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 .
Priority
This application, filed 03/16/2023 Claims Priority from Provisional Application 63407609, filed 09/16/2022; and from Provisional Application 63321105, filed 03/17/2022.
Status of Claims
Claims 1-2, 4, 17-19, 31-32, 34, 46-47, 54-56, 61, 63, 65, 72-73, 76, 79, 83-84 are pending as of the response filed on 3/20/26. Claims 3, 5-16, 20-30, 33, 35-45, 48-53, 57-60, 62, 64, 66-71, 74-75, 77-78, 80-82, and 85 have been canceled.
Applicant’s election without traverse of the camptothecin linker compound shown below in the reply filed on 3/20/26 is acknowledged:
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. Applicants have stated the elected compound reads directly on claims 31-32, 34, 46-47, and 76, and comprises the Q-D moiety of claims 1-2, 4, 17-19, 61, 63, and 79. However, the examiner notes that the above shown compound doesn’t contain the ligand unit L which is required for claims 1-2, 4, 17-19, 61, 63, and 79.
In addition to the elected species, search and examination have been extended to the following two species in accordance with MPEP 803.02, in an effort to provide compact prosecution, with the understanding that the species election is not withdrawn:
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; and
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. These additional species are encompassed by claims 65, 73, and 84.
Claims 1-2, 4, 17-19, 54-56, 61, 72, 79, and 83 are withdrawn from current examination, being drawn to a non-elected species. Claims 31-32, 34, 46-47, 65, 73, 76, and 84 are currently under examination.
Claims 31-32, 34, 46-47, 65, 73, 76, and 84 were examined and are rejected.
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 31-32, 34, and 46-47 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.
Independent claim 31 recites limitation wherein Z’ is a stretcher unit precursor; A is a bond or connector unit; B is a parallel connector unit; S* is a partitioning unit; RL is a releasable linker; and Y is a spacer unit. However, these recitations in the claim are vague and do not provide specific structural limitations to these units. No specific chemical formulas, functional groups, or structural qualifications are recited in the claim with respect to Z’, A, B, S*, RL, and Y. Based on the vague and unclear recitations with respect to these units, it’s unclear how in fact each unit is distinguishable from the other, for example, how does Z’ differ structurally from B, Y, or S*? The metes and bounds of the claim are unclear as it’s not certain what is actually meant and encompassed by Z’, A, B, S*, RL, and Y. Claims 32, 34, and 46-47 are similarly rejected as these claims depend from claim 31 and don’t provide further clarity.
Claim 34 is further rejected for reciting a limitation that lacks antecedent basis from the claim it indirectly depends from, claim 31. Claim 34 recites the camptothecin-linker to be selected from several formulas, and recites for example X can be CRxRx’:
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. However, the ring containing X would then be a carbocyclic ring, while claim 31 specifies that this fused ring formed by Rb2 with Rb3 and intervening atoms to be a heterocyclo. The claim is indefinite since it claims limitations which are excluded by independent claim 31. Additionally, the formulas recite substituents Rc1 and Rc2 for the fused ring formed by Rb2 with Rb3 and intervening atoms, wherein Rc1, Rc2 can be numerous functional groups in addition to hydrogen, however, claim 31 doesn’t recite the fused ring to be optionally further substituted. Thus, there is insufficient antecedent basis for these limitations as well.
Claim 47 is further indefinite for reciting broad and narrow limitations. Claim 47 recites RL is a glycoside, which is then followed by “(e.g., Glucuronide) Unit”. It is uncertain if the claim is limited to the broad recitation or the narrow recitation.
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.
Claim(s) 65 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Miyasaka et. al, US 4399282, patented 8/16/1983.
Miyasaka discloses the compound 7-hydroxymethylcamptothecin (title & abstract; col. 4, lines 38-43; col. 16, Ex. 1, lines 37-68):
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. This compound is included in Formula D0b of claim 65, having E=-ORb5; Rb5=H; Rb1, Rb2, Rb3, Rb4, and Rb6=H. Miyasaka therefore anticipates the claims.
(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) 65, 73, and 84 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Jeffrey et. al., WO 2022198232 A1, publ. 9/22/2022 (claims priority to provisional application 61163008, filed on 3/18/2021, which provides support to the compound shown below), cited in the IDS, hereafter referred to as ‘Jeffrey 2’.
The applied reference has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2). This rejection under 35 U.S.C. 102(a)(2) might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C. 102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B) if the same invention is not being claimed; or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed in the reference and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement.
Jeffrey 2 discloses the following compound (title & abstract; p. 253, para [0605], compound 2n):
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. This compound is recited in claim 73, and is included within formula D0b of claim 65, having: E=-NRb5Rb5’; Rb5, Rb5’=H; Rb2 and Rb3 combine together to form a fused tetrahydrofuran ring; and Rb1, Rb4, and Rb6=H. Jeffrey 2 therefore anticipates the claims.
