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 II in the reply filed on November 19, 2025 and a species for the linker of
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in the reply of February 4, 2026 is acknowledged. The elected linker can also be described as a conjugate of 6-amino hexanoic acid-Gly-Arg-Lys(N3).
The requirement is still deemed proper and is therefore made FINAL.
The election of auristatin as a payload in the response of February 4, 2026 is acknowledged. It would appear that the presence of B2 as second linking moiety or payload as part of the linker, as set forth in withdrawn claim 82, might allow for the presence of auristatin as a payload in the linker Aax-(Sp1)-B1-(Sp2). However, no B2 is present in elected species in which Applicants have clearly set forth complete structures for Aax, (Sp1), (Sp2) and B1 that does not comprise B2.
Comments and Notes
For exact antecedent basis, it is respectfully suggested that “for crosslinking” be added after “non-bio-orthogonal entity” in line 2 of claim 84.
Specification
The disclosure is objected to because of the following informalities:
There are also numerous abbreviations such as BCN, ADIBO and DBCO that are never accompanied by the complete term the first time they are used. Please review the disclosure in its entirety and address each instance in which an abbreviation is not accompanied by the complete terminology the first time they appear and make the appropriate corrections.
The abbreviation “PROTAC” is used in the specification which appears to stand for “proteolysis targeting chimera” rather than an abbreviation for “protein degradation agent” but based on the formatting, it appears that PROTAC could be Applicants’ abbreviation for the genus of protein degradation agent. Appropriate correction is also required by either indicating that PROTAC refers to “proteolysis targeting chimera” or is being used as an abbreviation for “protein degradation agent”.
Improper Markush Grouping of Alternatives
Claims 36 – 38, 41, 48, 64, 77 – 81, 83 and 84 are rejected on the 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). A Markush grouping is proper if the alternatives defined by the Markush group (i.e., alternatives from which a selection is to be made in the context of a combination or process, or alternative chemical compounds as a whole) share a “single structural similarity” and a common use. A Markush grouping meets these requirements in two situations. First, a Markush grouping is proper if the alternatives are all members of the same recognized physical or chemical class or the same art-recognized class, and are disclosed in the specification or known in the art to be functionally equivalent and have a common use. Second, where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the alternatives do not belong to a recognized class as set forth above, the members of the Markush grouping may be considered to share a “single structural similarity” and common use where the alternatives share both a substantial structural feature and a common use that flows from the substantial structural feature. See MPEP § 2117.
The Markush grouping of claims 36 and 37 is improper because the alternatives defined by the Markush grouping do not share both a single structural similarity and a common use for the following reasons: the linkers do not belong to the same recognized physical or chemical class or the same art-recognized class, and are not disclosed in the specification or known in the art to be functionally equivalent and have a common use. The only required structural similarity of the compounds in the claimed Markush group is a primary amine in the linker that is used for conjugation to a glutamine residue in an antibody. That group when viewed in the context of the claimed antibody-linker conjugate is not a substantial structural feature. Therefore the Markush group is not a proper grouping. None of the dependent claims limit the claim scope to a proper Markush group that meets the necessary criteria.
To overcome this rejection, Applicant may set forth each alternative (or grouping of patentably indistinct alternatives) within an improper Markush grouping in a series of independent or dependent claims and/or present convincing arguments that the group members recited in the alternative within a single claim in fact share a single structural similarity as well as a common use.
Claim Rejections - 35 USC § 112 – Written Description
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 36 – 38, 41, 48, 64, 77 – 81, 83, and 84 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 claims very broadly define a linker structure, Aax-(Sp1)-B1-(Sp2), Aax being an amino acid with a primary amine, that is conjugated via that primary amine to a glutamine residue in an antibody. Claim 36 is a product-by-process claim in which the conjugation to the glutamine of the antibody is accomplished using a microbial transglutaminase mediated method in which the conjugation reaction takes place enzymatically so the linker must be suitable as an enzymatic substrate for such a reaction. Claim 37 is not a product-by-process claim as the claimed antibody-linker conjugate is claimed with no limitations on the process by which it was made but the structure of the linker is the same as that of claim 36.
A generic claim may define the boundaries of a vast genus of chemical compounds, and yet the question may still remain whether the specification, including original claim language, demonstrates that the applicant has invented species sufficient to support a claim to a genus. The problem is especially acute with genus claims that use functional language to define boundaries of a claimed genus. In such a case, the functional claim may simply claim a desired result, and may do so without describing species that achieve that result. But the specification must demonstrate that the applicant has made a generic invention the achieves the claimed results and do so by showing that that the applicant has invented species sufficient to support a claim to a functionally-defined genus. Disclosure of every species within a genus is not required, as a representative number of species within the claimed genus can be sufficient to demonstrate possession of the entire genus claimed.
