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 .
Claim Status
Claims 1-4, 6-11, and 14-20 are pending. Claims 5, 12, and 13 were canceled, and claims 1-3, 7-9, 14, and 17 were amended in the Reply to the Election Requirement filed 7/29/2026 relative to the claim set filed September 17, 2024, wherein such claims were not the originally filed claims filed February 12, 2024. Claims 4 and 18 are withdrawn. Claims 1-3, 6-11, 14-17, and 19-20 are presently considered.
Election/Restrictions
Applicant's election with traverse of the single, disclosed species of Example 6 in the Specification filed 2/12/2024 at page 49 at line 16 to page 50 at line 24 (i.e., an in vivo method for combining RLI-15 with trastuzumab emtansine) in the reply filed on 7/29/2026 is acknowledged. The traversal is on the ground(s) that the amended claim scope as filed 7/29/2026, after the requirement, now obviates the basis of the lack of unity determination set forth in the original requirement by allegedly forming a shared, special technical feature at amended claim 1 (see, e.g., Reply filed 7/29/2026 at 10-13). This is not found persuasive because the amended claim scope continues to lack a common special, technical feature as explained in the instant action, wherein the compounds and claimed method steps at instant claim 1 continue to unambiguously recite an inventive step for reasons set forth below under 35 USC 103, which is incorporated into the instant traversal.
The requirement is still deemed proper and is therefore made FINAL.
Examiner notes that Applicant mistakenly refers to multiple species as species elections (see, e.g., Reply filed 7/29/2026 at 8-9, referring to “first election”, “second election”, etc.). The requirement mailed 6/01/2026 required election of a single, disclosed species, and identification of parameters that define the single, disclosed species (see Requirement at page 4 at line 1, and footnote at page 4). Accordingly, for clarification, a single, elected species was required, elected, and it is understood to be the species disclosed at Example 6 in the Specification filed 2/12/2024 at page 49 at line 16 to page 50 at line 24 (i.e., an in vivo method for combining RLI-15 with trastuzumab emtansine).
The originally elected species is understood as follows: The single, elected species is understood to be a species disclosed at Example 6 in the Specification filed 2/12/2024 at page 49 at line 16 to page 50 at line 24 (i.e., an in vivo method for combining RLI-15 with trastuzumab emtansine). Regarding the patient population: The “cancer in a patient” is orthotopic huHER2/EMT-6 breast cancer in mice (see, e.g., Spec. filed 2/12/2024 at 49 at line 16 to page 50 at line 24), wherein such patients and method steps have been reasonably identified as an obvious variant of treatment for HER2-positive breast cancer in humans (see, e.g., Reply filed 7/29/2026 at 8-9). Regarding the IL-2/IL-15Rβγ agonist, the IL-2/IL-15Rβγ agonist is understood to be “RLI2” and also known as “SO-C101” or “CYT101”, and is known to be the “subject of the clinical trial NCT04234113” (see, e.g., Reply filed 7/29/2026 at 8-9; see also Spec. filed 2/12/2024 at 32 at lines 17-21). “RLI2”, “SO-C101”, or “SOT101” are identified as referring to an IL-15Rα-linker-IL-15 fusion protein “represented by SEQ ID NO: 9” (see, e.g., Reply filed 7/29/2026 at 8-9; see also Spec. filed 2/12/2024 at 13 at lines 29-32), wherein SEQ ID NO: 9 is
ITCPPPMSVEHADIWVKSYSLYSRERYICNSGFKRKAGTSSLTECVLNKATNVAHWTTPSLKCIRDPALVHQRPAPPSGGSGGGGSGGGSGGGGSGGNWVNVISDLKKIEDLIQSMHIDATLYTESDVHPSCKVTAMKCFLLELQVISLESGDASIHDTVENLIILANNSLSSNGNVTESGCKECEELEEKNIKEFLQSFVHIVQMFINTS
Accordingly, instant SEQ ID NO: 9 consists of an IL-15Rα (i.e., instant SEQ ID NO: 7), conjugated to an IL-15 (i.e., instant SEQ ID NO: 4), via a linker (i.e., instant SEQ ID NO: 8, underlined above). “RLI2” is identified as corresponding to CAS Registry No. 1416390-27-6, which is attached in the search notes of the instant action, and identifies that RLI2 is also known as “Nanrilkefusp alfa” and as SEQ ID NO: 16 of WO2015018529 and SEQ ID NO: 17 of WO2012175222. Regarding the IL-2/IL-15Rβγ agonist dosage and dosing frequency, the IL-2/IL-15Rβγ agonist is administered in four doses, on days 15-18, at 1 mg/kg subcutaneously (see, e.g., Spec. filed 2/12/2024 