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
This Office Action is a reply to Applicant’s Amendment and Remarks filed March 3, 2026.
Claim 33 has been canceled. Claims 1, 2, 5, 8, 10, 16-19, 23-26 and 32 have been amended.
Claims 1, 2, 5, 8, 10, 11, 16-19, 23-26, 29, 30 and 32 are pending in the instant application.
This application contains claims 29 and 30 drawn to an invention nonelected without traverse in the replies filed December 31, 2024 and May 22, 2025. A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 CFR 1.144). See MPEP § 821.01.
Accordingly, claims 1, 2, 5, 8, 10, 11, 16-19, 23-26 and 32 have been examined on the merits as detailed below:
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Information Disclosure Statement
Applicant’s information disclosure statement (IDS) filed January 16, 2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Applicant’s IDS filed December 18, 2025 is acknowledged. The submission is in compliance with the provisions of 37 CFR §1.97. Accordingly, the Examiner has considered the information disclosure statement, and a signed copy is enclosed herewith.
Nucleotide Sequence Disclosures
In the previous Office Action mailed December 5, 2025, it was noted that the application failed to comply with the requirements of 37 C.F.R. §1.821-1.825. In view of Applicant’s Amendment to the Specification to provide appropriate sequence identifiers filed March 3, 2026, the present application is fully compliant with the sequence rules and requirements.
Claim Rejections - 35 USC § 112
Claim Rejections - 35 USC § 102
Claim Rejections - 35 USC § 103
Double Patenting
All the previous rejections found in the Office Action mailed December 5, 2025 are moot against claim 33 in view of Applicant’s Amendment filed March 3, 2026 to cancel this claim. Additionally, all the previous rejections found in the Office Action mailed December 5, 2025 are withdrawn against the remaining claims in view of Applicant’s Amendment to the claims filed March 3, 2026; and/or in favor of the new 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph rejection, as failing to comply with the written description requirement as detailed below; and/or in favor of the new nonstatutory obviousness-type double patenting rejections as presented below:
Applicant’s Amendment filed March 3, 2026 necessitated a new ground(s) of rejection as presented below:
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 1, 2, 5, 8, 10, 11, 16-19, 23-26 and 32 are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a written description rejection.
The following quotation from section 2163 of the Manual of Patent Examination Procedure is a brief discussion of what is required in a Specification to satisfy the 35 U.S.C. 112 written description requirement for a generic claim covering several distinct inventions:
The written description requirement for a claimed genus may be satisfied through sufficient description of a representative number of species by actual reduction to practice..., reduction to drawings..., or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus... See Eli Lilly, 119 F.3d at 1568, 43 USPQ2d at 1406.
A "representative number of species" means that the species which are adequately described are representative of the entire genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
Thus, when a claim covers a genus of inventions, the disclosure must provide written support for the entire scope of the genus. Support for a genus is generally found where the Applicant has provided a number of examples sufficient so that one in the art would recognize from the Specification the scope of what is being claimed and that Applicant was in possession of the claimed genus.
The instant claims are drawn to a scaffold suitable for covalently binding at least one endosomal escape enhancer bisdesmosidic triterpene saponin belonging to the type of a 12,13- dehydrooleanane with an aldehyde function in position C-23 to a carrier molecule wherein the carrier molecule comprises or consists of any of a proteinaceous molecule, a protein, a peptide, a nucleic acid, an oligonucleotide, a lipid, a fat, a fatty acid, a nanoparticle, a carbohydrate, the scaffold comprising a polymeric or oligomeric structure and at least one of said bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 covalently bound to said polymeric or oligomeric structure, wherein the scaffold further comprises a first chemical group for covalently coupling of the scaffold to the carrier molecule. NOTE: Applicant is reminded that an oligonucleotide carrier molecule species was elected in their responses filed December 31, 2024 and May 22, 2025. As discussed below, there is insufficient written description for the scaffolds encompassed by the claims.