With the exception of the primary amine of the linker used for conjugation to the glutamine of the antibody, the structure is very broadly defined by function - spacer, linker or payload. An amino acid does require the presence of both an amino group and carboxylic acid but is otherwise very broad. Dependent claims specify that spacers can be amino acids and possible or excluded charges for the linker but no specific structures or sequences are given. Even when a biorthogonal marker group or non-bio-orthogonal entity for crosslinking is required, most of the possible functional groups are recited at high levels of generality (e.g., -N-N=N, strained alkene or -SH) and such groups can be located anywhere within the claimed Aax-(Sp1)-B1-(Sp2) linker. When B1 is a payload, the possible functions and structures of the payload are also very broad (see withdrawn claim 87).
Figure 2 of the disclosure as originally filed shows complete structures for 14 linkers that are generally pretty similar in structure to one another and represent a very small number of species within the very large genus being claimed. Therefore the disclosed linkers do not constitute a representative number of species within the claimed genus to provide adequate support for the complete breadth of the claims. None of the dependent claims add sufficient limitations to make the disclosed structures a representative number of species to satisfy the written description requirement.
Claim Rejections - 35 USC § 112 – Indefiniteness
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.
Claim 46 is 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.
It appears that this claim contains a broad range or limitation together with a narrow range or limitation that falls within the broad range or limitation (in the same claim) may be considered indefinite if the resulting claim does not clearly set forth the metes and bounds of the patent protection desired. See MPEP § 2173.05(c). From a review of the art, it appears that PROTAC stands for “proteolysis targeting chimera” which would be a narrower statement of the genus of “a protein degradation agent”. The claim(s) are considered indefinite because there is a question or doubt as to whether the feature introduced by such narrower language is (a) merely exemplary of the remainder of the claim, and therefore not required, or (b) a required feature of the claims. Alternatively, if PROTAC is being used as the abbreviation for a protein degradation, that must be clarified as while Applicants can act as their own lexicographer, they must clearly redefine the term and that has not been done and also without introducing new matter into the disclosure as originally filed. Please clarify.
Claim Rejections - 35 USC § 102
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.
Claim(s) 36, 37, 41, 48, 64, 77 – 81, 83 and 84 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Spycher et al. (WO 2019/057772; cited on IDS filed July 27, 2023).
Spycher et al. discloses methods and linker structures for generating antibody-payload conjugates using a microbial transglutaminase (MTG) (whole document, e.g., p 4, ¶ 1). Linkers comprising primary amines of the formula
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as defined on p 14 are disclosed as being suitable for such methods. The Aax-NH2 group can be lysine, a derivative or mimetic thereof (p 15, ¶ 4 onward). The net charge of the linker can be neutral or positive (p 23, ¶ 1). B can be a linking moiety with, in some embodiments, a further step of linking the actual payload to the linking moiety (p 24, ¶ 7). B can be a biorthogonal marker group or other non-bio-orthogonal entities for crosslinking with the former referring to reactive groups that can lead to chemical reaction occurring inside of living systems without interfering with native biochemical processes (p 25, ¶ 5 onward). Pages 26 and 27 provide specific examples of functional groups that fall within these genera. Linkers such as the first structure shown in Figure 18A comprise multiple amino acids with an azide for click chemistry, no negatively charged amino acids but neutral or positive amino acids are present, reading on the linkers of the instant claims. Pharmaceutical compositions comprising the linker, linker-payload or antibody-payload conjugate (e.g., p 35, ¶ 3) are also disclosed.
Claim(s) 36 – 8, 41, 48, 64, 78 – 81, 83 and 84 are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Schibli et al. (WO 2020/188061; cited on IDS filed July 27, 2023). This rejection is based on art which was found incidental to the search for the elected species.