at 50 at lines 9-20, Figures 8(b)-8(c)). Regarding the cytotoxic compound capable of inducing immunogenic cell death (ICD)”, the cytotoxic compound is identified as trastuzumab emtansine (corresponding to KADCYLA®), which is CAS Registry Number 1018448-65-1 (see attached search notes, identifying alternative names of Ado-trastuzumab emtansine, PRO 132365, RG 3502, T-DM 1, and Trastuzumab-MCC-DM 1) (see, e.g., Reply filed 7/29/2026 at 8-9; see also Spec. filed 2/12/2024 at 20 at lines 10-15). Regarding the cytotoxic compound dosage and dosing frequency, at Example 6, trastuzumab emtansine is administered twice, on days 0 and 7, at 15 mg/kg intravenously (see, e.g., Reply filed 7/29/2026 at 8-9; see also Spec. filed 2/12/2024 at 49 at line 16 to page 50 at line 24), but the reply identifies that the election covers “human patients” and identifies that “human dosing regimens are described on page 38, lines 15 to 35” (see, e.g., Reply filed 7/29/2026 at 8-9), and these dosing regimens are understood to be obvious variants of the claimed species, and include administration of trastuzumab emtansine at 3.6 mg/kg by i.v. on Day 1(see also Spec. filed 2/12/2024 at 38 at lines 15 to 35), wherein SO-C101 is administered at 12 µg/kg subcutaneously on Days 8-9 and 15-16, or on Days 15-16, or on Days 15-16 and 22-23 (see id). Accordingly, these alternative treatment dosages and frequencies are understood to be obvious variants of the originally elected species. Regarding claims reading upon the originally elected species, the single, disclosed and elected species is identified as reading upon instant claims 1-3, 6-11, 14-17, and 19-20.
Following extensive search and examination, the originally elected species has been deemed anticipated and/or obvious in view of the prior art as applied below. Per MPEP § 803.02(III)(A),
Following election, the Markush claim will be examined fully with respect to the elected species and further to the extent necessary to determine patentability. Note that where a claim reads on multiple species, only one species needs to be taught or suggested by the prior art in order for the claim to be anticipated or rendered obvious...
If the Markush claim is not allowable, the provisional election will be given effect and examination will be limited to the Markush claim and claims to the elected species, with claims drawn to species patentably distinct from the elected species held withdrawn from further consideration.
Accordingly, claims 1-3, 6-11, 14-17, and 19-20 are rejected in view of the originally elected species and claims that do not read upon the originally elected species are withdrawn.
Claims 4 and 18 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. Applicant timely traversed the restriction (election) requirement in the reply filed on 7/29/2026.
Claims 1-3, 6-11, 14-17, and 19-20 are presently considered.
Priority
The priority claim to EP21191347.0 (filed 8/13/2021) and PCT/EP2022/072845 (filed 08/16/2022) are each acknowledged.
Information Disclosure Statement
The IDS filed 4/27/2026, 11/12/2025, and 2/12/2024 are acknowledged and presently considered.
Applicant should note that one or more documents disclosed on the IDS form submitted on 2/12/2024 were not considered because the copies provided were not fully legible (e.g., NPL cites 1-2 and 4).
Applicant should note that one or more documents disclosed on the IDS form submitted on 4/27/2026 and 2/12/2024 were not considered since they did not conform to 37 CFR 1.98(b) by providing a proper date, as 37 CFR 1.98(b) requires that each publication must be identified by publisher, author (if any), title, relevant pages of the publication, and date and place of publication. The date of publication supplied must include at least the month and year of publication, except that the year of publication (without the month) will be accepted if the applicant points out in the information disclosure statement that the year of publication is sufficiently earlier than the effective U.S. filing date and any foreign priority date so that the particular month of publication is not in issue. See MPEP 609.04(a). Here, the earliest priority claim is to EP21191347.0, filed 8/13/2021; therefore, all documents published in 2020 or later must be accompanied by both month and date of publication.