The instant Specification provides examples wherein a trifunctional linker scaffold was designed and produced with specific chemical end groups dibenzocyclooctyne, trans-cyclooctene or hydrazone bonds for conjugation (labile, (L) conjugation) with on one arm an SO1861 molecule (e.g. saponin) and on the other arm an antisense HSP27BNA oligonucleotide (targeting and inducing degradation of the onco-target hsp27 mRNA in cancer cells) to produce SO1861-L-trifunctional linker-L-HSP27BNA. See the present Specification at FIGs. 16 and 17, for example. SO1861-L-trifunctional linker-L-HSP27BNA was further conjugated with its the third arm (maleimide) to the cysteine residues (Cys) anti-EGFR antibody, cetuximab (cetuximab-Cys-(SO1861-L-trifunctional linker-L-HSP27BNA)4). See Examples 3 and 6, for example. It is noted that other Examples have been provided wherein SO1861 was conjugated to other polymeric structures, however, Applicant is reminded that an oligonucleotide structure was the species elected by Applicant. See Applicant’s elected responses filed December 31, 2024 and May 22, 2025.
The Specification discloses:
For producing cleavable ‘ready to conjugate’ saponins the aldehyde group of SO1861 is reacted with an EMCH (ε-maleimidocaproic acid hydrazide) linker. The hydrazide group of EMCH forms an acid cleavable hydrazone bond with the aldehyde of SO1861.
The art teaches specifically saponins displaying endosomal escape enhancer activity with an aglycone core of the 12,13-dehydrooleanane-type, wherein the core has an aldehyde group at the C-23 position. See WO 2023121446 A1, Table 1. Also, see Table A1 of the present Specification.
There is insufficient written description for the scaffolds encompassed by the claims because there is a substantial variation within the genus of scaffolds and the few species which carry out the functionality of the instant claims (e.g. bisdesmosidic triterpene saponin belonging to the type of a 12,13- dehydrooleanane with an aldehyde function in position C-23 and the ability to induce endosomal escape) does not adequately describe or represent the entire genus of scaffold molecules. As it relates to the oligonucleotide elected species of the present invention, only the saponin, SO1861-EMCH has been reduced to practice.
The written description requirement for claims that require a scaffold comprising bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 and the ability to induce endosomal escape is not met because the claims encompass a genus of scaffolds which are not adequately described.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
To satisfy the written description requirement an applicant must describe the invention is such a way as to convey to one skilled in the art that applicant had the invention in his possession when the application was filed. Ariad Pharms., Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1351 (Fed. Cir. 2010) (en banc). In cases such as the instant application where a genus is claimed, the specification must contain “either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Id. at 1350. However, written description requirement for claims that recite a scaffold comprising bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 and the ability to induce endosomal escape is not met.
The entire genus of scaffold molecule as claimed does not exist in the instant application. That is, adequate written description support does not exist to practice the full scope of the invention claimed. The specification nor the art discloses neither a representative number of species scaffolds nor any structure/function correlation that would enable one of skill to immediately envision the genus of scaffolds required to practice the full scope of the invention. Regarding an oligonucleotide carrier molecule, only a SO1861 molecule has been reduced to practice.
The above position is supported by In University of Rochester v. G.D. Searle & Co., 68 USPQ2d 1424 (W.D.N.Y. 2003). Also, see Enzo Biochem, Inc. v. Gen-Probe Inc., 296 F.3d 1316 (63 U.S.P.Q.2d 1609). The above position is further supported by In re Clarke, 148 USPQ 665, (CCPA 1966), which held that;
“It appears to be well settled that a single species can rarely, if ever, afford support for a generic claim. In re Soll, 25 C.C.P.A. (Patents) 1309, 97 F.2d 623, 38 USPQ 189; In re Wahlforss et al., 28 C.C.P.A. (Patents) 867, 117 F.21 270, 48 USPQ 397. The decisions do not however fix any definite number of species which will establish completion of a generic invention and it seems evident therefrom that such number will vary, depending on the circumstances of particular cases. Thus, in the case of a small genus such as halogens, consisting of four species, a reduction to practice of three, or perhaps even two, might serve to complete the generic invention, while in the case of a genus comprising hundreds of species, a considerably large number of reductions to practice would probably be necessary.”
As stated above, the MPEP states that written description for a genus can be achieved by a representative number of species within a broad generic claim. Given the breadth of the claims, the Specification lacks sufficient variety of species to reflect the variance in the genus.
