Notice of Pre-AIA or AIA Status
The present application is being examined under the pre-AIA first to invent provisions.
DETAILED ACTION
1. Applicant’s response filed on February 12, 2026 is acknowledged. Claims 1, 2, 6, 7, 9-12, 16, 17, and 19-34 are currently pending. Claims 1, 6, 7, 9-11, 16, 17, 19-21 and 25 have been amended. Claim 8 has been canceled. Claims 26-34 have been added. Claims 11-12, 16, 17 and 19-21 were previously withdrawn without traverse. In view of said amendments, claims 28-30, 32 and 34 are also withdrawn from consideration as being drawn to an invention that has been withdrawn without traverse. Claims 1, 2, 6, 7, 9,10, 22-27, 31 and 33 are currently under examination.
Priority
2. In view of Applicant’s amendment to the claims, the claims are now supported by PCT/US09/69576 and PRO 61/142,063. Thus moving forward, Applicant is afforded a filing date of 12/31/2008.
Objections Withdrawn
3. In view of Applicant’s amendment, the objection to the application for failing to comply with the requirements of 37 C.F.R. 1.821-1.825 because it contains amino acid sequences with 4 or more specifically defined and enumerated residues is withdrawn.
4. In view of Applicant’s amendment, the objection to claim 1 for reciting a specifically defined sequence which must be identified is withdrawn.
5. In view of Applicant’s amendment, the objection to claim 8 for using a trademark to identify the instant invention is withdrawn.
Rejections Withdrawn
6. In view of Applicant’s amendments, the rejection of claims 1, 2, 6-10, 16, 17, and 22-25 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn.
New Grounds of Rejection Necessitated by Amendment
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.
7. Claims 1 and 25-27 recites the limitation "wherein Kn has a molecular weight…." in line 1 of claim 25. There is insufficient antecedent basis for this limitation in the claim.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of pre-AIA 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 –
(e) the invention was described in (1) an application for patent, published under section 122(b), by another filed in the United States before the invention by the applicant for patent or (2) a patent granted on an application for patent by another filed in the United States before the invention by the applicant for patent, except that an international application filed under the treaty defined in section 351(a) shall have the effects for purposes of this subsection of an application filed in the United States only if the international application designated the United States and was published under Article 21(2) of such treaty in the English language.
8. Claim(s) 1, 2, 6, 7, 9, 10, 22-24, 31 and 33 are rejected under pre-AIA 35 U.S.C. 102(e) as being anticipated by Waugh et al., US20040220100A1.
Independent claim 1 is drawn to a method of administering botulinum toxin to achieve a
therapeutic or cosmetic effect to an individual in need thereof, the method comprising
injecting an effective amount of a composition into the individual to achieve a
therapeutic or cosmetic effect, wherein the composition comprises a positively charged carrier with a polylysine backbone covalently attached to an efficiency group at an N-terminus of the polylysine backbone and an efficiency group at the C-terminus of the polylysine backbone, wherein the efficiency groups have the formula (gly)ₚ-YGRKKRRQRRR- (gly)q (SEQ ID NO: 4) or (SEQ ID NO: 7) and each efficiency group is covalently attached to the polylysine
backbone via the C-terminus or the N-terminus of the efficiency group, wherein the polylysine backbone has a molecular weight of about 500 D to about 5000 D and wherein p is selected from 0 to 5, and q is selected from 0 to 5, a botulinum toxin component selected from botulinum toxin complex, reduced botulinum toxin complex, and botulinum toxin, and wherein the positively charged carrier is non-covalently associated with the botulinum toxin complex, reduced botulinum toxin complex, or botulinum toxin.
Waugh discloses administration of botulinum toxin may also be carried out to treat other conditions, including treating of neurologic pain, prevention or reduction of migraine headache or other headache pain, prevention or reduction of acne, prevention or reduction of dystonia or dystonic contractions whether subjective or clinical, prevention or reduction of symptoms associated with subjective or clinical hyperhidrosis, reducing hypersecretion or sweating, reducing or enhancing immune response, or treatment of other conditions for which administration of botulinum toxin by injection has been suggested or performed (the Office takes the position that these conditions encompasses wrinkles as required by claim 9).The botulinum toxin is a suitable cosmeceutical agent and includes serotype A (see paragraph 0120; meets claims 33)
Administration of botulinum toxin and other antigens useful for immunization described herein, or other non-nucleic acid non-protein therapeutic agents for instance, the complexed botulinum toxin, may also be carried out for immunization-related purposes. Alternately, the complex can be prepared and applied topically to enhance an immune response, for example to provide immunizations respecting various proteins, for example, for childhood immunizations without injections or immunization against various environmental hazards. Surprisingly, administration of botulinum toxin or other therapeutic proteins, described herein may also be carried out to reduce immune response (see paragraph 0136; meets claim 10, 31). Additionally, Waugh discloses that their formulations are suitable for parenteral administration, such as, for example, by intravenous, intramuscular, intradermal, and subcutaneous routes, include aqueous and non-aqueous, isotonic sterile injection solutions, which can contain antioxidants, buffers, bacteriostats, and solutes that render the formulation isotonic with the blood of the intended recipient, and aqueous and non-aqueous sterile suspensions that can include suspending agents, solubilizers, thickening agents, stabilizers, and preservatives (see paragraph 0169, meets claim 1).
