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
DETAILED ACTION
1. Original claims 1-18 filed 12/1/23 are acknowledged.
2. Priority
Receipt is acknowledged of papers (foreign priority filed 10/28/22) submitted under 35 U.S.C. 119(a)-(d), which papers have been placed of record in the file.
3. IDS(s) filed 12/1/23, 12/19/24 & 2/24/25 are acknowledged. Signed copies of the IDS(s) are provided with this Office Action.
4. Drawings
The drawings filed on 12/1/23 are acknowledged.
5. Specification
The specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant's cooperation is requested in correcting any errors of which applicant may become aware in the specification.
6. Claims 1-18 are drawn to as follows:
1. A liquid formulation comprising botulinum toxin and proline.
2. The liquid formulation of claim 1, wherein the botulinum toxin is botulinum toxin type A.
3. The liquid formulation of claim 1, wherein the proline is included at a concentration of 0.01% (w/v) to 0.5% (w/v), based on the total liquid formulation.
4. The liquid formulation of claim 1, further comprising sucrose.
5. The liquid formulation of claim 4, wherein the sucrose is included at a concentration of 0.5% (w/v) to 20% (w/v), based on the total liquid formulation.
6. The liquid formulation of claim 1, further comprising albumin.
7. The liquid formulation of claim 6, wherein the albumin is recombinant albumin.
8. The liquid formulation of claim 6, wherein the albumin is included at a concentration of 0.01% (w/v) to 1% (w/v), based on the total liquid formulation.
9. The liquid formulation of claim 1, further comprising a non-ionic surfactant and an isotonic agent.
10. The liquid formulation of claim 9, wherein the non-ionic surfactant is one or more selected from the group consisting of polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, and polysorbate 100.
11. The liquid formulation of claim 1, further comprising a non-ionic surfactant at a concentration of 0.005% (w/v) to 0.1% (w/v).
12. The liquid formulation of claim 9, wherein the isotonic agent is one or more selected from the group consisting of sodium chloride, glycerin, potassium chloride, and dextrose.
13. The liquid formulation of claim 1, comprising 100 units/mL botulinum toxin; and 0.01% (w/v) to 0.5% (w/v) proline.
14. The liquid formulation of claim 1, comprising 100 units/mL botulinum toxin; 0.01% (w/v) to 0.5% (w/v) proline; and 0.01% (w/v) to 1% (w/v) albumin.
15. The liquid formulation of claim 1, comprising 100 units/mL botulinum toxin; 0.01% (w/v) to 0.5% (w/v) proline; and 0.5% (w/v) to 20% (w/v) sucrose.
16. The liquid formulation of claim 1, comprising 100 units/ml botulinum toxin; 0.01% (w/v) to 0.5% (w/v) proline; 0.01% (w/v) to 1% (w/v) albumin; and 0.5% (w/v) to 20% (w/v) sucrose.
17. A method of stabilizing botulinum toxin using a liquid formulation including botulinum toxin and proline.
18. The method of claim 17, wherein albumin, sucrose, or both albumin and sucrose is/are further included in the liquid formulation.
7. 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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 1-3 & 17 is/are rejected under 35 U.S.C. 102(a)(1)/(a)(2) as being anticipated by KR 10-1744900 Bl (DAEWOONG CO., LTD.) 08 June 2017. KR 10-1744900 B1 teaches a liquid composition or a method of stabilizing botulinum toxin using a liquid formulation including botulinum toxin and proline comprising botulinum toxin type A and L-proline; the stabilization of the botulinum toxin using L-proline as a stabilizer; and L-proline content of 0.223 w/v % in the liquid composition (see example 2). The reference also indicates the addition of sucrose, albumin, a nonionic surfactant, and an isotonic agent (see paragraphs [0029], [0045], and example 1). The reference anticipates the claims.
8. 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim(s) 4-16 & 18 is/are rejected under 35 U.S.C. 103 as being unpatentable over KR 10-1744900 B1 in view of US 20230165946 A1.
The teachings of KR 10-1744900 B1 are described above in paragraph 7.
US 20230165946 A1 teaches for example in paragraph [0049] that The botulinum toxin liquid preparation may not contain any animal component. The botulinum toxin liquid preparation may not include albumin, a deficiency taught in the teachings of KR 10-1744900 B1.