According to Applicant’s Remarks filed March 3, 2026, claim 1 has been further amended to include, “endosomal escape enhancer bisdesmosidic triterpene saponin…” for defining the saponin according to a functional feature. Applicants further rely on Table A1 to supposedly exemplify that SO1861-EMCH is representative of the claimed endosomal escape enhancer (EEE) saponin because it shares the structural features common to all saponins exhibiting the EEE effect. This is not persuasive because as discussed above, regarding a scaffold comprising bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 and the ability to induce endosomal escape, only SO1861-EMCH is reduced to practice.
In conclusion, the Specification and the prior art as filed does not provide sufficient descriptive support for the myriad of scaffolds embraced by the claims. For the reasons discussed above, the 35 USC § 112 rejection for written description is applicable.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1, 2, 5, 8, 10, 11, 16-19, 23-26 and 32 in the instant application are provisionally rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-2, 5, 7, 11, 13-14, 17 and 23-25 of co-pending US application 17312104; claims 1, 5-6, 9, 12, 13, 20-24, 29-31, 35 and 43 of co-pending US application 17415759; claims 57-59, 61, 64, 65 and 67-78 of co-pending US application 18012754; claims 57-77 of co-pending US application 18012723; claims 57-77 of co-pending US application 18012729; claims 38-50 of co-pending US application 18981715; claims 1, 7-11, 13, 14, 16, 19, 26-30, 32-34, 43, 49 and 50 of co-pending US application 17312193; and claims 87-95 of co-pending US application 17629598. Also, claims 1, 2, 5, 8, 10, 11, 16-19, 23-26 and 32 of the instant application are rejected on the ground of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12453782 B2.
Although the conflicting claims are not identical, they are not patentably distinct from each other because of the following reasons:
The claims of the instant application and co-pending application 17312104 are drawn to overlapping subject matter. Furthermore, the claims of the instant application comprising a scaffold suitable for covalently binding at least one endosomal escape enhancer bisdesmosidic triterpene saponin belonging to the type of a 12,13- dehydrooleanane with an aldehyde function in position C-23 to a carrier molecule wherein the carrier molecule comprises or consists of any of a proteinaceous molecule, a protein, a peptide, a nucleic acid, an oligonucleotide, a lipid, a fat, a fatty acid, a nanoparticle, a carbohydrate, the scaffold comprising a polymeric or oligomeric structure and at least one of said bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 covalently bound to said polymeric or oligomeric structure, wherein the scaffold further comprises a first chemical group for covalently coupling of the scaffold to the carrier molecule embrace and encompass the conjugate of an oligonucleotide and at least one saponin, wherein the oligonucleotide is covalently conjugated to the at least one saponin, wherein the at least one saponin is a bisdesmosidic triterpene saponin belonging to the type of a 12, 13-dehydrooleanane with an aldehyde function in position C-23-and that is covalently bound involving a hydrazone bond to the oligonucleotide via at least one linker of co-pending application 17312104.
The limitations and structural requirements of the instant claims are provided in the supporting disclosure of the co-pending application as certain preferred embodiments. This is provisional obviousness-type double patenting rejection because the conflicting claims have not been patented yet.
The claims of the instant application and co-pending application 17415759 are drawn to overlapping subject matter. Furthermore, the claims of the instant application comprising a scaffold suitable for covalently binding at least one endosomal escape enhancer bisdesmosidic triterpene saponin belonging to the type of a 12,13- dehydrooleanane with an aldehyde function in position C-23 to a carrier molecule wherein the carrier molecule comprises or consists of any of a proteinaceous molecule, a protein, a peptide, a nucleic acid, an oligonucleotide, a lipid, a fat, a fatty acid, a nanoparticle, a carbohydrate, the scaffold comprising a polymeric or oligomeric structure and at least one of said bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 covalently bound to said polymeric or oligomeric structure, wherein the scaffold further comprises a first chemical group for covalently coupling of the scaffold to the carrier molecule embrace and encompass the therapeutic molecule with chemical structure of COMPOUND I of co-pending application 17415759.
The limitations and structural requirements of the instant claims are provided in the supporting disclosure of the co-pending application as certain preferred embodiments. This is provisional obviousness-type double patenting rejection because the conflicting claims have not been patented yet.