In a particularly preferred embodiment, the positively charged backbone is a polypeptide having branching groups (also referred to as efficiency groups) independently selected from -(gly) n1-(arg)n2, HIV-TAT or fragments thereof, or the protein transduction domain of Antennapedia, or a fragment or mixture thereof, in which the subscript n1 is an integer of from 0 to 20, more preferably 0 to 8, still more preferably 2 to 5, and the subscript n2 is independently an odd integer of from about 5 to about 25, more preferably about 7 to about 17, most preferably about 7 to about 13. Still further preferred are those embodiments in which the HIV-TAT fragment has the formula (gly)p-RGRDDRRQRRR-(gly)q, (gly)p-YGRKKRRQRRR-(gly)q or (gly)p-RKKRRQRRR-(gly)q wherein the subscripts p and q are each independently an integer of from 0 to 20 and the fragment is attached to the backbone via either the C-terminus or the N-terminus of the fragment. Preferred HIV-TAT fragments are those in which the subscripts p and q are each independently integers of from 0 to 8, more preferably 2 to 5. In another preferred embodiment the positively charged side chain or branching group is the Antennapedia (Antp) protein transduction domain (PTD), or a fragment thereof that retains activity (see paragraph 0083; meets claim 1, 22-24). In general, the compositions are prepared by mixing the insulin, botulinum toxin, or other biologically active agent such as for example, a therapeutic protein which does not therapeutically alter blood glucose levels, a therapeutic nucleic acid-based agent, a non-protein non-nucleic acid therapeutic agent or alternately an agent for immunization to be administered with the positively charged carrier, and usually with one or more additional pharmaceutically acceptable carriers or excipients. In their simplest form they may contain a simple aqueous pharmaceutically acceptable carrier or diluent, such as saline, which may be buffered. However, the compositions may contain other ingredients typical in topical pharmaceutical or cosmeceutical compositions, that is, a dermatologically or pharmaceutically acceptable carrier, vehicle or medium, i.e. a carrier, vehicle or medium that is compatible with the tissues to which they will be applied. The term “dermatologically or pharmaceutically acceptable,” as used herein, means that the compositions or components thereof so described are suitable for use in contact with these tissues or for use in patients in general without undue toxicity, incompatibility, instability, allergic response, and the like. As appropriate, compositions of the invention may comprise any ingredient conventionally used in the fields under consideration, and particularly in cosmetics and dermatology. In all aspects of the present invention, the association between the carrier and the biologically active agent is by non-covalent interaction, which can include, for example, ionic interactions, hydrogen bonding, van der Waals forces, or combinations thereof (see paragraph 0137).
In yet another aspect, this invention relates to a composition comprising a biologically active agent such as botulinum toxin, and a carrier comprising a positively charged carrier having a backbone with attached positively charged branching or “efficiency” groups. Moreover, agents that have a biological activity or a therapeutic effect by binding a specific antigen, thereby blocking ligand binding or altering the conformation of the antigen are included in this invention. The biologically active agent is preferably botulinum toxin (BTX), an antigen for immunization, or certain antifungal agents. Most preferably the positively charged carrier is a comparatively short- or medium-chain positively charged polypeptide or a positively charged nonpeptidyl polymer, for example, a polyalkyleneimine. When the biologically active agent is botulinum toxin, the invention further relates to a method for producing a biologic effect such as muscle paralysis, reducing hypersecretion or sweating, treating neurologic pain or migraine headache, reducing muscle spasms, preventing or reducing acne, or reducing or enhancing an immune response, by topically applying a composition containing an effective amount of botulinum toxin, preferably to the skin, of a subject or patient in need of such treatment (meets claim 1, 2, 10, 31, 33). However, carriers of this invention that have a positively charged backbone with positively charged branching groups, as described herein are quite surprisingly capable of providing transdermal delivery of botulinum toxin (see paragraph 0043).
Waugh discloses 100 % sequence identity to SEQ ID NO: 4; see attached SCV results:
SEQ ID NO:4
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226
387
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118
473
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The positively-charged backbone (also referred to as a positively charged “carrier”) is typically a linear chain of atoms, either with groups in the chain carrying a positive charge at physiological pH, or with groups carrying a positive charge attached to side chains extending from the backbone. Preferably, the positively charged backbone itself will not have a defined enzymatic or biologic activity. Additionally, the backbone will often be a polymer of repeating units. In one group of embodiments, the positively charged backbone is a polypropyleneamine wherein a number of the amine nitrogen atoms are present as ammonium groups (tetra-substituted) carrying a positive charge (see paragraph 0078).
As it pertains to claim 6, the method steps are identical and thus the formulation is necessarily such that the positively charged carrier stabilizes botulinum toxin against degradation; as well as necessarily reduces local diffusion of botulinum toxin following injection, as recited in claim 7.
8. No claim is allowed.
9. Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
10. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LAKIA J JACKSON-TONGUE whose telephone number is (571)272-2921. The examiner can normally be reached Monday-Friday 930AM-530PM.
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, Gary B Nickol can be reached at 571-272-0835. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/LAKIA J JACKSON-TONGUE/Examiner, Art Unit 1645 June 12, 2026
/BRIAN GANGLE/Primary Examiner, Art Unit 1645
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