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 .
Election/Restrictions
Applicant's election with traverse of the species: SEQ ID NO: 45 (claim 2), SEQ ID NO: 3 (claim 3), serotype A (claim 5), and an amino terminus (claim 6) in the reply filed on 04/14/2026 is acknowledged. The traversal is on the ground(s) that the invention is based on the common technical feature of “a technique for treating alopecia using a botulinum toxin recombinant protein in which a cell-penetrating peptide is fused to a botulinum toxin light chain” and this feature is equally applicable to all species included in the Markush group. This is not found persuasive because for SEQ ID NOs: 3 and 45, the alternatives within the Markush group do not share a common sequence; for the botulinum toxin serotypes, the alternatives within the Markush group do not share a common structure and/or mechanism of action; and for the fusion of the cell-penetrating peptide, the alternatives with the Markush group do not share a common structure. Therefore, the species lack the same or corresponding technical features and do not relate to a single general inventive concept under PCT Rule 13.1.
The requirement is still deemed proper and is therefore made FINAL.
Priority
The instant application filed on 04/22/2024 is a 371 of PCT/KR2022/009761 filed on 07/06/2022 and claims priority to KR10-2021-0141684 filed on 10/22/2021 and KR10-2022-0079197 filed on 06/28/2022. The certified priority documents for KR10-2021-0141684 and KR10-2022-0079197 are not in English; therefore the effective filing date of the instantly claimed invention is 07/06/2022.
Should applicant desire to obtain the benefit of foreign priority under 35 U.S.C. 119(a)-(d) prior to declaration of an interference, a certified English translation of the foreign application must be submitted in reply to this action. 37 CFR 41.154(b) and 41.202(e).
Failure to provide a certified translation may result in no benefit being accorded for the non-English application.
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 07/17/2024 is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Drawing Objections
The drawings are objected to because higher quality images are requested for Figures 8-11. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Claim Rejections - 35 USC § 103, Obviousness
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.
Claims 1-11 and 18 are rejected under 35 U.S.C. 103 as being unpatentable over Lee (US 2017/0246266; Date of Publication: August 31, 2017) in view of Schwartz (U.S. Patent No. 6,299,893; Date of Publication: October 9, 2001).
Lee’s general disclosure relates to “a novel cell penetrating peptide; a cell penetrating botulinum toxin recombinant protein composition in which the cell penetrating peptide and the light chain of a botulinum toxin are fused; and a use thereof and, more specifically, to a composition enabling the transdermal delivery of a cell penetrating botulinum toxin recombinant protein and capable of being locally used for various treatments of the skin and cosmetic purposes. The cell penetrating peptide-botulinum toxin recombinant protein of the present invention can be transdermally delivered, thereby having the intrinsic effect of a botulinum toxin and simultaneously having greater convenience of use, and thus can be effectively applied as a local agonist for the treatment of various diseases and aesthetic and/or cosmetic purposes” (see, e.g., Lee, abstract).
Regarding claim 1 pertaining to a composition comprising a botulinum toxin recombinant protein, Lee teaches a botulinum toxin recombinant protein (see, e.g., Lee, abstract), wherein a “cell penetrating peptide and the light chain of a botulinum toxin are fused” (see, e.g., Lee, abstract). Moreover, Lee teaches SEQ ID NO: 1, which is the cell penetrating peptide, and which has 100% sequence identity to instant SEQ ID NO: 1 (see, e.g., Lee, [0016] & Office Action Appendix). Lee teaches “The present invention provides a cell-penetrating botulinum toxin recombinant protein in which the cell-penetrating peptide consisting of the amino acid sequence of SEQ. ID. NO: 1 is conjugated with one or both termini of the light chain of botulinum toxin” (see, e.g., Lee, [0019]). Regarding the therapeutically effective amount, Lee teaches 2.5 µM, 5 µM, and 10 µM of the botulinum recombinant protein exhibits “excellent cell penetration potential in keratinocytes” (see, e.g., Lee, Example 2, [0122]). Furthermore, Lee teaches “an amount of a light chain or light chain derivative of skin-penetrating and a nerve terminus cell-penetrating botulinum toxin, which is sought in the present invention, should be limited to a concentration of 1 to 10 ppm in order to ensure safety” (see, e.g., Lee, [0011]); therefore, one of ordinary skill in the art would be motivated to test and use the botulinum toxin recombinant protein at a concentration between 1 to 10 ppm, or below 1 ppm, in order to ensure safety, while also testing for hair growth.
Regarding claim 2 pertaining to the botulinum toxin recombinant protein, Lee teaches SEQ ID NO: 45, which encodes for the botulinum toxin recombinant protein, and which has 100% sequence identity to instant SEQ ID NO: 45 (see, e.g., Lee, [0020] & Office Action Appendix).
Regarding claim 3 pertaining to the botulinum toxin light chain, Lee teaches SEQ ID NO: 38, which has 100% sequence identity to instant SEQ ID NO: 3 (see, e.g., Lee, [0020] & Office Action Appendix).
Regarding claim 4 pertaining to the botulinum toxin light chain having a hexahistidine tag, Lee teaches “the light chain of botulinum toxin may further comprise a hexahistidine tag at one terminus” (see, e.g., Lee, [0022]).
Regarding claim 5 pertaining to the botulinum toxin light chain serotype, Lee teaches “the light chain of botulinum toxin may be selected from the group consisting of botulinum toxin serotypes A, B, C, D, E, F and G” (see, e.g., Lee, [0023]).