The claims of the instant application and co-pending application 18012754 are drawn to overlapping subject matter. Furthermore, the claims of the instant application comprising a scaffold suitable for covalently binding at least one endosomal escape enhancer bisdesmosidic triterpene saponin belonging to the type of a 12,13- dehydrooleanane with an aldehyde function in position C-23 to a carrier molecule wherein the carrier molecule comprises or consists of any of a proteinaceous molecule, a protein, a peptide, a nucleic acid, an oligonucleotide, a lipid, a fat, a fatty acid, a nanoparticle, a carbohydrate, the scaffold comprising a polymeric or oligomeric structure and at least one of said bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 covalently bound to said polymeric or oligomeric structure, wherein the scaffold further comprises a first chemical group for covalently coupling of the scaffold to the carrier molecule embrace and encompass the pharmaceutical combination comprising: a first conjugate comprising an effector molecule and a single-domain antibody (sdAb) for binding to a first cell-surface molecule, wherein the single-domain antibody is a VHH domain that can bind to CD71, wherein the first cell-surface molecule is CD71, wherein the effector molecule and the sdAb are covalently linked to each other and wherein the effector molecule comprises or consists of a nucleic acid or a xeno nucleic acid; a modified saponin, wherein the saponin is a monodesmosidic triterpene glycoside or a bidesmosidic triterpene glycoside, wherein the modified saponin is a monodesmosidic triterpene glycoside or a bidesmosidic triterpene glycoside comprising a modified aglycone core structure being a modified quillaic acid or a modified gypsogenin wherein the aldehyde group in position C-23 of quillaic acid or of gypsogenin, respectively, is chemically modified by transformation into a hydrazone bond; the combination optionally further comprising a pharmaceutically acceptable excipient and/or pharmaceutically acceptable diluent of co-pending application 18012754.
The limitations and structural requirements of the instant claims are provided in the supporting disclosure of the co-pending application as certain preferred embodiments. This is provisional obviousness-type double patenting rejection because the conflicting claims have not been patented yet.
The claims of the instant application and co-pending application 18012723 are drawn to overlapping subject matter. Furthermore, the claims of the instant application comprising a scaffold suitable for covalently binding at least one endosomal escape enhancer bisdesmosidic triterpene saponin belonging to the type of a 12,13- dehydrooleanane with an aldehyde function in position C-23 to a carrier molecule wherein the carrier molecule comprises or consists of any of a proteinaceous molecule, a protein, a peptide, a nucleic acid, an oligonucleotide, a lipid, a fat, a fatty acid, a nanoparticle, a carbohydrate, the scaffold comprising a polymeric or oligomeric structure and at least one of said bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 covalently bound to said polymeric or oligomeric structure, wherein the scaffold further comprises a first chemical group for covalently coupling of the scaffold to the carrier molecule embrace and encompass the conjugate for transferring an effector molecule from outside a cell into said cell, the conjugate comprising:- an effector molecule comprising or consisting of an oligonucleotide; - at least one single-domain antibody capable of binding to a binding site on a cell- surface molecule of said cell (sdAb), and - at least one saponin, wherein: the effector molecule, the sdAb, and the saponin are covalently bound to each other, wherein the covalent binding of the saponin is made via a linker, and the saponin is a mono-desmosidic triterpene glycoside or is a bi-desmosidic triterpene glycoside of co-pending application 18012723.
The limitations and structural requirements of the instant claims are provided in the supporting disclosure of the co-pending application as certain preferred embodiments. This is provisional obviousness-type double patenting rejection because the conflicting claims have not been patented yet.
The claims of the instant application and co-pending application 18012729 are drawn to overlapping subject matter. Furthermore, the claims of the instant application comprising a scaffold suitable for covalently binding at least one endosomal escape enhancer bisdesmosidic triterpene saponin belonging to the type of a 12,13- dehydrooleanane with an aldehyde function in position C-23 to a carrier molecule wherein the carrier molecule comprises or consists of any of a proteinaceous molecule, a protein, a peptide, a nucleic acid, an oligonucleotide, a lipid, a fat, a fatty acid, a nanoparticle, a carbohydrate, the scaffold comprising a polymeric or oligomeric structure and at least one of said bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 covalently bound to said polymeric or oligomeric structure, wherein the scaffold further comprises a first chemical group for covalently coupling of the scaffold to the carrier molecule embrace and encompass the conjugate for transferring an effector molecule from outside a cell into said cell, the conjugate comprising:- an effector molecule, wherein the effector molecule is a pharmaceutically active substance; - at least one single-domain antibody (sdAb); and - at least one endosomal escape enhancer saponin; wherein: the effector molecule, the sdAb, and the saponin are covalently bound to each other, directly or via at least one linker; the at least one saponin is a mono-desmosidic triterpene glycoside or is a bi- desmosidic triterpene glycoside; and the sdAb is capable of binding to a binding site on the cell-surface molecule of said cell and inducing endocytosis of the conjugate, and wherein the effector molecule comprises or consists of a nucleic acid of co-pending application 18012729.