References that were not considered have been indicated by strike-though on the attached IDS forms. Although not considered, these documents have been placed in the application file, but the information referred to therein has not been considered as to the merits. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
Claim Interpretation
For purposes of examination, the claim scope has been interpreted as set forth below per the guidance set forth at MPEP § 2111. If Applicant disputes any interpretation, Applicant is invited to unambiguously identify any alleged misinterpretations or specialized definitions in the subsequent response to the instant action. Applicant is advised that a specialized definition should be properly supported and specifically identified (see, e.g., MPEP § 2111.01(IV), describing how Applicant may act as their own lexicographer).
Claim 1 is representative of the pending claim scope. Applicable claim interpretation is discussed below and under 35 USC 112(b).
“Comprising” is an open-ended transitional term (see, e.g., MPEP § 2111.03(I)), wherein additional steps or components are not excluded. However, “‘[c]omprising’ is a term of art used in claim language which means that the named elements are essential” (see, e.g., id.; see also Genentech, Inc. v. Chiron Corp., 112 F.3d 495, 501, 42 USPQ2d 1608, 1613 (Fed. Cir. 1997)).
Additional claim interpretations are set forth below.
Drawings
The drawings are objected to because Figures 2B(i)-(ii), 2C, 3A-3B, 4(i)-(4ii), 6A, 6(B)(i), 7A-7C, 8B, and 8C(ii) each recites “Kadcyla”. However, KADCYLA® is a trade name or a mark used in commerce (Serial No. 77962556). The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
The use of the term KADCYLA®, which is a trade name or a mark used in commerce (Serial No. 77962556), has been noted in this application, and appears to be pervasive and present throughout the lengthy specificaiton. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The lengthy specification has not been checked to the extent necessary to determine the presence of all possible minor errors. Applicant’s cooperation is requested in correcting any errors of which applicant may become aware in the specification.
Appropriate correction is required.
Claim Objections
Claims 14-15 are objected to because of the following informalities:
Claim 14 is objected to because it contains redundant and superfluous language that fails to meaningfully limit the pending claim scope. Specifically, claim 14 unnecessarily repeats substantial material found in claim 1 using slightly different phrasing, which is confusing and raises concerns regarding whether or not a difference in meaning is intended (see, e.g., Nystrom v. TREX Co., Inc., 424 F. 3d 1136, 1143 (Fed. Cir. 2005), explaining that "When different words or phrases are used in separate claims, a difference in meaning is presumed"). Redundant and superfluous language should be removed to enhance claim clarity and to minimize potential confusion. Examiner suggests the following amendments:
14. (Currently Amended) The method of claim 1, wherein theIL-15[[)]]/IL-15Rα[[)]] complexcomprises a flexible linker .
Claim 15 is objected to because it contains redundant and superfluous language that fails to meaningfully limit the pending claim scope. Specifically, claim 14 unnecessarily repeats substantial material found in claim 1. Redundant and superfluous language should be removed to enhance claim clarity and to minimize potential confusion. Examiner suggests the following amendments:
15. (Previously Presented) The method of claim 1, , wherein the IK-15/IL-15Rα complex comprises SEQ ID NO: 9.
Appropriate correction is required.
Claim Rejections
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.
Claims 1-3, 6-11, 14-17, and 19-20 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.
Amended claim 1 presently recites the indefinite “wherein” clause:
…wherein the IL-2/IL-l5Rβγ agonist is an interleukin 15 (IL-15)/interleukin-l5 receptor alpha (IL-l5Rα) complex comprising IL-15 or a derivative thereof with at least 92% sequence identity with SEO ID NO:4 and the sushi domain of IL-15Rα or a derivative thereof with at least 92% sequence identity with SEO ID NO: 6 or SEO ID NO: 7….
