed 1/5/2024) in view of Kim et al (WO2015/016462).
The instant claims are drawn to methods of purifying a non-complex C. botulinum neurotoxin protein.
Ruegg et al disclose methods of purifying non-complexed botulinum toxin starting with culturing C botulinum followed by acid precipitation to pH 3.5 then filtration to collect the precipitate (see paragraph 0079). The filtrate is then loaded into phenyl Sepharose HP hydrophobic interaction column to capture the toxin (see paragraph 0079). The toxin is eluted using a concentration gradient (see paragraph 0079). The toxin is then diluted into a phosphate buffer to dissociate the toxin complex and then added to an anion exchange column, eluted and the non-complexed neurotoxin is captured (see paragraph 0079). A cation exchange column is not used (see paragraph 0079). The purity of the toxin is at least 99% (see paragraph 0066). Botulinum toxin type A is 150kD (see claim 9).
Ruegg et al differs from the instant invention in that, while they disclose the use of anion exchange chromatography, they do not disclose that it should specifically be a resin containing aa tertiary amine. Ruegg et al does state that any anion column known in the art to be suitable for separating charged proteins can be used (see paragraph 0056). Ruegg et al also discloses the use of DEAE resin (tertiary amine anion exchange resin) in purification of botulinum toxin (see paragraph 0078). Ruegg et al also does not specifically state that the conductivity in step (a) is 170mS/cm to 220 mS/cm and does not disclose acid precipitation using ammonium sulfate at a final saturation of 30% to 50% or dialysis using sodium phosphate buffer three times in step (c).
Kim et al disclose methods of purifying botulinum toxin using various acid precipitation and anion exchange chromatography steps. Kim et al disclose a step of acid precipitation prior to anion exchange chromatography using ammonium sulfate at 20-40% (see paragraph 91). Kim et al also state that the anion exchange resin is preferably DEAE, which is a tertiary amine group (see paragraph 43).
It would have been obvious to one of ordinary skill in the art, at the time of invention to use DEAE Sepharose resin in the anion exchange chromatography step of Ruegg et al because DEAE resin was known to be useful in purifying botulinum toxin (as evidenced by the teachings of both Ruegg et al and Kim et al) and because Ruegg et al state that any anion exchange resin can be used. It would have been obvious to use the conductivity recited in claim 8 because these are standard conditions used in hydrophobic interaction chromatography. Additionally, acid precipitation and dialysis purification steps are well known and widely used in the art in protein purification and in botulinum toxin purification.
One would have had a reasonable expectation of success because each of these steps is widely known and used, as evidenced by the teachings of both Ruegg et al and Kim et al and simply combining the steps would not make them unsuitable.
In addition, the selection of a known material based on its suitability for its intended use supported a prima facie obviousness determination in Sinclair & Carroll Co. v.Interchemical Corp., 325 U.S. 327, 65 USPQ 297 (1945) (Claims to a printing ink comprising a solvent having the vapor pressure characteristics of butyl carbitol so that the ink would not dry at room temperature but would dry quickly upon heating were held invalid over a reference teaching a printing ink made with a different solvent that was nonvolatile at room temperature but highly volatile when heated in view of an article which taught the desired boiling point and vapor pressure characteristics of a solvent for printing inks and a catalog teaching the boiling point and vapor pressure characteristics of butyl carbitol.)
See also In reLeshin, 277 F.2d 197, 125 USPQ 416 (CCPA 1960) (selection of a known plastic to make a container of a type made of plastics prior to the invention was held to be obvious); Ryco, Inc.v.Ag-Bag Corp., 857 F.2d 1418, 8 USPQ2d 1323 (Fed. Cir. 1988) (Claimed agricultural bagging machine, which differed from a prior art machine only in that the brake means were hydraulically operated rather than mechanically operated, was held to be obvious over the prior art machine in view of references which disclosed hydraulic brakes for performing the same function, albeit in a different environment.).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian J Gangle whose telephone number is (571)272-1181. The examiner can normally be reached M-F, 9-6:30.
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/BRIAN GANGLE/ Primary Examiner, Art Unit 1645