Schibli et al. discloses antibody-payload conjugates generated using MTG with a linker Gly-(Aax)m-B-(Aax)n via the N-terminal primary amine of the N-terminal glycine (Gly) residue to a glutamine (Gln) residue comprised in the heavy or light chain of an antibody (whole document, e.g., abstract). B can be a payload or linking moiety (p 14, ¶ 3). The peptide linking moiety of Figures 7A and 7B comprises bio-orthogonal linking moieties (azide (N3) or tetrazine) that can be clicked simultaneously that allow for the conjugation of two different payloads to the Q295 of the CH2 domain of an antibody (see also p 7, ¶ 1 onward). The linker can comprise positively charged amino acids and cannot comprise negatively charged amino acid residues in some embodiments (p 28). Some exemplary amino acid sequences are disclosed on p 30, ¶ 3 and Table 8 (p 72). Pharmaceutical compositions of the linker, linker-payload construct and/or the antibody-payload conjugated are also disclosed (p 60, ¶ 3).
Claim Rejections - 35 USC § 103
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.
Claim(s) 36 – 38, 41, 48, 64, 77 – 81, 83, 84 and 91 are rejected under 35 U.S.C. 103 as being unpatentable over Spycher et al. (WO 2019/057772; cited on IDS filed July 27, 2023) in view of Kamiya et al. (Org Biomol Chem, 2009).
In addition to the teachings of Spycher et al. discussed above, Spycher et al. discloses that the Aax residues can be any natural or non-naturally occurring L- or D- amino acid, amino acid derivative or mimetic (p 14, bottom of page). The list of non-natural amino acids on p 19, ¶ 3 includes 6-aminohexanoic acid, which is the first segment Aax of the elected species. The linker can also comprise at least two amino acids selected from the group consisting of lysine, derivatives or mimetics of lysine; arginine and/or histidine (p 23, middle of page). Lys(N3), also referred to as N3, can be regarded as the linking moiety B and is suitable for click chemistry (¶ bridging p 4 and 5). Additional discussion as to the presence of at least one of a biorthogonal marker group and other non-bio-orthogonal entities for crosslinking is present beginning in the middle of p 25. Specific functional groups falling within the scope of these terms is given on p 26 with reactive pairs being set forth in the table bridging p 26 and 27.
Motivation to select 6-aminohexanoic acid, also known as ε-aminocaproic acid or ε-Acp is not set forth.
Kamiya et al. studied various small substrate for the covalent labeling of protein catalyzed by microbial transglutaminase (MTG; whole document, e.g., abstract). The insertion of a linker such as ß-alanine (ß-Ala) allowed for a reaction to occur when no reaction was seen for MTG-mediated labeling in the absence of the linker (p 3408, col 1, ¶ 4). Constructs with the longer ε-aminocaproic acid linker were also studied (p 3408, col 2, ¶ 1). The results showed that linker length and the fluorescent moiety structure affected MTG substrate recognition (p 3410, col 1, ¶ 1). There is a tradeoff between the flexibility of the enzyme and its substrate specificity that will be an important consideration in the application of TGase (transglutaminase; ¶ bridging cols 1 and 2 on p 3410).
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to select a terminal 6-aminohexanoic acid non-natural amino acid as the terminal residue of a peptidic linker as disclosed by Spycher et al. that comprises glycine, arginine and click chemistry ready Lys(N3) group. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the materials of Spycher et al. are substrates for MTG and based on the knowledge of one of ordinary skill in the art and the teachings of Kamiya et al., factors such as the linker length and the rest of the material to be attached using the transglutaminase reaction. 6-aminohexanoic acid is amongst the non-natural amino acids disclosed by Spycher et al. and can provide a longer linker that can result in molecules being substrates for TGases that would not otherwise undergo the reaction or alter the reaction kinetics as taught by Kamiya et al. The lysine derivative suitable for click chemistry is useful for further conjugation of molecules in a highly selective manner that can occur after conjugation of the linker to the antibody or even possibly inside of living systems without interfering with native biochemical processes. The other amino acids in the linker can alter the overall length of the linker and properties such as the charge with glycine and arginine both being disclosed by Spycher et al. in various linkers. There is no evidence of record as to the criticality of the elected linker species of 6-aminohexanoic acid-Gly-Arg-Lys(N3).
