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
Response to Election/Restriction filed on May 26, 2026 is acknowledged. Claims 1-19 are pending in the instant application.
Election/Restrictions
Applicant elected without traverse Group I (claims 1-15) drawn to a method of conjugation and without traverse Formula III (claim 6), riboflavin tetrabutyrate (claim 7), TRAP-6 as the peptide and SEQ ID NO:12 as the second reactant in the reply filed May 26, 2026. After further review, the election of species is withdrawn.
The restriction is deemed proper and is made FINAL in this office action. Claims 16-19 are withdrawn from consideration as being drawn to a non-elected invention/species.
Claims 1-15 are examined on the merits of this office action.
Claim Objections
Claim 5 is objected to for the following informality: the limitation of “consisting an” should be replaced with -consisting of an-.
Claim 9 is objected to for the following informality: the acronyms of “DMF” AND “DMSO” should be spelled out in their first instance.
Claim Rejections - 35 USC § 112, First Paragraph
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 1-6, 8-15 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
MPEP § 2163 states that 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, 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.
Scope of the claims
Claim 1 recites in part “…a first catalyst configured to decarboxylate the C-terminal end of the peptide in the presence of the first radiation”. The claims does not limit the first catalyst by any structural, chemical or compositional characteristics. Instead, the catalyst is defined solely by its functional capability of decarboxylating the peptide under irradiation. Consequently, the claim encompasses a broad genus of catalysts capable of performing the recited function, regardless of catalyst class, molecular structure or chemical identity.
Therefore, to meet the written description requirement of 35 U.S.C. § 112, first paragraph, the specification must disclose a representative number of species that meet both the structural and functional limitations of the genus or the specification and/or the prior art must identify the structural elements that correlate to the claimed function in a manner that demonstrates to one of ordinary skill in the art that Applicant was in possession of the claimed genus at the time the application was filed.
Actual Reduction to Practice
MPEP § 2163 states that 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. 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.
The specification provides experimental examples utilizing riboflavin tetrabutyrate as the photocatalyst and demonstrates successful preparation of peptide conjugates using the catalyst. The specification additionally identifies several other photocatalysts, including lumiflavin, riboflavin derivatives, iridium photocatalysts, and mesityl acridinium catalysts. Accordingly, the specification demonstrates possession of certain exemplary catalyst species and catalyst families. However, reduction to practice of several exemplary species does not, by itself, establish possession of the entire functionally defined catalyst genus encompassed by claim 1.
Accordingly, the disclosed examples do not constitute representative species of the claimed genus. Therefore, the instant specification has failed to meet the written description requirement by actual reduction to practice of a representative number of species alone.
Sufficient relevant identifying characteristic
MPEP § 2163 states that 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, 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 thereof.
The specification identifies several specific catalyst species and catalyst classes but does not disclose structural characteristics common to the entire claimed genus. In particular, the specification does not describe common molecular features, catalyst architecture, ligand characteristics, properties, or other structural characteristics that distinguish catalysts capable of performing the claimed decarboxylation reaction from catalysts that cannot perform the claimed function. Rather, the specification principally identifies catalysts by the result they achieve.
Physical/Chemical Properties
The specification does not identify common physical or chemical properties shared by substantially all catalysts encompassed by claim 1. For example, the specification does not describe ranges of oxidation potential, excited state reduction potential, absorption characteristics or other physicochemical parameters that correlate with successful peptide decarboxylation under the claimed reaction conditions. Accordingly, the disclosure does not provide objective identifying characteristics permitting one of ordinary skill in the art to recognize the full scope of catalysts encompassed by the claims.
Functional characteristics when coupled with a known or disclosed correlation between function and structure:
Claim 1 defines the first catalyst exclusively by the functional limitation that is “configured to decarboxylate the C-terminal end of the peptide in the presence of the first radiation”. While functional language may satisfy the written description requirement when accompanied by either representative species or a known or disclosed correlation between structure and function, the specification does not identify structural features common to catalysts capable of performing the claimed function, nor does it explain the structural basis by which one of ordinary could determine whether a catalyst falls within the claimed genus. The specification lists several unrelated catalyst families but does not disclose a structural or physicochemical correlation that defines the full breadth of catalyst capable of performing the claimed decarboxylation. Thus, the disclosure defines the claimed catalyst primarily by its desired function rather than structure or other characteristic sufficient to demonstrate possession.