The limitations and structural requirements of the instant claims are provided in the supporting disclosure of the co-pending application as certain preferred embodiments. This is provisional obviousness-type double patenting rejection because the conflicting claims have not been patented yet.
The claims of the instant application and co-pending application 18981715 are drawn to overlapping subject matter. Furthermore, the claims of the instant application comprising a scaffold suitable for covalently binding at least one endosomal escape enhancer bisdesmosidic triterpene saponin belonging to the type of a 12,13- dehydrooleanane with an aldehyde function in position C-23 to a carrier molecule wherein the carrier molecule comprises or consists of any of a proteinaceous molecule, a protein, a peptide, a nucleic acid, an oligonucleotide, a lipid, a fat, a fatty acid, a nanoparticle, a carbohydrate, the scaffold comprising a polymeric or oligomeric structure and at least one of said bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 covalently bound to said polymeric or oligomeric structure, wherein the scaffold further comprises a first chemical group for covalently coupling of the scaffold to the carrier molecule embrace and encompass the conjugate comprising a first proteinaceous molecule comprising a binding site for binding to an epitope on a cell-surface molecule and at least one saponin covalently bound to said first proteinaceous molecule and comprising at least one effector moiety, of Structure C, wherein “E” of Structure C is any one or more of an oligonucleotide of co-pending application 18981715.
The limitations and structural requirements of the instant claims are provided in the supporting disclosure of the co-pending application as certain preferred embodiments. This is provisional obviousness-type double patenting rejection because the conflicting claims have not been patented yet.
The claims of the instant application and co-pending application 17312193 are drawn to overlapping subject matter. Furthermore, the claims of the instant application comprising a scaffold suitable for covalently binding at least one endosomal escape enhancer bisdesmosidic triterpene saponin belonging to the type of a 12,13- dehydrooleanane with an aldehyde function in position C-23 to a carrier molecule wherein the carrier molecule comprises or consists of any of a proteinaceous molecule, a protein, a peptide, a nucleic acid, an oligonucleotide, a lipid, a fat, a fatty acid, a nanoparticle, a carbohydrate, the scaffold comprising a polymeric or oligomeric structure and at least one of said bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 covalently bound to said polymeric or oligomeric structure, wherein the scaffold further comprises a first chemical group for covalently coupling of the scaffold to the carrier molecule embrace and encompass the first proteinaceous molecule comprising a first binding site for binding to a first epitope of a first cell-surface molecule, the first proteinaceous molecule provided with at least one saponin covalently bound via at least one linker and/or via an oligomeric or polymeric scaffold to an amino-acid residue of said first proteinaceous molecule or via at least one linker and an oligomeric or polymeric scaffold to an amino-acid residue of said first proteinaceous molecule, or covalently bound directly to an amino-acid residue of said first proteinaceous molecule, wherein the first binding site comprises an immunoglobulin, or at least one binding domain of an immunoglobulin and/or at least one binding fragment of an immunoglobulin or at least one binding domain of an immunoglobulin and at least one binding fragment of an immunoelobulin an antibody; wherein the at least one saponin is a triterpenoid saponin or a bisdesmosidic triterpene saponin belonging to the type of a 12, 13 dehydrooleanane with an aldehyde function in position C-23 of co-pending application 17312193.
The limitations and structural requirements of the instant claims are provided in the supporting disclosure of the co-pending application as certain preferred embodiments. This is provisional obviousness-type double patenting rejection because the conflicting claims have not been patented yet.