The usage of repeated conjugations (“or”, “and”, “or”, “or”) render the specific limitations defining the specific agonist being used indefinite because it is unclear what phrases modify which noun or phrase as presently written. More specifically, the agonist “complex” may be read as a “complex” defined by (I), (II), (III), or (IV), wherein such designations may change depending upon how the sentence is read:
…complex comprising (I) IL-15 or (II) a derivative thereof [of IL-15] with at least 92% sequence identity with SEO ID NO:4 and the sushi domain of IL-15Rα or a derivative thereof with at least 92% sequence identity with SEO ID NO: 6 or SEO ID NO: 7….
…complex comprising (I) IL-15 or (II) a derivative thereof [of IL-15] with at least 92% sequence identity with SEO ID NO:4 and the sushi domain of IL-15Rα or (III) a derivative thereof [of IL-15] with at least 92% sequence identity with SEO ID NO: 6 or SEO ID NO: 7….
…complex comprising (I) IL-15 or (II) a derivative thereof [of IL-15] with at least 92% sequence identity with SEO ID NO:4 and the sushi domain of IL-15Rα or (III) a derivative thereof [of IL-15] with at least 92% sequence identity with SEO ID NO: 6 or (IV) SEO ID NO: 7….
…complex comprising (I) IL-15 or (II) a derivative thereof [of IL-15] with at least 92% sequence identity with SEO ID NO:4 and the sushi domain of IL-15Rα or (III) a derivative thereof [of the sushi domain of IL-15Rα] with at least 92% sequence identity with SEO ID NO: 6 or SEO ID NO: 7….
…complex comprising (I) IL-15 or (II) a derivative thereof [of IL-15] with at least 92% sequence identity with SEO ID NO:4 and the sushi domain of IL-15Rα or (III) a derivative thereof with at least 92% sequence identity with SEO ID NO: 6 or (IV) SEO ID NO: 7….
…complex comprising (I) IL-15 or a derivative thereof [of IL-15] with at least 92% sequence identity with SEO ID NO:4 and (II) the sushi domain of IL-15Rα or a derivative thereof [the sushi domain of IL-15Rα] with at least 92% sequence identity with SEO ID NO: 6 or SEO ID NO: 7….
These different readings and interpretations are not exhaustive. Notably, the courts have stated that
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
Here, the claim claims to clearly and unambiguously define what exact structures do or do not define a “IL-15/IL-15Rα complex” within the scope of the Applicant’s claims, and the ambiguous language permits arbitrary interpretations to alter the scope and meaning of the instant claims. For purposes of examination in view of the prior art, the indefinite language is deemed satisfied by instant SEQ ID NO: 9, as present in the originally elected species. Clarification is required.
Amended claim 1 recites the “wherein” clause
…wherein the cytotoxic compound capable of inducing ICD is selected from the group consisting of an anthracycline; a microtubule-destabilizing agent including a vinca alkaloid, a taxane, an epothilone, eribulin, an auristatin, and maytansine or a maytansinoid, and tubulysine; bleomycin; a proteasomal inhibitor including bortezomib; an alkylating agent including cyclophosphamide, a platinum complex including oxaliplatin, and a pyrrolo-benzodiazepine, calicheamicin derivatives and topoisomerase I inhibitors, and a nucleoside analogue.
The “wherein” clause renders the claim scope indefinite in view of usage of semicolons coupled with the usage of both “and” and “including”; the clause suggests nested Markush Groupings within a larger Markush Grouping. If the larger Markush is presumably designated by the semicolons, then the claim encompasses five alternative groups:
an anthracycline;
a microtubule-destabilizing agent including a vinca alkaloid, a taxane, an epothilone, eribulin, an auristatin, and maytansine or a maytansinoid, and tubulysine;
bleomycin;
a proteasomal inhibitor including bortezomib;
an alkylating agent including cyclophosphamide, a platinum complex including oxaliplatin, and a pyrrolo-benzodiazepine, calicheamicin derivatives and topoisomerase I inhibitors, and a nucleoside analogue.