Method of Making
The specification identifies commercially available catalyst examples and provides reaction conditions for carrying out the disclosed process using those examples. However, the specification does not describe how additional catalysts encompassed by the broad functional limitation would be selected, designed, or identified. Furthermore, the specification does not provide criteria by which one of ordinary skill in the art could determine whether undisclosed catalyst structures fall within the claimed genus.
Conclusion
Although the specification demonstrates possession of several exemplary photocatalyst species and catalyst families, claim 1 encompasses a broader genus of catalysts defined solely by the functional limitation that the catalyst is capable of decarboxylating the peptide under radiation. The specification does not disclose structural characteristics common to the claimed genus, properties that identify members of the genus or a sufficient correlation between structure and function to reasonably convey possession of the full scope of the claimed genus. Thus, the specification does not reasonably convey to one of ordinary skill in the art that the inventors were in possession of the full breadth of the claimed genus.
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.
Claims 13-14 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 13 claims “The method according to claim 1, wherein the peptide comprises a c-terminal residue selected from the group comprising alanine….”
MPEP 2173.05 (h) states “A Markush grouping is a closed group of alternatives, i.e., the selection is made from a group "consisting of" (rather than "comprising" or "including") the alternative members. Abbott Labs., 334 F.3d at 1280, 67 USPQ2d at 1196. If a Markush grouping requires a material selected from an open list of alternatives (e.g., selected from the group "comprising" or "consisting essentially of" the recited alternatives), the claim should generally be rejected under 35 U.S.C. 112(b) as indefinite because it is unclear what other alternatives are intended to be encompassed by the claim. See In re Kiely, 2022 USPQ2d 532 at 2* (Fed. Cir. 2022) (each independent claim recites "a selection from the group comprising a person, an animal, an animated character, a creature, an alien, a toy, a structure, a vegetable, and a fruit." … (emphasis added). "Given the breadth of variation among the specified alternatives and the use of the open-ended word ’comprising’ to define the scope of the list, we affirm the Board's conclusion that the pending claims recite improper Markush language and are indefinite under § 112(b)."). If a claim is intended to encompass combinations or mixtures of the alternatives set forth in the Markush grouping, the claim may include qualifying language preceding the recited alternatives (such as "at least one member" selected from the group), or within the list of alternatives (such as "or mixtures thereof"). Id. at 1281. See also MPEP § 2111.03.
Claim 14 recites that “the cargo comprises a second peptide, wherein the second peptide has an N-terminal cysteine residue”. However, claim 14 does not identify a corresponding first peptide or define Formula II as comprising a first peptide. Thus, it is unclear to what the recite “second peptide” refers, and the scope of claim 14 cannot be determined with reasonable certainty.
Claim Rejections - 35 USC § 103
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.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 1-5, 7-11, 13-15 are rejected under 35 U.S.C. 103 as being unpatentable over Bloom (NATURE CHEMISTRY, VOL 10, FEBRUARY 2018, pages 205-211) in view of Ollivier (Organic Letters, 2010, Volume 12, No. 22, pages 5238-5241) and Liu (Synthesis 2019, 51, 2759–2791)
Bloom teaches a method of modifying peptides and protein by visible light photo redox catalysis. Specifically, Bloom teaches a first stage comprising reacting a peptide having a c-terminal carboxylic acid with an electron deficient alpha, Beta unsaturated Michael acceptor in the presence of a flavin photocatalysis and visible light (radiation), whereby the photocatalyst is configured to oxidatively decarboxylate the C-terminal carboxylate to generate an alpha amino radical that undergoes radical conjugate (Michael) addition to the electron deficient alkene to result in a peptide-Michael acceptor conjugate (see Figure 2a and discussion thereof). Regarding claims 1 and 7, Bloom further teaches riboflavin tetrabutyrate and lumiflavin as suitable photocatalysts (see Table 1) and demonstrates successful modification of peptide and protein substrates using these methods (see Figures 3-4). Bloom teaches a first stage comprising reacting the C-terminal end of a peptide with a first reactant in the presence of a first catalyst and visible light, wherein the catalyst is configured to decarboxylate the C-terminal end of the peptide upon irradiation to generate an alpha amino radical. Bloom teaches that the Michael acceptor may be modified to incorporate additional biorthogonal handles, including demonstrated alkynes and proposed biotin and azide bearing derivatives to facilitate subsequent bioconjugation (see page 209, right hand column into page 210). Bloom teaches that modifying the Michael acceptor to incorporate additional bioorthagonal handles for subsequent bioconjugation, demonstrating that the Michael acceptor serves as a vehicle for delivering functional groups to the peptide during photoredox mediated conjugation.