The claims of the instant application and co-pending application 17629598 are drawn to overlapping subject matter. Furthermore, the claims of the instant application comprising a scaffold suitable for covalently binding at least one endosomal escape enhancer bisdesmosidic triterpene saponin belonging to the type of a 12,13- dehydrooleanane with an aldehyde function in position C-23 to a carrier molecule wherein the carrier molecule comprises or consists of any of a proteinaceous molecule, a protein, a peptide, a nucleic acid, an oligonucleotide, a lipid, a fat, a fatty acid, a nanoparticle, a carbohydrate, the scaffold comprising a polymeric or oligomeric structure and at least one of said bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 covalently bound to said polymeric or oligomeric structure, wherein the scaffold further comprises a first chemical group for covalently coupling of the scaffold to the carrier molecule embrace and encompass the functionalized glycoside moiety having endosomal and/or lysosomal escape enhancing activity and having a molecular structure comprising at least one S moiety and at least one connector moiety L*, with general structure (0) of co-pending application 17629598.
The limitations and structural requirements of the instant claims are provided in the supporting disclosure of the co-pending application as certain preferred embodiments. This is provisional obviousness-type double patenting rejection because the conflicting claims have not been patented yet.
Claims 1, 2, 5, 8, 10, 11, 16-19, 23-26 and 32 are rejected on the grounds of nonstatutory obviousness-type double patenting as being unpatentable over claims 1-17 of U.S. Patent No. 12453782 B2. An obviousness-type double patenting rejection is appropriate where the conflicting claims are not identical, but an examined application claim not is patentably distinct from the reference claim(s) because the examined 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).
Although the conflicting claims are not identical, they are not patentably distinct from each other because the scaffold suitable for covalently binding at least one endosomal escape enhancer bisdesmosidic triterpene saponin belonging to the type of a 12,13- dehydrooleanane with an aldehyde function in position C-23 to a carrier molecule wherein the carrier molecule comprises or consists of any of a proteinaceous molecule, a protein, a peptide, a nucleic acid, an oligonucleotide, a lipid, a fat, a fatty acid, a nanoparticle, a carbohydrate, the scaffold comprising a polymeric or oligomeric structure and at least one of said bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 covalently bound to said polymeric or oligomeric structure, wherein the scaffold further comprises a first chemical group for covalently coupling of the scaffold to the carrier molecule encompasses the conjugate comprising a cell-surface molecule targeting molecule and at least one effector moiety and further comprising at least one covalently bound saponin, wherein the at least one saponin is a triterpenoid saponin and/or a bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 and comprising a glucuronic acid function in a carbohydrate substituent at the C-3beta-OH group of the saponin, and wherein the cell-surface molecule targeting molecule comprises or consists of an immunoglobulin, at least one binding domain of an immunoglobulin and/or at least one binding fragment of an immunoglobulin, an antibody, an IgG, a molecule comprising or consisting of a Vhh domain or Vh domain, a Fab, an scFv, an Fv, a dAb, an F(ab)2, Fcab fragment, which can bind to the cell-surface molecule, and wherein the at least one effector moiety comprises or consists of any one or more of oligonucleotide, a nucleic acid and a xeno nucleic acid, or selected from any one or more of a vector, a gene, a cell suicide inducing transgene, deoxyribonucleic acid (DNA), ribonucleic acid (RNA), anti-sense oligonucleotide (ASO, AON), short interfering RNA (siRNA), microRNA (miRNA), DNA aptamer, RNA aptamer, mRNA, mini-circle DNA, peptide nucleic acid (PNA), phosphoramidate morpholino oligomer (PMO), locked nucleic acid (LNA), bridged nucleic acid (BNA), 2′-deoxy-2′-fluoroarabino nucleic acid (FANA), 2′-O-methoxyethyl-RNA (MOE), 2′-O,4′-aminoethylene bridged nucleic acid, 3′-fluoro hexitol nucleic acid (FHNA), a plasmid, glycol nucleic acid (GNA) and threose nucleic acid (TNA) of U.S. Patent No. 12453782.
The claims of U.S. Patent No. 12453782 overlaps in scope and fully embraces that which is claimed in the present invention. Furthermore, the limitations and structural requirements of the instant claims are provided in the supporting disclosure of the issued Patent as certain preferred embodiments.
A terminal disclaimer disclaiming the terminal portion of any patent granted on this application which would extend beyond the expiration date of U.S. Patent No. 12453782 is required, or some other appropriate action.
