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 does not explicitly state an election with or without traverse. However, the Applicant requests withdrawal of the restriction requirement based on lack of search burden. Therefore, the Applicant’s response will be treated as an election with traverse.
Applicant's election with traverse of Group I (claims 1-15, 19, and 22) and the below listed species in the reply filed on 08/05/2026 is acknowledged.
Applicant elected Group I, drawn to a compound of Formula I or III. For the species within Group I, applicant elected a compound derived from Formula I with the following structure:
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The traversal is on the ground(s) that the restriction requirement is improper because the subject matter of all claims and species is sufficiently related that a thorough search for the subject matter of any one Group of claims or species would encompass a search for the subject matter of the remaining claims and species. Applicant indicates Formula I is shared by all Groups. This is not found persuasive because each invention is under a separate classification. Groups I and II fall under C07D 211/36 and A61P 35/00 respectively. Furthermore, regarding the species of Groups I and II, compounds of Formulas I and III would require different fields of search. Compounds of Formula I would require a search of the chemical structure of the cytotoxic drug while compounds of Formula III would require search of antibody-drug conjugates (ADCs). ADCs have additional parameters such as the number of molecules of the drug and where the drug is bound.
Therefore, each invention and species has attained recognition in the art as a separate subject for inventive effort, and also a separate field of search, showing there would be a serious search and/or examination burden on the examiner if restriction is not required (see MPEP 808.02). Thus, the arguments regarding a lack of search burden are not persuasive.
The requirement is still deemed proper and is therefore made FINAL.
Claim Status
Claims 1-15, 19, and 22 are pending.
Claims 3-4, 10, 16-18, 20-21, and 23-25 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 1-2, 5-9, 11-15, 19, and 22 are currently under consideration for patentability under 37 CFR 1.104.
Priority
This application claims benefit of Provisional U.S. Application Nos. 63/432,470 (filed on 12/14/2022) and 63/497,887 (filed on 04/24/2023). Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Claims 1-2, 5-9, 11-15, 19, and 22 have an effective filing date of 12/14/2022 corresponding to Provisional U.S. Application No. 63/432,470.
Information Disclosure Statement
The information disclosure statements filed on 01/30/2024, 05/03/2024, 09/25/2025, and 02/19/2026 have been considered. Signed copies are enclosed. All references considered unless marked with strikethrough.
Specification
Applicant is reminded of the proper language and format for an abstract of the disclosure.
The abstract should be in narrative form and generally limited to a single paragraph on a separate sheet within the range of 50 to 150 words in length. The abstract should describe the disclosure sufficiently to assist readers in deciding whether there is a need for consulting the full patent text for details.
The language should be clear and concise and should not repeat information given in the title. It should avoid using phrases which can be implied, such as, “The disclosure concerns,” “The disclosure defined by this invention,” “The disclosure describes,” etc. In addition, the form and legal phraseology often used in patent claims, such as “means” and “said,” should be avoided.
Claim Objections
Claims 1 and 8 are objected to because of the following informalities:
Claim 1: “acid acid” should be replaced with “acid”.
Claim 1: the comma after the three pictures depicting R1 options should be replaced with a semicolon.
Claim 8: “auristatin E auristatin F” should be replaced with “auristatin E, auristatin F”.
Claim 8: the extra space before “monomethyl auristatin E” should be deleted.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(a)
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, 5-9, 11-15, and 22 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.
Instant claim 1 is drawn to “[a] compound of Formula I, or a pharmaceutically acceptable salt, solvate, or stereoisomer thereof” (lines 1-2) wherein:
R1 is selected from
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, and
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;
R2 is a cytotoxic drug;
R3 and R4 independently represent C1-3 alkyl or a naturally occurring or unnatural amino acid side chain; and
n is an integer from 1 to 4.
The instant application states “[t]he term ‘cytotoxic drug’ refers to a substance that inhibits or stops the function of cells and/or causes cell death or destruction” (¶ 0098) and “’[u]nnatural amino acid’… refers to an alpha-amino-containing acid or residue thereof, which has the backbone structure of a natural amino acid, but for example has a side chain group attached to the alpha carbon that is not present in natural amino acids” (¶ 0072, emphasis added). A cytotoxic drug is not defined by its structure and instead is given a functional definition of inhibiting cell function or causing cell death; therefore, it is not a specific type of molecule or class, encompassing numerous and diverse cytotoxic drugs. In addition, an unnatural amino acid can have any side chain not found in natural amino acids, giving almost unlimited possibilities for its structure.