Bloom is silent to a Michael acceptor incorporating the claimed SEA functionality or the subsequent reaction of the resulting intermediate with a second reactant comprising a cargo through SEA ligation.
Ollivier teaches peptides incorporating the bis (2-sulfanylethyl)amino (SEA functionality, including the oxidized cyclic disulfide form, and teaches that the SEA group functions as a latent peptide ligation handle useful for chemoselective native peptide ligation (see Abstract, page 5238, Scheme 1, page 5239). Ollivier further teaches preparation of SEA containing peptide building blocks suitable for incorporation into peptides (Scheme 2, page 5239; Scheme 3, page 5240). Ollivier additionally teaches that SEA containing peptides react with N-terminal cysteine containing peptide coupling partners to form native peptide bonds, thereby conjugating an additional peptide fragment to the SEA containing intermediate. Thus, Ollivier teaches a second stage in which SEA containing intermediate is reacted with a second reactant comprising a cysteine containing coupling partner wherein the cysteine containing coupling partner constitutes the claimed second reactant and the attached peptide fragment constitutes the claimed cargo. Ollivier concludes that SEA ligation is a chemoselective, regioselective, and racemization free peptide ligation method that enriches the peptide ligation toolbox and has broad utility in chemical and biochemical applications (see Conclusion, page 5241).
Liu reviews visible light photoredox peptide functionalization and conforms that photoredox mediated decarboxylative conjugate addition had become and established and predictable strategy for peptide modification. Liu teaches oxidation of peptide C-terminal carboxylates to alpha-amino radicals followed by conjugate additional to electron deficient Michael acceptors using flavin photocatalysts, including riboflavin tetrabutyrate (Scheme 36, pp. 2779-2780), and further teaches peptide functionalization through radical Michael addition chemistry (Scheme 37). Liu evidences that photoredox mediated peptide functionalization through Michael acceptor chemistry was an established and predicable platform, thereby supporting a reasonable expectation of success.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to modify the electron deficient Michael acceptor employed by MacMillan to incorporate the known bis(2-sulfanylethyl)amino (SEA) functionality taught by Ollivier. MacMillan teaches that electron deficient alpha,beta unsaturated Michael acceptors are useful reaction partners for peptide derived alpha amino radicals generated by photoredox decarboxylation to introduce functionality at the peptide C-terminus. Ollivier teaches that the SEA functionality is a well-established latent peptide ligation handle that enables subsequent chemoselective native peptide ligation with cysteine containing coupling partners to attach an additional component, such as a peptide cargo, and teaches that incorporation of the SEA expands the peptide ligation toolbox and is useful in chemical and biochemical applications (Abstract, page 5238, conclusion, page 5241). One of ordinary skill in the art would have recognized that Bloom teaches modifying the Michael acceptor to incorporate additional biorthogonal handles for subsequent bioconjugation. Accordingly, it would have been obvious to incorporate the known SEA ligation handle into Blooms modified Michael acceptor, whereby the Michael acceptor retains its electron deficient functionality during the photoreceptor conjugate addition reaction and transfers the attached SEA ligation handle to the peptide. Such modification would have been expected to provide peptides bearing a useful downstream ligation handle, thereby enabling the resulting SEA containing intermediate to undergo the SEA ligation reaction taught buy Ollivier with a cysteine containing second reactant constituting the claimed second reactant to attach a desired peptide cargo. Liu further confirms that photoredox peptide functionalization through Michael acceptor chemistry was an established and predictable platform, thereby providing a reasonable expectation of success of the combined methods.
