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 without traverse of Group 1 (claims 1-13, 16, and 21) in the reply filed on 7/23/2026 is acknowledged.
Claims 19 and 25-28 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected invention, there being no allowable generic or linking claim. Accordingly, claims 1-13, 16, and 21 have been examined on the merits.
Priority
The instant application is a national stage entry of PCT/KR2022/008798 (filed on 6/21/2022), which claims foreign priority under 35 U.S.C. 119(a)-(d) based on application KR10-2021-0083950 (filed on 6/28/2021). Certified copy of the foreign priority document is on file.
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).
Information Disclosure Statement
The information disclosure statements (IDSs) submitted on 12/28/2023, 3/31/2025, and 11/11/2025 are in compliance with the provisions of 37 C.F.R. 1.97. All references cited in these IDSs have been fully considered.
Drawings
The drawings are objected to because the text in Figure 1 is too small to read. 37 C.F.R. 1.84 section (p)(3) requires that “Numbers, letters, and reference characters must measure at least .32 cm. (1/8 inch) in height”, while section (l) states “All drawings must be made by a process which will give them satisfactory reproduction characteristics. Every line, number, and letter must be durable, clean, black (except for color drawings), sufficiently dense and dark, and uniformly thick and well-defined”. See MPEP § 608.02(V).
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.
In addition to Replacement Sheets containing the corrected drawing figure(s), applicant is required to submit a marked-up copy of each Replacement Sheet including annotations indicating the changes made to the previous version. The marked-up copy must be clearly labeled as “Annotated Sheets” and must be presented in the amendment or remarks section that explains the change(s) to the drawings. See 37 CFR 1.121(d)(1). Failure to timely submit the proposed drawing and marked-up copy will result in the abandonment of the application.
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.
Claims 1-13, 16, and 21 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claims 1 and 9 recite the limitation “wherein a sequence of a second domain of first, second, third, and fourth domains of a botulinum toxin type A light chain, other than botulinum toxin type A1, is substituted with a sequence of a second domain of botulinum toxin type A1 or a variant thereof”. Similarly, claim 2 requires “wherein a sequence of the fourth domain of the first, second, third, and fourth domains of the recombinant botulinum toxin type A light chain is further substituted with a sequence of a fourth domain of botulinum toxin type Al or a variant thereof”. Applicant defines the term “domain” to mean “a given protein sequence and its conserved portions of tertiary structure that may evolve, function and exist independently of the rest of the protein chain. Because domains are independently stable, domains may be domain swapped by genetic engineering between one protein and another to create a chimera protein” (first par., page 21 of specification).
These limitations are obscure because what is established in the art is that botulinum toxin has a catalytic domain (light chain), a translocation domain (N-terminal portion of the heavy chain), and a receptor-binding domain (C-terminal portion of the heavy chain). The catalytic domain or light chain of botulinum toxin is not known to harbor any domains. Hence, it is unclear which parts of the light chain are “the first domain”, “the second domain”, “the third domain”, and “the fourth domain”.
Review of the disclosure (last two par. in page 22, first three par. in page 23 of specification) indicates that applicant divided the sequences of botulinum toxin type A1 and A4 light chains into four parts and referred to them as “the first domain”, “the second domain”, “the third domain”, and “the fourth domain” as shown in Figures 1-2. Under the broadest reasonable interpretation consistent with applicant’s description (but without importing limitations from the specification into the claims), the term “domain” is interpreted to mean a region of the protein. Thus for the purpose of applying prior art, each of the designations “first domain”, “second domain”, “third domain”, and “fourth domain” can be any distinct, functional portion of botulinum toxin type A light chain and not limited to a particular amino acid sequence or function.
Claims 3-8, 10-13, 16, and 21 are also considered indefinite for depending on claim 1 or 9.
Claims 6-8 are rejected under 35 U.S.C. 112(b) as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 6 refers to “the botulinum toxin type A heavy chain”. There is insufficient antecedent basis for this limitation because the parent claim only recites “further comprises a botulinum toxin heavy chain” and does not specify said heavy chain to be of type A. Claims 7-8 are also indefinite for depending on claim 6.