Regarding instant claim 6, R2 of the compound of Formula I is further specified as various cytotoxic drugs “selected from auristatin T, auristatin E, auristatin F phenylenediamine, benzolyl-aurstatin E ester, 5-benzoylvaleric acid-AE ester, monomethyl auristatin F, lipophilic monomethyl aurstatin F, monomethyl auristatin E, lexitropsins, duocarmycins, paclitaxel and docetaxel, T67 (Tularik), vincristine, vinblastine, vindesine, vinorelbine, nicotinamide phosphoribosyltranferase inhibitor (NAMPTi), tubulysin M, doxorubicin, morpholino-doxorubicin, cyanomorpholino-doxorubicin, melphalan, methotrexate, mitomycin C, etoposide, CC-1065 analogue, calicheamicin, maytansine, an analog of dolastatin 10, rhizoxin, palytoxin, baccatin derivatives, taxane analogs (e.g., epothilone A and B), nocodazole, colchicine and colcimid, estramustine, cryptophysins, cemadotin, maytansinoids, combretastatins, discodermoide, tesirine and eleuthrobin” (lines 1-10). While Applicant identifies possible R2 cytotoxic drugs, these drugs are numerous and structurally diverse. The instant specification does not provide representative species of compounds of Formula I that incorporate or have common structural characteristics of all recited drugs. Therefore, Applicant has not demonstrated possession of the full genus of drugs encompassed by instant claim 6.
Dependent claims further specify R1 as
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(instant claim 2); R2 as various cytotoxic drugs (instant claims 5-9, 15, and 19); R3 and R4 as C1-3 alkyl, a naturally occurring or unnatural amino acid side chain, or CH3 (instant claims 11-14 and 19); n as the integer 2 (instant claims 14 and 19); and a composition containing the compound and a pharmaceutically acceptable carrier (instant claim 22). Dependent claims collectively demonstrate the high degree of variability within the compound of Formula I, reliant on the identities of the R groups and n integer.
Only instant claim 19 adequately describes the compound of Formula I, giving three species with R groups and n defined, and therefore is not included in this rejection.
US20130309256A1 (published 2013-11-21, hereinafter referred to as US ‘256; IDS filed on 2024-01-30, Cite No. 6 under US Patent Application Publications) teaches examples of cytotoxic drugs including “antitubulin agents, auristatins, DNA minor groove binders, DNA replication inhibitors, alkylating agents (e.g., platinum complexes such as cis-platin, mono(platinum), bis(platinum) and tri-nuclear platinum complexes and carboplatin), anthracyclines, antibiotics, antifolates, antimetabolites, chemotherapy sensitizers, duocarmycins, etoposides, fluorinated pyrimidines, ionophores, lexitropsins, nitrosoureas, platinols, pre-forming compounds, purine antimetabolites, puromycins, radiation sensitizers, steroids, taxanes, topoisomerase inhibitors, [and] vinca alkaloids” (¶ 0255). This teaching exhibits the various and diverse molecules encompassed by the term “cytotoxic drug,” conferring different structures and functions.
US20170182179A1 (published 2017-06-29, hereinafter referred to as US ’179) teaches “[t]he properties of the linker may also impact aggregation of the ADC under conditions of use and/or storage… A linker may incorporate polar or hydrophilic groups such as charged groups or groups that become charged under physiological pH to reduce the aggregation of the ADCs” (¶ 0173). This teaching indicates that choosing a hydrophobic R groups or high n integers in the compound of Formula I could have disastrous effects when implemented in an ADC if not balanced with hydrophilic groups. For example, Shao et al. (Construction of paclitaxel-based antibody–drug conjugates with a PEGylated linker to achieve superior therapeutic index, Sig Transduct Target Ther, 2020) teach the hydrophobic drug paclitaxel can cause precipitation when the linker is also hydrophobic (Pg. 1, entire last ¶ column 1 to first ¶ column 2). Therefore, it is not reasonable to expect all R groups and n values of the compound of Formula I as recited in instant claim 1 to behave equally well in solution.