Furthermore, because Bloom teaches that the Michael acceptor may be modified to incorporate additional biorthogonal handles for subsequent bioconjugation, and Ollivier teaches that the SEA moiety is well established orthogonal peptide ligation handle, a person of ordinary skill in the art would have been motivated to incorporate the known SEA ligation handle in Blooms modified Michale acceptor, thereby producing a bifunctional reagent that retains the Michael acceptor functionality during photoredox mediated peptide modification while transferring SEA ligation handle to the peptide, thereby enabling subsequent attachment of a peptide cargo through established SEA ligation chemistry.
Regarding formula I of claim 1, the combination of Bloom in view of Liu and Ollivier teach the structure of formula I. Regarding formula II, Ollivier teaches reacting a SEA containing intermediate with an N-terminal cysteine containing peptide coupling partner (cargo) corresponding to the claimed second reactant of Formula II.
Regarding claim 2, Ollivier teaches the claimed SEA corresponding to n1 and n2 equal to 1.
Regarding claims 3-4, selection of hydrogen and lower alkyl substituents on the Michael acceptor represents routine optimization of known alpha, Beta-unsaturated Michale acceptors taught by Bloom. Nevertheless, Bloom teaches electron deficient Michael acceptors including diethyl ethylidenemalonate (see Figure 3).
Regarding claim 5, Bloom expressly teaches electron deficient Michael acceptors. Selection of convention electron withdrawn groups, such as an ester, cyano or trifluoromethyl, would have been an obvious matter of routine optimization. Nevertheless, Bloom teaches electron deficient Michael acceptors including diethyl ethylidenemalonate (see Figure 3).
Regarding claim 8, Bloom teaches irradiation with visible blue light (34 W Blue LED), which falls within the claimed wavelength range of 375-525 nm (see Experimental conditions, Figure 4, caption, Table 1).
Regarding claim 9, Bloom teaches conducting the reaction in aqueous buffer and 95:5 buffer:glycerol solvent systems (see Supplementary Table 2, general procediures, supplementary page 7), wherein the peptide is dissolved in water. These teachings render the claimed solvent system comprising water obvious.
Regarding claim 10, Bloom teaches degassing the reaction mixture by sparging with nitrogen for 10-15 minutes before irradiation (see General procedure, supplementary page 7). It would have been obvious to one of ordinary skill in the art to optimize the residual dissolved oxygen concentration, including concentrations of less than equal to 1 ppm, as a matter of routine optimization to minimize oxygen quenching of the photoredox catalyst and improve reaction efficiency.
Regarding claim 11, Bloom teaches isolating the reaction product by removing solvent under reduced pressure following HPLC analysis and purification of the modified peptide products (see General procedure, supplementary pages 7-8), thereby teaching separation of the reaction intermediate from unreacted materials.
Regarding claim 13, Bloom teaches peptide substrates having a C-terminal proline residue, for example the tetrapeptide substrates with a c-terminal proline (see figures 3-4, supplementary tables 1-2. Since proline is one of the recited C-terminal residues, Bloom teaches the claim limitation.
Regarding claim 14, Ollivier teaches ligation of an SEA-functionalized peptide with a second peptide comprising an N-terminal cysteine residue to form a peptide conjugate (e.g. scheme 1 and corresponding description). Accordingly, Ollivier teaches the claimed cargo comprising a second peptide having an N-terminal cysteine residue.
Regarding claim 15, Bloom teaches that the disclosed photoredox bioconjugation strategy is applicable to antibodies, noting that the development of reliable site selective methods is driven by the need for antibody drug conjugates and further teaching application of the disclosed methodology to the selective functionalization of proteins, enzymes, and antibodies with biologically active conjugates (introduction, conclusion paragraph). It would have been obvious to one of ordinary skill in the art to employ an antibody as the claimed cargo.