Regarding claim 6 pertaining to fusion of the cell-penetrating peptide, Lee teaches “the conjugation may be conjugation of the cell-penetrating peptide to a carboxyl terminus or an amino terminus of the light chain of botulinum toxin, or both termini thereof” (see, e.g., Lee, [0024]).
Regarding claim 7 pertaining to the bond for the fusion, Lee teaches “the conjugation may be achieved by a peptide bond or a covalent bond” (see, e.g., Lee, [0025]).
Regarding claims 8-10 pertaining to the composition promoting different effects, Lee teaches the same composition (see, e.g., Lee, abstract), [0016], [0019], [0020], and [0022]-[0024]), as well as administration of the same composition (see, e.g., Lee, [0032]), which would inherently result in proliferation of dermal papilla cells, promotion of prostaglandin F2α expression, promotion of hair growth, and reduction in alopecia.
Regarding claim 11 pertaining to transdermal administration, Lee teaches “the pharmaceutical composition may be used for transdermal administration” (see, e.g., Lee, [0032]).
Regarding claim 18 pertaining to the composition, Lee teaches that the composition may be a cosmetic composition used for dermatological treatments and cosmetological purposes (see, e.g., Lee, [0014]). Lee also teaches that the composition is a pharmaceutical composition that can be used to treat facial spasms, eyelid spasms, torticollis, blepharospasm, cervical dystonia, oropharynx dystonia, spasmodic dysphonia, migraines, and hyperhidrosis (see, e.g., Lee, [0031]).
However, Lee does not teach: a therapeutically effective amount for the treatment of alopecia (claim 1); or administration to a subject in need thereof (i.e., a subject with alopecia) (claim 1).
Schwartz’s general disclosure relates to “a method for reduction of hair loss and stimulation of hair growth on the scalp of a human patient. The method comprises the step of administering a presynaptic neurotoxin into the scalp of the patient in a quantity and concentration to provide a therapeutically-effective flaccid paralysis of the muscle tissue outside of the skull of the patient. The result is a reduction in tissue tension in the desired area of hair-growth without affecting any tissue not outside the skull of the patient” (see, e.g., Schwartz, abstract).
Regarding claim 1 pertaining to administration of a therapeutically effective amount to a subject with alopecia, Schwartz teaches “a method of treating the scalp to reduce hair loss and stimulate hair growth on the scalp” (see, e.g., Schwartz, col 1, lines 5-7), wherein the method comprises administration of a presynaptic neurotoxin, such as botulinum toxin A (see, e.g., Schwartz, col 1, lines 65-66 & col 2, lines 40-41), to a subject in need of hair growth (see, e.g., Schwartz, col 1, lines 63-64 & col 4, lines 41-45). Moreover, Schwartz teaches administration of 0.1 ml of botulinum toxin diluted to 10 units per 0.1 ml to a patient’s scalp (see, e.g., Schwartz, col 3, lines 44-46). More specifically, Schwartz teaches a case study wherein “A healthy 39 year old non-smoker with Hamilton class V male pattern baldness was injected intramuscularly with 100 units BTX-A diluted to 10 units per 0.1 ml in normal saline. The frontal, temporal, peri-auricular and occipital muscles were injected with a fine gauge hypodermic needle in a circumferential manner around the periphery of the scalp as described above. The vertex was photographed as well, position of frontal sentinel hairs and average daily hair loss collected in a fine toothed comb. At 6 months scalp tension increased and a further 100 unite of botulinum toxin A was injected in a manner similar to the first injection. At 1 year, post treatment, daily hair loss was reduced by 76 percent and the frontal sentinel hair was 1 cm forward of its predecessor” (see, e.g., Schwartz, col 4, lines 41-55).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to produce Lee’s botulinum toxin recombinant protein, wherein the protein is administered to treat hair loss in patients, as taught by Schwartz. One would have been motivated to do so because Schwartz teaches “The inventors have found that injection of a presynaptic neurotoxin improves the tissue environment surrounding the hair follicles by reducing scalp tension and, by doing so, improves bloodflow through the arteries. In turn, the tension in hair-bearing tissue is reduce and hair growth is stimulated” (see, e.g., Schwartz, col 4, lines 35-40). Moreover, Lee teaches that the cell penetrating peptide is “capable of mediating intracellular delivery of a biologically active molecule, wherein the cell-penetrating peptide is designed to effectively transmit a botulinum toxin protein which is difficult to be delivered through the skin because of a molecular weight and the intrinsic characteristics of a skin cornified layer” (see, e.g., Lee, [0012]). Additionally, Lee teaches “the cell-penetrating peptide itself may not have a defined enzymatic or biological therapeutic activity, but serves as a carrier facilitating intracellular transduction through the cell membrane” (see, e.g., Lee, [0085]). Therefore, based on the teachings of Lee and Schwartz, it would be obvious to produce the Lee’s botulinum toxin recombinant protein for treatment of hair loss, as taught by Schwartz, because then the recombinant protein can be effectively delivered into the skin of the scalp of a patient in order to stimulate hair growth. One would have expected success Lee and Schwartz both teach administration of botulinum toxin for cosmetic purposes.
Conclusion
Claims 1-11 and 18 are rejected.
No claims are allowed.
Correspondence Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to NATALIE IANNUZO whose telephone number is (703)756-5559. The examiner can normally be reached Mon - Fri: 8:30-6:00 EST.
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/NATALIE IANNUZO/Examiner, Art Unit 1653
/SHARMILA G LANDAU/Supervisory Patent Examiner, Art Unit 1653
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