The compound of Formula I contains two amino acid backbones, wherein their side chains (e.g. R3 and R4) can be from natural or unnatural amino acids. Dal Corso et al. (Protease-Cleavable Linkers Modulate the Anticancer Activity of Noninternalizing Antibody-Drug Conjugates, Bioconjug Chem, 2017) teach dipeptide-based linkers of ADCs and their stability, stating “a single amino acid substitution of the Val–Cit dipeptide linker can substantially modulate the in vivo stability” (Pg. 1826, Abstract, lines 13-14). This teaching illustrates the side chains of the amino acids in a dipeptide-linker influence the functionality of the linker and are sensitive to perturbation. R3 and R4 as recited in instant claim 1 comprise almost infinite structures given the broad definition for an unnatural amino acid side chain. It is not established that all recited R3 and R4 identities retain linker stability nor could a person having ordinary skill in the art predict their structures.
As such, instant claims 1-2, 5-9, 11-15, and 22 are drawn to a genus of compounds of Formula I. The instant specification teaches the three compounds recited in instant claim 19 in Examples 1 (¶ 0185), 2 (¶ 0191), and 3 (¶ 0200). These compounds comprise MMAE as R2, CH3 as R3 and R4, and an n integer of 2. Only the identity of R1 is varied. The instant specification does not provide examples using (i) R2, R3, or R4 groups or (i) n integers outside of those described in instant claim 19 and Examples 1-3 of the instant application.
However, Applicant is claiming a large and structurally diverse genus of compounds of Formula I. Absent empirical determination, one skilled in the art would be unable to immediately envision, recognize, or distinguish at least most of the members comprised within the genus claimed, specifically the structures of the compounds of Formula I. Applicant uses broad definitions to define the genus which is not sufficient as detailed above (US ‘179 and Shao et al. teach the impact of linker hydrophobicity on stability, specifically pertaining to the cytotoxic drug chosen; Dal Corso et al. teach the impact of altering amino acid residues in dipeptide-containing linkers on stability).
Accordingly, Applicant’s disclosure is not sufficient to demonstrate possession of the entire claimed genus and Applicant’s disclosure does not satisfy the written description requirement of 35 U.S.C. 112(a).
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed. The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application, including “the level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention” (MPEP 2163[II][A][2]).
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, disclosure of drawings, or by disclosure of relevant identifying characteristics, for example, 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 Applicants were in possession of the claimed genus.
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. As previously indicated, Applicant has disclosed three species within the genus claimed (i.e. the three compounds as recited in instant claim 19 and Examples 1-3). However, given the large number of species encompassed by the genus claimed as well as the high level of structure variation that would be displayed by members of the claimed genus, the disclosure of three adequately described species is not sufficiently representative of the entire genus.
Although screening techniques can be used to identify stable linkers corresponding to Formula I of the instant application, Applicant is reminded that the written description requirement of 35 U.S.C. 112 is severable from the enablement provision. As stated in Vas-Cath Inc. v. Mahurkar (CA FC) 19 USPQ2d 1111, 935 F2d 1555, “The purpose of the ‘written description’ requirement is broader than to merely explain how to ‘make and use’; the applicant must also 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.”
Accordingly, given the difficulty associated with predicting structures of the compounds of Formula I, and given the lack of particularity with which the genus is described in the specification, it is submitted that the skilled artisan could not immediately envision, recognize, or distinguish at least most of the members of the genus to which the claims are directed, and therefore the instant disclosure fails to demonstrate that Applicant was in possession of the claimed invention at the time the application was filed.
University of California v. Eli Lilly and Co., 43 USPQ2d 1398, 1404. 1405 held that: To fulfill the written description requirement, a patent specification must describe an invention and does so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention.” Lockwood v. American Airlines Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (1997); In re Gosteli , 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus, an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious," and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention" Lockwood, 107 F.3d at 1572, 41 USPQ2datl966.
The specification does not reasonably convey possession of the subject matter of instant claims 1-2, 5-9, 11-15, and 22. Instant claims 1-2, 5-9, 11-15, and 22 fail to comply with the written description requirement of 35 U.S.C. 112(a) as a person having ordinary skill in the art cannot reasonably conclude that the applicant had possession of the claimed invention at the time the instant application was filed.
Only instant claim 19 adequately describes the compound of Formula I, giving three species with R groups and n defined, and is supported by the instant specification. Therefore, instant claim 19 is not included in this rejection.
Claim Rejections - 35 USC § 112(b)
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 6 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.