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) 31-32, 34, 46-47, and 76 is/are rejected under 35 U.S.C. 103 as being unpatentable over Jeffrey et. al., WO 2019236954 A1, publ. 12/12/2019, cited in the IDS, in view of Jeffrey et. al., WO 2022198232 A1, publ. 9/22/2022 (claims priority to provisional application 61163008, filed on 3/18/2021), cited in the IDS, hereafter referred to as ‘Jeffrey 2’.
The applied reference, Jeffrey 2 has a common inventor with the instant application. Based upon the earlier effectively filed date of the reference, it constitutes prior art under 35 U.S.C. 102(a)(2).
This rejection under 35 U.S.C. 103 might be overcome by: (1) a showing under 37 CFR 1.130(a) that the subject matter disclosed in the reference was obtained directly or indirectly from the inventor or a joint inventor of this application and is thus not prior art in accordance with 35 U.S.C.102(b)(2)(A); (2) a showing under 37 CFR 1.130(b) of a prior public disclosure under 35 U.S.C. 102(b)(2)(B); or (3) a statement pursuant to 35 U.S.C. 102(b)(2)(C) establishing that, not later than the effective filing date of the claimed invention, the subject matter disclosed and the claimed invention were either owned by the same person or subject to an obligation of assignment to the same person or subject to a joint research agreement. See generally MPEP § 717.02.
Jeffrey teaches camptothecin conjugates composed of camptothecin derivatives that are ultimately conjugated to antibodies (title & abstract). Jeffrey teaches antibody drug conjugates (ADCs) to be composed of cytotoxic drugs attached covalently to an antibody, which can be used to deliver the cytotoxic drugs to tumor cells (para [0002-0003]). Jeffrey teaches a variety of camptothecin derivatives which are attached covalently via an antibody via a Q linker unit, which is selected from one of the formulas shown below (para [0005]):
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. Jeffrey teaches it is desirable to synthesize the cytotoxic drug-linker prior to conjugation to a targeting agent, e.g., antibody (para [0158]). Jeffrey teaches embodiments wherein RL is a glucuronide as shown, wherein the sugar moiety is linked via a glycosidic bond to a self-immolative spacer unit (para [0263-0264], [0273]):
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, wherein the wavy line attached to -NH- represents a point of attachment to a stretcher unit or stretcher unit precursor either directly or through connection via the parallel connector unit B. The hash mark in the above shown structure represents covalent attachment point to a spacer unit or functional group of the camptothecin derivative. Jeffrey provides the following exemplary camptothecin-linker compound (para [0919], [0942]):
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. For the above shown compounds, the linker attached to the camptothecin derivative via a -NH-CH2- functional group attached to the camptothecin core is represented by:
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. Jeffrey teaches the self-immolative linkers such as those shown above when conjugated to the core drug can result in surprising and unexpected benefits, including increased efficacy, decreased toxicity, and improvements in other pharmacokinetic characteristics (para [0289]).
Jeffrey doesn’t explicitly teach or suggest the elected camptothecin-linker compound.
Jeffrey 2 teaches camptothecin analogs for use in preparing conjugates, including antibody drug conjugates, which include the following (title & abstract; para [0003], [0046], [0049], [0067]; p. 253, para [0605], compound 2n):
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.
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.
It would have been prima facie obvious to one of ordinary skill in the art, before the effective filing date of the claims to have arrived at the elected camptothecin-linker compound, as shown, in consideration of the combined teachings of Jeffrey and Jeffrey 2:
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. Jeffrey teaches camptothecin conjugates composed of camptothecin derivatives conjugated via a linker to an antibody to be used to deliver the cytotoxic agent, camptothecin or derivative thereof, to a tumor cell. Jeffrey further teaches it is desirable to synthesize the camptothecin-linker compound prior to conjugation to an antibody, and provides an exemplary camptothecin-linker compound which has the same linker conjugated to a camptothecin derivative at the same point of attachment as for the elected species. Although Jeffrey doesn’t explicitly teach or suggest the same camptothecin derivative core as the elected species, Jeffrey 2 teaches this camptothecin core for conjugation to a linker. As such, one of ordinary skill in the art would have found it prima facie obvious to have replaced the camptothecin core of exemplary compound 116 as taught by Jeffrey with a different camptothecin core for attachment as exemplified by Jeffrey 2:
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. Additionally, as Jeffrey exemplifies a point of attachment of the camptothecin core to the linker as the -CH2-NH2 functional group, it would have been prima facie obvious to have attached the same linker at the same attachment point of the above shown camptothecin core as taught by Jeffrey 2. One of ordinary skill in the art would have been motivated to have done so given that different camptothecin derivatives are taught to be applicable for attachment to linkers, ultimately for further conjugation to an antibody, and have had a reasonable expectation of success.
Information Disclosure Statement
The IDS filed on 4/1/24 has been considered. However, numerous references cited on the IDS were not considered, as copies of the references were not submitted for consideration; these references are lined-through on the considered IDS.
Correspondence
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH PIHONAK whose telephone number is (571)270-7710. The examiner can normally be reached Monday-Friday 9:00-5:30 EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Kortney Klinkel can be reached at 571-270-5239. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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SARAH . PIHONAK
Primary Examiner
Art Unit 1627
/SARAH PIHONAK/Primary Examiner, Art Unit 1627
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