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 36 – 38, 41, 48, 64, 77 – 81, 83 and 84 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 51, 52, 76, 77 and 94 – 126 of copending Application No. 17/435,356 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US’356 recite an antibody-payload conjugate comprising a linker of
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as defined in claim 51 conjugated to a glutamine residue of an antibody via the N-terminal primary amine of the glycine residue. B can be a payload or linker with a payload covalently or non-covalently bound to the linking moiety (claim 51) and can comprise a biorthogonal marker groups or non-bio-orthogonal entities for crosslinking (claim 96). Specific examples of such groups are recited in claim 97. Claims 76 and 77 are drawn to pharmaceutical compositions of the antibody-payload conjugate. Specific amino acid containing linkers are set forth in claim 117. These overlap with the conjugates of the instant claims such that the instant claims are not patentably distinguished over the claims of US’821.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 36 – 38, 41, 48, 64, 77 – 81, 83 and 84 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 117 – 136 of copending Application No. 18/630,281 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US’281 recite antibodies conjugate via a glutamine residue to a linker of formula
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as defined in claim 117 where the spacers (Sp) are all optional and B is a linking moiety or payload. R and K are amino acids and have a primary amine as required by the instant claims. When B is a linking moiety, biorthogonal marker groups or non-bio-orthogonal entities for crosslinking can be present (claims 120 – 122) or a payload such as those of claims 125 and 126. These overlap with the conjugates of the instant claims such that the instant claims are not patentably distinguished over the claims of US’821.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 36 – 38, 41, 48, 64, 77 – 81, 83 and 84 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 4, 6 – 10, 13 – 16, 18, 19, 21, 24, 28, 29 and 33 of copending Application No. 18/639,584 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US’584 recite a method of making an antibody-linker conjugate (claim 1), the antibody-linker conjugate produced by such a method (claim 29) and a method in which the antibody-linker conjugate is administered to a patient (claim 33). The linker of formula
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is conjugated to the Gln residue of the antibody via a primary amine in the lysine side chain present in the linker (claim 1). The formula is defined in claim 1 and the spacers (Sp) are all optional and B is a linking moiety or payload. When B is a linking moiety, biorthogonal marker groups or non-bio-orthogonal entities for crosslinking can be present (claims 13 and 14) or a payload such as those of claims 18 and 19. These overlap with the conjugates of the instant claims such that the instant claims are not patentably distinguished over the claims of US’584.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 36 – 38, 41, 48, 64, 77 – 81, 83 and 84 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 77 – 83, 86 – 90, 93, 96 – 100, 107 and 117 of copending Application No. 18/780,902 (reference application) optionally further in view of Spycher et al. (WO 2019/05772). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US’902 recite a linker of structure
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(claim 77) wherein the spacers (Sp) are all optional and B is a linking moiety or payload. R and K are amino acids and have a primary amine as required by the instant claims. The same linker as in claim 77 can also be conjugated to Q295 glutamine side chain of the antibody and a primary amine group in the linker in claim 117. Antibody-drug conjugated with amino acid linkers of RKAA, RKA, ARK, RKR or RK-Val-Cit and drug moiety B using the Q295 glutamine side chain in an antibody and a primary amine group in the linker (claim 107). These overlap with the conjugates of the instant claims such that the instant claims are not patentably distinguished over the claims of US’902.
That the linker comprises a biorthogonal marker group or non-bio-orthogonal entity for crosslinking is not specifically claimed.
Spycher et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate biorthogonal marker group or non-bio-orthogonal entity for crosslinking into the conjugates of US’902. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the presence of such groups on the linker it taught by Spycher et al. and will enable further conjugation of molecules in a highly selective manner that can occur after conjugation of the linker to the antibody or even possibly inside of living systems without interfering with native biochemical processes due to the nature of these groups.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 36 – 38, 41, 48, 64, 77 – 81, 83 and 84 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 10, 20, 22, 23, 29, 30, 33, 35, 38, 39, 41, 44, 70 and 82 of copending Application No. 18/803,344 (reference application) further in view of Spycher et al. (WO 2019/05772). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US’344 recite linker with an amino acid having a primary amino and two or more payloads being attached at either terminus of the peptide or the side chain of an amino acid in the linker (claim 1). That linker can be conjugated to an antibody (claim 29) such as to a glutamine residue in the antibody via the primary amine in the peptide linker (claim 30). These overlap with the conjugates of the instant claims such that the instant claims are not patentably distinguished over the claims of US’344.
That the linker comprises a biorthogonal marker group or non-bio-orthogonal entity for crosslinking is not specifically claimed.
Spycher et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate biorthogonal marker group or non-bio-orthogonal entity for crosslinking into the conjugates of US’344. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the presence of such groups on the linker it taught by Spycher et al. and will enable further conjugation of molecules in a highly selective manner that can occur after conjugation of the linker to the antibody or even possibly inside of living systems without interfering with native biochemical processes due to the nature of these groups.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 36 – 38, 41, 48, 64, 77 – 81, 83 and 84 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 5, 7 – 9, 12, 13, 15 and 18 - 26 of copending Application No. 19/389,744 (reference application) further in view of Spycher et al. (WO 2019/05772). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US’744 recite a method that uses an antibody drug conjugate with payloads of a cytotoxic molecule and a tumor-targeting small molecule (claim 1) that can have the formula (antibody or antibody fragment)-(linker comprising the cytotoxic molecule and a tumor-targeting small molecule) (claim 7) that can be conjugated via a glutamine residue in the antibody (e.g., claim 8) such as by a lysine residue, cadaverine moiety or PEG amine moiety (claim 12), all of which comprise a primary amine. These overlap with the conjugates of the instant claims such that the instant claims are not patentably distinguished over the claims of US’744.