Regarding claim 6, the phrase "taxane analogs (e.g., epothilone A and B)” renders the claim indefinite because it is unclear whether the limitation in the parentheses of the phrase are part of the claimed invention or merely examples of taxane analogs. See MPEP § 2173.05(d).
For the purposes of claim interpretation, the limitation in the parentheses will be treated as examples of taxane analogs and not part of the claimed invention.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 13 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. Claim 1 recites R3 and R4 can be naturally occurring or non-naturally occurring amino acid side chains. Claim 13, dependent on claim 1, recites R3 and R4 can be naturally occurring or non-naturally occurring amino acid residues. Therefore, claim 13 fails to include all the limitations of claim 1 as amino acid residues encompass an amino group, a carboxyl group, and an alpha carbon in addition to a side chain. Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
For the purposes of claim interpretation, the phrase “amino acid residue” in claim 13 will be interpreted as “amino acid side chain.”
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.
Claims 1-2, 5-9, 11-15, 19, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over US20170182179A1 (published 2017-06-29, hereinafter referred to as US ’179) in view of US20130309256A1 (published 2013-11-21, hereinafter referred to as US ‘256; IDS filed on 2024-01-30, Cite No. 6 under US Patent Application Publications).
US ‘179 teaches methods of making “Antibody Drug Conjugates (ADCs)” (Abstract). Regarding n, R1, R3, and R4 of the compound of Formula I as recited in instant claims 1-2, 11-14, and 19, US ‘179 teaches “exemplary embodiments of linkers… that may be included in the ADCs” (¶ 0148), illustrating the molecule below (¶ 0148, molecule labeled IVb.6 ). Please note the molecule is flipped along its horizontal axis when compared to the elected species of the instant application; molecule IVb.6 is identical to the elected species without R2.
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R1 is
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(instant claims 1-2, 14, and 19);
n is equal to 2 (instant claims 1, 14, and 19);
R3 and R4 are both C1 alkyl groups (instant claim 11) i.e. CH3 (instant claim 12) side chains of the naturally occurring amino acid alanine (instant claims 1, 13-14, and 19).
Regarding instant claim 22, US ‘179 further teaches “ADC compositions may be supplied as part of a sterile, pharmaceutical composition that includes a pharmaceutically acceptable carrier” (¶ 0384), reading on a composition comprising the compound and a pharmaceutically acceptable carrier.
US ‘179 further teaches “auristatin/auristatin family members” can be the linking drugs in ADCs (¶ 0124). US ‘179 further teaches “the linker comprises an enzymatically cleavable peptide moiety” (¶ 0134, indicates linkers of formulas IVb are cleavable) to release the drug. These teachings give motivation for attaching auristatin to the linker IVb.6 as the linker has a peptide moiety that can cause release of auristatin for therapeutic purposes i.e. delivery of the drug.
US ‘179 does not teach the linker IVb.6 covalently attached to MMAE, corresponding to R2 as recited in instant claims 1, 5-9. 14-15, 19. This deficiency is remedied by US ‘256.
US ‘256 teaches methods of making “Ligand-Drug Conjugates” (Abstract), also referred to as ADCs. Regarding R2 as recited in instant claims 1, 5-9. 14-15, 19, US ‘256 further teaches ADCs comprising the cytotoxic drug MMAE (¶ 0260, indicates the auristatin drug MMAE can be used in an ADC to “bind tubulin and exert a cytotoxic or cytostatic effect” i.e. it is a cytotoxic drug). This teaching reads on R2 is the cytotoxic drug (instant claims 1 and 14) auristatin (instant claim 5 and 7), specifically MMAE (instant claims 6, 8-9, 15, and 19).
US ‘256 further teaches ADCs comprising an “unsubstituted PAB [p-aminobenzyl alcohol] unit” with the structure below (¶ 0328). Note the PAB unit is identical to the righthand side of the linker IVb.6 taught by US ‘179.
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US ‘256 further teaches ADCs containing PAB can be modified to include MMAE, producing PAB-MMAE (Example 2, ¶ 0495-0498, discusses synthesis of ADC named Val-Cit-PAB-MMAE). This teaching gives motivation for modifying the PAB of the molecule IVb.6 taught by US ‘179 to PAB-MMAE.
US ‘256 further teaches PAB linkers are cleavable (¶ 0325, teaches PAB spacers are self- immolative i.e. cleavable), giving motivation for using a PAB linker as it would release the drug from the antibody for delivery.