Response to Arguments
In response to the provisional rejections, Applicants may want to argue that the cancellation of claim 33 overcomes the rejections as the instant claims no longer embrace a scaffold comprising a carrier molecule and an oligonucleotide that could overlap with claims of the provisional applications. This anticipated argument would not be persuasive since, as explained above, the scaffold suitable for covalently binding at least one endosomal escape enhancer bisdesmosidic triterpene saponin belonging to the type of a 12,13- dehydrooleanane with an aldehyde function in position C-23 to a carrier molecule wherein the carrier molecule comprises or consists of any of a proteinaceous molecule, a protein, a peptide, a nucleic acid, an oligonucleotide, a lipid, a fat, a fatty acid, a nanoparticle, a carbohydrate, the scaffold comprising a polymeric or oligomeric structure and at least one of said bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 covalently bound to said polymeric or oligomeric structure, wherein the scaffold further comprises a first chemical group for covalently coupling of the scaffold to the carrier molecule of the instant invention encompasses the conjugate; therapeutic compound; proteinaceous molecule; or functionalized glycoside moiety of the provisional applications. Applicant is reminded that the limitations and structural requirements of the instant claims are provided in the supporting disclosure of the co-pending applications as certain preferred embodiments.
Markush Rejection
Claims 1, 2, 5, 8, 10, 11, 16-19, 23-26 and 32 are rejected on the judicially-created basis that it contains an improper Markush grouping of alternatives. See In re Harnisch, 631 F.2d 716, 721-22 (CCPA 1980) and Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). The improper Markush grouping includes species of the claimed invention that do not share both a substantial structural feature and a common use that flows from the substantial structural feature. The members of the improper Markush grouping do not share a substantial feature and/or a common use that flows from the substantial structural feature for the following reasons: The claims are directed to a multitude of scaffolds suitable for covalently binding at least one endosomal escape enhancer bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 molecule to a carrier molecule with no common searchable core. The scaffolds have no common structure as the carrier molecules comprise different and unique polymeric or oligomeric structures (e.g. proteins, peptides, nucleic acids, lipid, fats, carbohydrates, etc.).
The Markush groupings of carrier molecules are improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use.
In response to this rejection, Applicant should either amend the claim(s) to recite only individual species or grouping of species that share a substantial structural feature as well as a common use that flows from the substantial structural feature, or present a sufficient showing that the species recited in the alternative of the claims(s) in fact share a substantial structural feature as well as a common use that flows from the substantial structural feature. This is a rejection on the merits and may be appealed to the Board of Patent Appeals and Interferences in accordance with 35 U.S.C. 134 and 37 CFR 41.31(a)(1).
When the Markush grouping is for alternatives of chemical compounds, they shall be regarded as being of a similar nature where the following criteria are fulfilled:
(A) All alternatives have a common property or activity; and
(B) (1) A common structure is present, i.e., a significant structural element is shared by all of the alternatives; or
(B) (2) In cases where the common structure cannot be the unifying criteria, all alternatives belong to a recognized class of chemical compounds in the art to which the invention pertains.
In paragraph (B)(1), above, the words “significant structural element is shared by all of the alternatives” refer to cases where the compounds share a common chemical structure which occupies a large portion of their structures, or in case the compounds have in common only a small portion of their structures, the commonly shared structure constitutes a structurally distinctive portion in view of existing prior art, and the common structure is essential to the common property or activity. The structural element may be a single component or a combination of individual components linked together.
In paragraph (B)(2), above, the words “recognized class of chemical compounds” mean that there is an expectation from the knowledge in the art that members of the class will behave in the same way in the context of the claimed invention. In other words, each member could be substituted one for the other, with the expectation that the same intended result would be achieved.
In order for the members of the Markush group to belong to “recognized class of chemical compounds” there must be an expectation that the members of the class will behave in the same way in the context of the claimed invention. In other words, each member of the class could be substituted one for the other with the expectation that the same intended result would be achieved. In the instant case, the scaffolds suitable for covalently binding at least one endosomal escape enhancer bisdesmosidic triterpene saponin belonging to the type of a 12,13-dehydrooleanane with an aldehyde function in position C-23 molecule to a carrier molecule have no common searchable core. There is no expectation that any one of the carrier molecules as claimed can be substituted with each other and have the expectation of the same activity.
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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Terra C. Gibbs whose telephone number is 571-272-0758. The examiner can normally be reached from 8 am - 5 pm M-F.
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/TERRA C GIBBS/ Primary Examiner, Art Unit 1635
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