Claim(s) 12 is rejected under 35 U.S.C. 103 as being unpatentable over Bloom (NATURE CHEMISTRY, VOL 10, FEBRUARY 2018, pages 205-211) in view of Ollivier (Organic Letters, 2010, Volume 12, No. 22, pages 5238-5241) and Liu (Synthesis 2019, 51, 2759–2791) as applied to claims 1-5, 7-11, 13-15 above in further view of Raibaut (Org. Lett., Vol. 15, No. 21, 2013, pages 5516-5519 and supplement thereof).
The teachings of Bloom in view of Ollivier and Liu are provided in the above rejection.
Regarding claim 12, Ollivier teaches that SEA functionalized peptides undergo ligation with peptides comprising an N-terminal cysteine residue to form peptide conjugates but is silent to the conjugation being formed in a degassed buffer under inert gas. Raibaut teaches performing SEA mediated native chemical ligation under a nitrogen atmosphere (Supporting information, page S6, section 4, Kinetically controlled ligation), thereby evidencing conventional reaction conditions for minimizing oxidation during SEA ligation. One of ordinary skill in the art would have been motivated to perform the second stage SEA ligation in a degassed buffer under inert gas to minimize oxidation of sulfur containing SEA intermediates and N-terminal cysteine residues, thereby maintaining reactive thiol species and predictably improving ligation efficiency.
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 1-15 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of copending Application No.18/282288 (reference application) in view of Bloom (NATURE CHEMISTRY, VOL 10, FEBRUARY 2018, pages 205-211) in view of Ollivier (Organic Letters, 2010, Volume 12, No. 22, pages 5238-5241) and Raibaut (Org. Lett., Vol. 15, No. 21, 2013, pages 5516-5519 and supplement thereof). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant application claims a method for providing a cargo to a C-terminal end of a peptide, the method comprising a first stage and a second stage, wherein the first stage comprises reacting the C-terminal end of the peptide with a first reactant in the presence of a first catalyst and first radiation to provide a first intermediate, wherein the first catalyst is configured to decarboxylate the C-terminal end of the peptide in the presence of the first radiation, and wherein the first reactant has a first chemical structure according to formula I:
PNG
media_image1.png
311
672
media_image1.png
Greyscale
wherein R and R′are each independently selected from the group consisting of H, and alkyl groups;
wherein R″ is an electron withdrawing group comprising a functional group selected from the group consisting of an ester, a thioester, an amide, a ketone, a nitro, a sulfoxide, a sulfone, a phosphate ester, an acylhydrazide, a cyano group, and a trihalogenmethyl group;
wherein n1 and n2 are each independently selected from the range of 1-2;
and wherein the second stage comprises exposing the first intermediate to a second reactant, wherein the second reactant has a second chemical structure according to formula II:
PNG
media_image2.png
255
617
media_image2.png
Greyscale
wherein X is O or NH, and wherein R1 comprises the cargo” (see claim 1). The instant application further claims “wherein n1=1, and wherein n2=1” (see claim 2); wherein R and R′ are selected from the group consisting of H and alkyl groups comprising 1-6 C atoms (claim 3); wherein one or more of R and R′ are H (claim 4); wherein the first reactant has a first chemical structure according to structure III:
PNG
media_image3.png
258
700
media_image3.png
Greyscale
(Claim 6); wherein the first catalyst comprises riboflavin tetrabutyrate (claim 7); wherein the first radiation is selected from the range of 375-525 nm (claim 8); wherein the first stage is executed in a first mixture comprising a first solvent, wherein the first solvent comprises one or more of DMF, DMSO, and water (claim 9); wherein the first mixture comprises ≤1 ppm dissolved oxygen (claim 10); wherein the second stage is performed in a degassed buffer under inert gas (claim 12); wherein the peptide comprises a C-terminal residue selected from the group comprising alanine, arginine, asparagine, aspartate, cysteine, glutamate, glutamine, histidine, isoleucine, leucine, lysine, methionine, phenylalanine, proline, pyrrolysine, selenocysteine, serine, threonine, tryptophan, tyrosine, and valine (claim 13); wherein the cargo comprises a second peptide, wherein the second peptide has an N-terminal cysteine residue (claim 14); wherein the cargo comprises an antibody (claim 15).