US ‘256 does not teach n, R1, R3, and R4 of the compound of Formula I as recited in instant claims 1-2, 11-14, and 19. This deficiency is remedied by US ‘179.
PAB-containing linkers of ADCs were known and used prior to the effective filing date of the application. In addition, both US ‘179 and US ‘256 are in analogous arts (i.e. ADCs wherein the drug is an auristatin). Since US ‘256 teach (i) PAB-containing linkers can be modified to produce PAB-MMAE-containing linkers and (ii) PAB-containing linkers are cleavable, facilitating the release of the drug from the antibody for delivery, there is motivation for conjugating the PAB-containing linker IVb.6 as taught by US ‘179 to MMAE as taught by US ‘256 in order to obtain an ADC that can release the cytotoxic drug MMAE following the cleavage of the PAB-containing linker.
MPEP § 2141(III)(G) states a rationale that may support a conclusion of obviousness includes “[s]ome teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention.” MPEP § 2143(I)(G) states this rationale should explain why “[a] person of ordinary skill in the art would have been motivated to combine the prior art to achieve the claimed invention and whether there would have been a reasonable expectation of success in doing so." DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 464 F.3d 1356, 1360, 80 USPQ2d 1641, 1645 (Fed. Cir. 2006).
The teaching, suggestion, or motivation in the prior art (i.e. US ‘256 teach PAB-containing linkers can be modified to produce PAB-MMAE-containing linkers) would have led one of ordinary skill to modify the prior art reference (i.e. the PAB-containing linker IVb.6 as taught by US ‘179) to arrive at the claimed invention. PAB-containing linkers of ADCs were known and used prior to the effective filing date of the application as they are cleavable for release of the cytotoxic payload. US ‘256 identifies MMAE as a suitable cytotoxic payload for a PAB-containing linker. As US ‘179 teaches the linker IVb.6 contains PAB and identifies auristatins as suitable drugs for its payload, there is a reasonable expectation of success that conjugation of the auristatin MMAE to the linker IVb.6 would produce a functional linker capable of releasing MMAE for therapeutic delivery of the drug. In addition, both US ‘179 and US ‘256 are in analogous arts (i.e. ADCs wherein the drug is an auristatin).
It would have been obvious to a person having ordinary skill in the art prior to the effective filing date of the instant application to conjugate the PAB-containing linker IVb.6 as taught by US ‘179 to MMAE as taught by US ‘256 in order to obtain an ADC that can release the cytotoxic drug MMAE following the cleavage of the PAB-containing linker.
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 1-2, 5-9, 11-15, 19, and 22 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 9, 13, and 17 of copending Application No. 18/642,038 (reference application, hereinafter referred to as copending ‘038). Although the claims at issue are not identical, they are not patentably distinct from each other.
Claims 9 and 17 of copending ‘038 teach ADCs containing a linker-MMAE named MP-AA-PABC-MMAE, depicted below. MP-AA-PABC-MMAE is identical to the elected species of the instant application.
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This teaching reads on:
R1 is
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104
82
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(instant claims 1-2, 14, and 19);
R2 is the cytotoxic drug auristatin (instant claim 1, 5, 7, and 14), specifically MMAE (instant claims 6, 8-9, 15, and 19);
n is equal to 2 (instant claims 1, 14, and 19);
R3 and R4 are both C1 alkyl groups (instant claim 11) i.e. CH3 (instant claim 12) side chains of the naturally occurring amino acid alanine (instant claims 1, 13-14, and 19).
Claim 13 of copending ‘038 teaches a composition of the ADC and a pharmaceutically acceptable carrier. As the ADC contains the compound of Formula I of the instant application, this teaching reads on a composition comprising the compound of Formula I and a pharmaceutically acceptable carrier (instant claim 22).
As delineated above, claims 9, 13, and 17 of copending ‘038 teach all limitations of instant claims 1-2, 5-9, 11-15, 19, and 22 regarding a compound of Formula I, rendering the instant claims obvious. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
Claims 1-2, 5-9, 11-15, 19, and 22 are currently under consideration for patentability under 37 CFR 1.104. Claims 1 and 8 is objected to. Claims 1-2, 5-9, 11-15, 19, and 22 are rejected. No claims are allowed.
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/J.M.P./Examiner, Art Unit 1642
/SAMIRA J JEAN-LOUIS/Supervisory Patent Examiner, Art Unit 1642
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