However, this renders the smaller Markush Groupings indefinite due to the usage of “and”, “or” and “including”. For example, it is unclear how many subgenera of microtubule-destabilizing agents are included in the claim scope or not; specifically, it is unclear if
a microtubule-destabilizing agent including a vinca alkaloid, a taxane, an epothilone, eribulin, an auristatin, and maytansine or a maytansinoid, and tubulysine;
should be read and interpreted as two combinations of multiple agents:
(i) a microtubule-destabilizing agent including [all] a vinca alkaloid, a taxane, an epothilone, eribulin, an auristatin, and maytansine; or (ii) a microtubule-destabilizing agent including [both] a maytansinoid and tubulysine.
Or read and interpreted as multiple agents defined by a single component:
(i) a microtubule-destabilizing agent including a vinca alkaloid, (ii) a microtubule-destabilizing agent including a taxane, (iii) a microtubule-destabilizing agent including an epothilone, (iv) a microtubule-destabilizing agent including an eribulin, (v) a microtubule-destabilizing agent including an auristatin, (vi) a microtubule-destabilizing agent including a maytansine or a maytansinoid; and (vii) a microtubule-destabilizing agent including a tubulysine.
Or as a single complex combination of all enumerated agents:
(i) a microtubule-destabilizing agent including [each of the following:] a vinca alkaloid, a taxane, an epothilone, eribulin, an auristatin, maytansine, and tubulysine; (ii) a microtubule-destabilizing agent including [each of the following:] a vinca alkaloid, a taxane, an epothilone, eribulin, an auristatin, maytansinoid, and tubulysine;
These are not intended to be exhaustive examples, but rather intended only to exemplify the indefiniteness of the claim scope as presently drafted. Similar issues exist with the “alkylating agent”, because it is unclear if
an alkylating agent including cyclophosphamide, a platinum complex including oxaliplatin, and a pyrrolo-benzodiazepine, calicheamicin derivatives and topoisomerase I inhibitors, and a nucleoside analogue.
should be read an interpreted as a three combinations defining a complex of alkylating agents:
(A) an alkylating agent including (i) cyclophosphamide, (ii) a platinum complex including oxaliplatin, and (B) an alkylating agent including (i) a pyrrolo-benzodiazepine, (ii) calicheamicin derivatives and (iii) topoisomerase I inhibitors, and (C) an alkylating agent including nucleoside analogue.
Or read and interpreted as multiple agents defined by a single component:
(i) an alkylating agent including cyclophosphamide, (ii) an alkylating agent including a platinum complex including oxaliplatin, (iii) an alkylating agent including a pyrrolo-benzodiazepine, (iv) an alkylating agent including calicheamicin derivatives, (v) an alkylating agent including topoisomerase I inhibitors, and (vi) an alkylating agent including a nucleoside analogue.
Or read and interpreted as a combination of single and multiple-component agents:
(i) an alkylating agent including cyclophosphamide, a platinum complex including oxaliplatin, and (ii) an alkylating agent including a pyrrolo-benzodiazepine, calicheamicin derivatives and topoisomerase I inhibitors, and (iii) an alkylating agent including a nucleoside analogue.
These are not intended to be exhaustive examples, but rather intended only to exemplify the indefiniteness of the claim scope as presently drafted. In sum, the current draft of claim 1 is rendered indefinite by the “wherein” clause identifying the cytotoxic compounds presently claimed, such that it is unclear what the metes and bounds of the pending claim scope may be due to the confusing usage of semicolons, commas, “and”, and “or” within the “wherein” clause. For purposes of examination in view of the prior art, the indefinite language is deemed satisfied by the cytotoxic compound of trastuzumab emtansine (corresponding to CAS Registry Number 1018448-65-1, and also known as Ado-trastuzumab emtansine, PRO 132365, RG 3502, T-DM 1, and Trastuzumab-MCC-DM 1) (see, e.g., Reply filed 7/29/2026 at 8-9; see also Spec. filed 2/12/2024 at 20 at lines 10-15). Clarification is required.