Co-pending 18/282288 the instant application claims a method for providing a cargo to a C-terminal end of a peptide, the method comprising a first stage and a second stage, wherein the first stage comprises reacting the C-terminal end of the peptide with a first reactant in the presence of a first catalyst and first radiation to provide a first intermediate, wherein the first catalyst is configured to decarboxylate the C-terminal end of the peptide in the presence of the first radiation, and wherein the first reactant has a first chemical structure according to formula I:
formula I:
PNG
media_image4.png
189
574
media_image4.png
Greyscale
wherein R0 is selected from the group consisting of H, halides, O-acyl groups, carbonate groups, sulfonate groups, and NR3 groups, wherein each R is independently selected from H and alkyl groups, or wherein NR3 comprises pyridinium or a derivative thereof;
wherein R′ is selected from the group consisting of H, aryl groups and alkyl groups;
wherein R″ is an electron withdrawing group comprising a functional group selected from the group consisting of an ester, a thioester, an amide, a ketone, a nitro, a sulfoxide, a sulfone, a phosphate ester, an acylhydrazide, a cyano group, and a trihalogenmethyl group;
and wherein the second stage comprises exposing the first intermediate to a second reactant, wherein the second reactant has a second chemical structure according to formula III:
PNG
media_image5.png
89
534
media_image5.png
Greyscale
wherein R′″ comprises the cargo. Co-pending 18/282288 further claims wherein each R is independently selected from H and alkyl groups comprising 1-6 C atoms, and wherein R′ is selected from the group consisting of H, aryl groups, and alkyl groups comprising 1-6 C atoms (claim 2); wherein R0 is H, wherein R′ is an alkyl group, wherein R″ is a thioester, and wherein the second chemical structure is according to formula IIIA: wherein X is O or NH, and wherein R1 comprises the cargo (claim 3); wherein the first catalyst is selected from the group comprising riboflavin tetrabutyrate and Ir[dF(CF3)ppy]2(dtbbpy)PF6 (claim 5); wherein the first radiation comprises a first wavelength in the range of 375-525 nm (claim 6); wherein the first stage is executed in a first mixture comprising a first solvent, wherein the first solvent comprises one or more of water, DMSO and DMF (claim 7); wherein the first mixture comprises ≤1 ppm dissolved oxygen (Claim 8); wherein the method further comprises an intermediate stage, wherein the intermediate stage comprises separating the first intermediate from the first reactant (Claim 9); wherein the second stage is performed in a degassed buffer under inert gas(claim 10); wherein the cargo comprises an anti-body (claim 13).
Co-pending 18/282288 Formula I compounds have the same (overlap) the Michael acceptor scaffold but differ in the amide substituent (the SEA functionality). However, Ollivier teaches that SEA is a known peptide ligation handle for reaction with N-terminal cysteine containing peptides. Bloom teaches modifying alpha, beta-unsaturated Michael acceptors to incorporate additional biorthogonal functionalities of subsequent bioconjugation. Raibaut further teaches conventional SEA mediated peptide ligation. Therefore, it would have been obvious to one of ordinary skill in the art to incorporate the known SEA functionality into the Michael acceptor of the co pending claims to enable subsequent peptide ligation, yielding the predictable result of an alternative peptide conjugation reagent. Accordingly, the instant claims are not patentably distinct from the claims of Application No. 18/282288.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ERINNE R DABKOWSKI whose telephone number is (571)272-1829. The examiner can normally be reached Monday-Friday 7:30-5:30 Est.
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, Lianko Garyu can be reached at 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/ERINNE R DABKOWSKI/Primary Examiner, Art Unit 1654
Prosecution Insights