Claim 6 is additionally deemed indefinite since it attempts to limit the botulinum toxin type A heavy chain as “botulinum toxin type A, B, C, D, E, F, or G”. The heavy chain is already defined as type A so it is confusing how it can also be of any other type.
In the interest of compact prosecution, the phrase “wherein the botulinum toxin type A heavy chain” in claims 6-8 is treated as if it recites “wherein the botulinum toxin heavy chain” (i.e. not type A).
Claim Rejections - 35 USC § 102
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.
Claims 1-13, 16, and 21 are rejected under 35 U.S.C. 102(a)(1)/102(a)(2) as being anticipated by Johnson et al. (Pub. No. US 2018/0193435 A1).
Johnson et al. discloses hybrid neurotoxins specifically botulinum toxins (BoNTs) with altered properties, a composition comprising the hybrid neurotoxins, and uses thereof (Abstract; par. [0007], [0013]).
In some embodiments, a hybrid BoNT comprises at least a portion of a light chain polypeptide from a first subtype and at least a portion of a heavy chain polypeptide from a second subtype. In other embodiments, the hybrid BoNT has the same subtype for the heavy and light chains, wherein a portion of the heavy or light chain such as the catalytic region is exchanged with a portion from a different subtype. The subtypes can be A1, A2, A3, A4, A5, A6, A7, A8, A9, or A10 (par. [0008]).
The BoNT can be a serotype selected from A, B, C1, D, E, F, or G (par. [0009]).
Johnson et al. reads on the instant application as follows:
Regarding claim 1: the hybrid BoNT comprising a BoNT light chain polypeptide which can be of serotype A (par. [0008-[0009]) is the same as “A recombinant botulinum toxin comprising a recombinant botulinum toxin type A light chain”.
The embodiment of a light chain portion being exchanged with a portion from a different subtype, wherein the subtypes include A1, A2, A3, A4, A5, A6, A7, A8, A9, or A10 (par. [0008]), meets “wherein a sequence of a second domain of first, second, third, and fourth domains of a botulinum toxin type A light chain, other than botulinum toxin type A1, is substituted with a sequence of a second domain of botulinum toxin type Al or a variant thereof”. As set forth above (see Claim Rejections - 35 USC § 112 above), the “first domain”, “second domain”, “third domain”, and “fourth domain” can be any distinct, functional portion of botulinum toxin type A light chain and not limited to a particular amino acid sequence or function.
Regarding claim 2: the light chain portion being replaced with a portion from a different subtype, wherein the subtypes include A1, A2, A3, A4, A5, A6, A7, A8, A9, or A10 (par. [0008]), is the same as “wherein a sequence of the fourth domain of the first, second, third, and fourth domains of the recombinant botulinum toxin type A light chain is further substituted with a sequence of a fourth domain of botulinum toxin type A1 or a variant thereof” in accordance with examiner’s interpretation.
Regarding claims 3-4: applicable subtypes for the BoNT light chain include A2, A3, A4, A5, A6, A7, A8, A9, or A10, which correspond to “wherein the botulinum toxin type A light chain is botulinum toxin type A2, A3, A4, A5, A6, A7 or A8” and “wherein the botulinum toxin type A light chain is botulinum toxin type A4”.
Regarding claim 5: the BoNT heavy chain polypeptide in the hybrid BoNT satisfies “wherein the recombinant botulinum toxin further comprises a botulinum toxin heavy chain”.
Regarding claim 6: the BoNT heavy chain being a serotype selected from A, B, C1, D, E, F, or G (par. [0009]) fulfills “wherein the botulinum toxin type A heavy chain is botulinum toxin type A, B, C, D, E, F, or G”.
Regarding claim 7: the heavy and light chains having the same subtype, wherein the subtype can be A1, A2, A3, A4, A5, A6, A7, A8, A9, or A10 is analogous to “botulinum toxin type A1, A2, A3, A4, A5, A6, A7, or A8”.
Regarding claim 8: suitable subtypes include A1, which is the same as “wherein the botulinum toxin type A heavy chain is botulinum toxin type A1”.