Claims 1 and 7 recite “calicheamicin derivatives”, but it is unclear what the metes and bounds of derivatization of calicheamicin includes and excludes as used in the present claims because, rather than providing a clear description of what structural motifs define such a “derivative” within the scope of the instant claims, the instant Specification instead recites and states that “calicheamicin derivatives are described in WO 2019/110725” (see, e.g., Spec. filed 2/12/2024 at page 23 at lines 15-20). This raises a substantial concern because WO’7251 pertains to enediyne compounds, which includes calicheamicins (CAL), esperamicins (ESP), dynemicin (DYN), namenamicin, shishijimicin, uncialamycin (UCM) (see, e.g., WO’725 at ¶[0002]), antibody-conjugated calicheamicins (see, e.g., WO’725 at ¶¶[0004]-[0006]), and other compounds. It is therefore unclear what the instant inventor is attempting to define and describe as “derivatives”, because, for example, if the description is only “derivatives comprising the calicheamicin of LL-E33288” (see, e.g., Spec. filed 2/12/2024 at page 23 at lines 15-20), then the phrase encompasses antibody conjugates, N-terminal modifications, etc. of LL-E33288. However, if the instant inventor is attempting to define “derivatives” as including all compounds “described in WO 2019/110725” 2 (see, e.g., Spec. filed 2/12/2024 at page 23 at lines 15-20), then this would potentially more broadly encompass calicheamicins (CAL), esperamicins (ESP), dynemicin (DYN), namenamicin, shishijimicin, uncialamycin (UCM), and antibody conjugates thereof (see, e.g., WO’725 at ¶[0002]). Accordingly, the meaning of “derivative” impacts the interpretation of the pending claim scope. Where applicant acts as his or her own lexicographer to specifically define a term of a claim contrary to its ordinary meaning, the written description must clearly redefine the claim term and set forth the uncommon definition so as to put one reasonably skilled in the art on notice that the applicant intended to so redefine that claim term. Process Control Corp. v. HydReclaim Corp., 190 F.3d 1350, 1357, 52 USPQ2d 1029, 1033 (Fed. Cir. 1999). Here, it is unclear if the term “calicheamicin derivatives” in claims 1 and 7 is used by the claim to mean “the calicheamicin of LL-E33288 and modified forms of LL-E33288 disclosed by WO’725,” or if the phrase “calicheamicin derivatives” in claims 1 and 7 is used to more broadly encompass all compounds “described in WO 2019/110725” 3 (see, e.g., Spec. filed 2/12/2024 at page 23 at lines 15-20), then this would more broadly encompass calicheamicins (CAL), esperamicins (ESP), dynemicin (DYN), namenamicin, shishijimicin, uncialamycin (UCM), and antibody conjugates thereof (see, e.g., WO’725 at ¶[0002]). Because it is unclear what the metes and bounds of the term may be, and because the specification does not clearly define or redefine the term, the claim scope is rendered indefinite because an artisan is left to arbitrarily guess at what specific compounds the instant inventor meant to include or exclude by such terminology.
Claim 1 recites functionally defined compounds that do not correspond to a particular structure/function relationship, and therefore such terms attempt to define a genus of unknown size and chemical structures by merely reciting the function the Applicant hopes and wishes to achieve, which renders the claim scope indefinite. More specifically, claim 1 recites “topoisomerase I inhibitors”, which presumably include a vast and highly varied genus including at least peptide nucleic acids, enzymes, nucleic acid aptamers, antibodies, small molecules, siRNAs, microRNAs, and other compounds of unknown structures capable of achieving such functionality. Per MPEP § 2173.05(g),
[T]he use of functional language in a claim may fail "to provide a clear-cut indication of the scope of the subject matter embraced by the claim" and thus be indefinite. In re Swinehart, 439 F.2d 210, 213 (CCPA 1971). For example, when claims merely recite a description of a problem to be solved or a function or result achieved by the invention, the boundaries of the claim scope may be unclear. . .
Here, the claims merely recite a description of functions or results to be achieved by the invention rather than a description of the structures capable of achieving the desired functions, and therefore the claims are indefinite per MPEP § 2173.05(g). This is reasonable because MPEP § 2173 identifies that the primary purpose of the requirement is to inform the public of the boundaries of what constitutes infringement of the patent, but here it is unclear what chemical compounds and structures do or do not infringe upon the scope of claim 1. Although it is reasonably assumed that the limitations of claim 1 may be fully satisfied by topotecan and exatecan, zero additional guidance or structure/function teachings are presented identifying any minimal functional motif defining chemical structures (e.g., peptides, nucleic acids, small molecules) capable of inhibiting topoisomerase I. Notably, the courts have stated that
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
Accordingly, because it is unclear what compounds do or do not satisfy the functional limitations of claim 1, and an artisan would be unable to identify infringing from non-infringing compounds, claim 1 is rejected as indefinite.