That the linker comprises a biorthogonal marker group or non-bio-orthogonal entity for crosslinking is not specifically claimed.
Spycher et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate biorthogonal marker group or non-bio-orthogonal entity for crosslinking into the conjugates of US’744. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the presence of such groups on the linker it taught by Spycher et al. and will enable further conjugation of molecules in a highly selective manner that can occur after conjugation of the linker to the antibody or even possibly inside of living systems without interfering with native biochemical processes due to the nature of these groups.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Claims 36 – 38, 41, 48, 64, 77 – 81, 83 and 84 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 23 of U.S. Patent No. 11,396,649. Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US’649 recite a method that results in the conjugation of a peptide linker comprising a lysine and/or glutamine residue to an antibody or antigen-binding fragment thereof using MTG (claim 1). Exemplary linkers are given in claim 7 and the peptide linker can also comprise a payload molecule selected from the Markush group of claim 5. Reactive groups suitable for click chemistry (claim 14) can be present, reading on a biorthogonal marker group or non-bio-orthogonal entity for crosslinking. These overlap with the conjugates of the instant claims such that the instant claims are not patentably distinguished over the claims of US’649.
Claims 36 – 38, 41, 64 and 77 – 81 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 – 10, 12 – 15 and 17 - 23 of U.S. Patent No. 12,076,412 optionally further in view of Spycher et al. (WO 2019/05772). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US’412 recite an antibody drug conjugate of an IgG antibody with a toxin drug moiety B covalently conjugated with RKAA, RKA, ARK, RKR or RK-Val-Cit and drug moiety B using the Q295 glutamine side chain in an antibody and a primary amine group from the lysine residue in the linker (claim 1). These overlap with the conjugates of the instant claims such that the instant claims are not patentably distinguished over the claims of US’412.
That the linker comprises a biorthogonal marker group or non-bio-orthogonal entity for crosslinking is not specifically claimed.
Spycher et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate biorthogonal marker group or non-bio-orthogonal entity for crosslinking into the conjugates of US’412. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the presence of such groups on the linker it taught by Spycher et al. and will enable further conjugation of molecules in a highly selective manner that can occur after conjugation of the linker to the antibody or even possibly inside of living systems without interfering with native biochemical processes due to the nature of these groups.
Claims 36 – 38, 41, 48, 64, 77 – 81, 83 and 84 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1 - 31 of U.S. Patent No. 12,128,110 optionally further in view of Spycher et al. (WO 2019/05772). Although the claims at issue are not identical, they are not patentably distinct from each other because the claims of US’110 recite an antibody conjugate with a linker construct of
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as defined in claim 1 conjugated to the glutamine residue Q295 of antibody via the primary amine group of the Aax-NH2 group (claim 1). B can be a payload (see claims 6 – 9) or a linker. These overlap with the conjugates of the instant claims such that the instant claims are not patentably distinguished over the claims of US’110.
Claims 19 and 20 recite that the linker and/or payload are chemically modified during binding or conjugation to allow covalent or non-covalent binding to form said constructs, that the linker comprises a biorthogonal marker group or non-bio-orthogonal entity for crosslinking is not specifically claimed.
That the linker comprises a biorthogonal marker group or non-bio-orthogonal entity for crosslinking is not specifically claimed.
Spycher et al. is discussed above.
It would have been obvious to the person of ordinary skill in the art before the effective filing date of the claimed invention to incorporate biorthogonal marker group or non-bio-orthogonal entity for crosslinking into the conjugates of US’110. The person of ordinary skill in the art would have been motivated to make those modifications and reasonably would have expected success because the presence of such groups on the linker it taught by Spycher et al. and will enable further conjugation of molecules in a highly selective manner that can occur after conjugation of the linker to the antibody or even possibly inside of living systems without interfering with native biochemical processes due to the nature of these groups.
Conclusion
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/Nissa M Westerberg/Primary Examiner, Art Unit 1618
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