US 20230165946 A1 teaches for example, the botulinum toxin liquid preparation may include botulinum toxin, amino acids, surfactants, and a tonicity adjuster in water. For example, the botulinum toxin liquid preparation may include 10 U/mL to 70 U/mL of botulinum toxin, 0.05 g/L to 0.7 g/L of amino acids, and 0.10 g/L to 0.5 g/L of surfactants, and 0.10 g/L to 1.0 g/L of NaCl in water. The botulinum toxin may be botulinum toxin types A, B, C1, C2, D, E, F, G, or a mixture thereof. The amino acid may be glycine, alanine, valine, leucine, isoleucine, proline, phenylalanine, tyrosine, tryptophan, serine, threonine, cysteine, methionine, asparagine, glutamine, lysine, arginine, histidine, aspartic acid, glutamic acid, a pharmaceutically acceptable salt thereof, or a mixture thereof. The amino acid may be, for example, methionine, histidine, arginine, a pharmaceutically acceptable salt thereof, or a mixture thereof. The surfactant may be a nonionic surfactant. The nonionic surfactant may be polysorbate, poloxamer, or a mixture thereof. The polysorbate may be polysorbate 20, polysorbate 40, polysorbate 60, polysorbate 80, or a mixture thereof. The NaCl may be added at a physiologically acceptable concentration, for example, from about 0.85 g/L to 0.95 g/L, or about 0.9 g/L. See paragraph [0048-0049]. Tables 9-10 show the addition of Human serum albumin, while in other cases albumin was not included.
Claims 4-16 describe adding sucrose, albumin, a nonionic surfactant, and an isotonic agent, or delimit the concentration of sucrose, the type and concentration of albumin, the nonionic surfactant, and the isotonic agent, and the concentration of the botulinum toxin and proline. However, such delimitation is not considered to
have any special technical significance, and KR 10-1744900 B1 also indicates the addition of sucrose, albumin, a nonionic surfactant, and an isotonic agent (see paragraphs [0029], [0045], and example 1). Other delimitations could also be easily derived or optimized to the desired concentration(s) by a person skilled in the art by means of repeated experimentation, through simple addition or selection, for achieving the desired effect. Claim 18 describes adding sucrose and albumin, but KR 10-1744900 B1 also indicates that sucrose or albumin may be added (see paragraphs [0029] and [0045]). A person skilled in the art could easily derive the feature by means of repeated experimentation, through simple addition or selection, to achieve the desired effect, and the effect thus achieved could also be predicted.
It would have been obvious before the effective filing date of the claimed invention for one of ordinary skill in the art of enzymology/general biology to combine the teachings of KR 10-1744900 B1 and US 20230165946 A1 and optimize the liquid formulation and comprising botulinum toxin - type A and proline and varying levels of sucrose, the type and concentration of albumin, the nonionic surfactant, and the isotonic agent, and the concentration of the botulinum toxin, proline, and other components of the liquid formulation, and do so with a reasonable expectation of success. One skilled in the art would have been motivated in view of the importance of [§0002 in US 20230165946 A1] Botulinum toxin (BoNT) as one of the most powerful toxins known and acts by blocking the release of acetylcholine in peripheral cholinergic neurons. Botulinum toxin is administered to individuals in very small doses, to reduce overactive muscles and hyperactive exocrine glands. For example, botulinum toxin is being used for cosmetic purposes as well as for the treatment of neuromuscular diseases and hyperactive exocrine gland diseases as noted in the teachings of US 20230165946 A1, See paragraph [0002].
Thus, the claimed invention was within the ordinary skill in the art to make and use at the time was made and was as a whole, prima facie obvious.
9. No claim is allowed.
10. US20250092378A1 is publication number of the instant application.
11. Any inquiry concerning this communication or earlier communications from the examiner should be directed to TEKCHAND SAIDHA whose telephone number is (571)272-0940. The examiner can normally be reached on M-F 8.00-5.30. Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Robert B Mondesi can be reached on 408 918 7584. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300. Information regarding the status of an application may be obtained from the Patent Application Information Retrieval (PAIR) system. Status information for published applications may be obtained from either Private PAIR or Public PAIR. Status information for unpublished applications is available through Private PAIR only. For more information about the PAIR system, see http://pair-direct.uspto.gov. Should you have questions on access to the Private PAIR system, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative or access to the automated information system, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/TEKCHAND SAIDHA/
Primary Examiner, Art Unit 1652
Recombinant Enzymes, Hoteling
Telephone: (571) 272-0940
Fax: (571) 273-0940