Claim 1 recites functionally defined compounds that do not correspond to a particular structure/function relationship, and therefore such terms attempt to define a genus of unknown size and chemical structures by merely reciting the function the Applicant hopes and wishes to achieve, which renders the claim scope indefinite. More specifically, claim 1 recites “a microtubule-destabilizing agent…”, which may presumably include a vast and highly varied genus including at least peptide nucleic acids, enzymes, nucleic acid aptamers, antibodies, small molecules, siRNAs, microRNAs, and other compounds of unknown structures capable of achieving such functionality. Per MPEP § 2173.05(g),
[T]he use of functional language in a claim may fail "to provide a clear-cut indication of the scope of the subject matter embraced by the claim" and thus be indefinite. In re Swinehart, 439 F.2d 210, 213 (CCPA 1971). For example, when claims merely recite a description of a problem to be solved or a function or result achieved by the invention, the boundaries of the claim scope may be unclear. . .
Here, the claims merely recite a description of functions or results to be achieved by the invention rather than a description of the structures capable of achieving the desired functions, and therefore the claims are indefinite per MPEP § 2173.05(g). This is reasonable because MPEP § 2173 identifies that the primary purpose of the requirement is to inform the public of the boundaries of what constitutes infringement of the patent, but here it is unclear what chemical compounds and structures do or do not infringe upon the scope of claim 1. Zero guidance or structure/function teachings are presented identifying any minimal functional motif defining chemical structures (e.g., peptides, nucleic acids, small molecules) capable of the required microtubule-destabilizing functionality. Notably, the courts have stated that
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
Accordingly, because it is unclear what compounds do or do not satisfy the functional limitations of claim 1, and an artisan would be unable to identify infringing from non-infringing compounds, claim 1 is rejected as indefinite.
Claims 1-3 and 6-7 refer to “a cytotoxic compound” that is “capable of inducing immunogenic cell death (ICD)”, which is a functional limitation that further limits the scope of enumerated cytotoxic compounds at claim 1, namely
…wherein the cytotoxic compound capable of inducing ICD is selected from the group consisting of an anthracycline; a microtubule-destabilizing agent including a vinca alkaloid, a taxane, an epothilone, eribulin, an auristatin, and maytansine or a maytansinoid, and tubulysine; bleomycin; a proteasomal inhibitor including bortezomib; an alkylating agent including cyclophosphamide, a platinum complex including oxaliplatin, and a pyrrolo-benzodiazepine, calicheamicin derivatives and topoisomerase I inhibitors, and a nucleoside analogue.
to a narrower subgenus of unknown size and chemical structures by merely reciting the function the Applicant hopes and wishes to achieve, which renders the claim scope indefinite. First, the enumerated list of “cytotoxic compounds capable of inducing ICD” at claim 1 (quoted above) is indefinite for reasons set forth in a preceding paragraph, and that discussion is incorporated herein. Second, even assuming arguendo that the enumerated species and subgenera at claim 1 were unambiguous and well known, that listing does not resolve the ambiguity of the functional limitation, because such language is presumed to further limit the enumerated species (i.e., the phrase “capable of inducing immunogenic cell death (ICD)” is a functional claim limitation further narrowing the scope of enumerated compounds to an unknown subgenus consisting of only those functionally “capable of inducing immunogenic cell death (ICD)”). Although it is reasonably understood that the subgenus of “cytotoxic compound[s] capable of inducing immunogenic cell death (ICD)” include at least those specific compounds enumerated at pages 39-41 of the specification (see, e.g., Spec. at 2/12/2024 at 39 at line 26 to page 41 at line 4, identifying the specific cytotoxic compounds of “Kadycyla”, “SOT102”, “gemtuzumab ozogamicin”, “brentuximab vedotin”, …..and “cyclophosphamide”, for about 22 total compounds), it is unclear what other compounds within the enumerated list are (or are not) “capable of inducing immunogenic cell death (ICD)” as instantly claimed, because