Regarding claim 9: the hybrid BoNT being provided as part of a composition (par. [0013], [0049]) is equivalent to “A composition comprising a recombinant botulinum toxin”.
The hybrid BoNT comprising a heavy chain and a light chain of serotype A (par. [0009] meets the requirement that the recombinant botulinum toxin comprises “the recombinant botulinum toxin type A light chain, and a botulinum toxin heavy chain”.
The composition being formulated as a pharmaceutical composition containing a pharmaceutically acceptable carrier (par. [0013], [0030], [0050]) is akin to “a pharmaceutically acceptable excipient or additive”.
Regarding claim 10: the pharmaceutically acceptable carrier being a standard pharmaceutical carrier like phosphate buffered saline solution (which is a buffer) and including stabilizers and preservatives (par. [0030], [0055]-[0057]) satisfies “wherein the pharmaceutically acceptable excipient or additive is a stabilizer, an ionic compound, a surfactant, a buffer, a lyophilization protectant, or a combination thereof”.
Regarding claim 11: phosphate buffered saline solution comprises sodium chloride (which is a salt) in a buffer solution (par. [0030]), thereby fulfilling “wherein the pharmaceutically acceptable excipient or additive is an amino acid, a salt, a buffer solution, a non-ionic surfactant, a sugar, a sugar alcohol, or a combination thereof”.
Regarding claim 12: the hybrid BoNT being stabilized and preserved with non-protein stabilizers derived non-human and non-animal sources (par. 0058]) is similar to “wherein the composition does not comprise albumin or an animal-derived component”.
Regarding claim 12: the disclosed composition comprising the hybrid BoNT prepared in the form of a liquid, lyophilized formulation, or a unit dose like pre-filled syringe (par. [0050], [0055]-[0058]) is analogous to “in the form of a lyophilized powder, liquid, or prefilled syringe preparation.
Regarding claim 16: the hybrid BoNT-containing composition being formulated as sterile injectable solution suitable for subcutaneous use (par. [0050]) meets “wherein the composition is for transdermal, subcutaneous, or intramuscular administration”.
Regarding claim 21: the prior art teaches that the hybrid BoNT exhibits an altered property including duration of action, neuronal selectivity, and potency compared to BoNTs having the same light and heavy chains of the same subtype (which is the case for wild-type BoNT). For example, the altered property can be greater potency (par. [0009], [0026], [0036]). These teachings satisfy “which has an increased potency or half-life compared to a wild-type botulinum toxin type A”.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 1-13, 16, and 21 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-13, 16, 19, and 21 of co-pending Application No. 18/574838.
The co-pending application is drawn to a recombinant botulinum toxin comprising a recombinant botulinum toxin type A light chain. A sequence of a third domain of first, second, third, and fourth domains of a botulinum toxin type A light chain having a type other than botulinum toxin type A4 is required to be substituted with a sequence of a third domain of botulinum toxin type A4 or a variant thereof.
Although the claims at issue are not identical (the claims of the instant application require a sequence of a botulinum toxin type A light chain’s “second domain” to be substituted instead of “third domain”), they are not patentably distinct from each other because none of the claims define any of the domains. Accordingly, the “first domain”, “second domain”, “third domain”, and “fourth domain” are not limited to a particular amino acid sequence or function of botulinum toxin type A light chain.
Like the claimed invention, the co-pending application’s recombinant botulinum toxin can comprise a botulinum toxin light chain that is of subtype A1, A2, A3, A5, A6, A7 or A8, and further comprise a botulinum toxin heavy chain that is of type A, B, C, D, E, F, or G such as A1. It can also be provided as a composition comprising a pharmaceutically acceptable excipient or additive such as a buffer solution and formulated as a lyophilized powder, liquid, or prefilled syringe preparation suitable for transdermal, subcutaneous, or intramuscular administration.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to MICHELLE F PAGUIO FRISING whose telephone number is (571)272-6224. The examiner can normally be reached Monday-Friday, 8:00 a.m. - 4:00 p.m..
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, Melenie L. Gordon can be reached at (571) 272-8037. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/Michelle F. Paguio Frising/Primary Examiner, Art Unit 1651
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