the functional limitation does not actually correspond to a clear structure/function relationship on record. Accordingly, the claims merely recite a description of functions or results to be achieved by the invention rather than a description of the specific structures capable of achieving the desired functions, and therefore the claims are indefinite per MPEP § 2173.05(g). This is reasonable because MPEP § 2173 identifies that the primary purpose of the requirement is to inform the public of the boundaries of what constitutes infringement of the patent, but here it is unclear what specific chemical compounds and structures do or do not infringe upon the scope of claims 1-3 and 6-7, because zero additional guidance or structure/function teachings are presented identifying any minimal functional motif defining chemical structures (e.g., peptides, nucleic acids, small molecules) “capable of inducing immunogenic cell death (ICD)” commensurate in scope with the enumerated list at instant claim 1 . Notably, the courts have stated that
Regardless whether a compound is claimed per se or a method is claimed that entails the use of the compound, the inventor cannot lay claim to the subject matter unless he can provide a description of the compound sufficient to distinguish infringing compounds from non-infringing compounds, or infringing methods from non-infringing methods.” University of Rochester v. G.D. Searle Co., 69 USPQ2d 1886 1984 (CAFC 2004) (emphasis added).
Accordingly, because it is unclear what compounds do or do not satisfy the functional limitations of claim 1, and an artisan would be unable to identify infringing from non-infringing compounds, claims 1-3 and 6-7 are rejected as indefinite. For purposes of applying prior art, the claims are understood to encompass the specific species identified in the Specification (see, e.g., Spec. at 2/12/2024 at 39 at line 26 to page 41 at line 4). Examiner suggests amending claim 1 to remove the functional limitation “capable of inducing immunogenic cell death (ICD)” if such phrase is intended to be non-limiting (i.e., if all compounds in the enumerated list share this function, then reciting the function is unnecessary).
Claim 8 refers to “said calicheamicin”. There is insufficient antecedent basis for this limitation in the claim (see, e.g., Nystrom v. TREX Co., Inc., 424 F. 3d 1136, 1143 (Fed. Cir. 2005), explaining that "When different words or phrases are used in separate claims, a difference in meaning is presumed"). For purposes of applying prior art, it is reasonably presumed that the claim should read “said calicheamicin derivatives”.
Claim 11 recites the phrase “suffering from”, wherein “suffering” (i.e., the conscious emotions resulting from the endurance of physical, mental, or emotional pain, distress, or hardship) is commonly understood to be a relative term which therefore renders the claim indefinite. The term “suffering from” is not defined by the claim to clearly exclude relative interpretations, the specification does not provide a standard for ascertaining the requisite degree, and one of ordinary skill in the art would not be reasonably apprised of the scope of the invention. For purposes of applying prior art, the claim is interpreted as “the patient has a tumor expressing HER2”.
Claim 14 depends from amended claim 1, but appears to be broader in scope relative to instant claim 1, which raises material concerns regarding the difference in meaning between differences in language, because amended claim 1 recites
…wherein the IL-2/IL-l5Rβγ agonist is an interleukin 15 (IL-15)/interleukin-l5 receptor alpha (IL-l5Rα) complex comprising IL-15 or a derivative thereof with at least 92% sequence identity with SEO ID NO:4 and the sushi domain of IL-15Rα or a derivative thereof with at least 92% sequence identity with SEO ID NO: 6 or SEO ID NO: 7….
But claim 14 recites
…wherein the IL-2/IL-l5Rβγ agonist is an interleukin 15 (IL-15)/interleukin-l5 receptor alpha (IL-l5Rα) complex, wherein the complex is a fusion protein comprising the sushi domain of IL-15Rα or a derivative thereof, a flexible linker and the human IL-15 or a derivative thereof.
Accordingly, although amended claim 1 is ostensibly limited to “the sushi domain of IL-15Rα or a derivative thereof with at least 92% sequence identity with SEO ID NO: 6 or SEO ID NO: 7”, claim 14 more broadly encompasses any “sushi domain of IL-15Rα or a derivative thereof” (e.g., including derivatives presumably having less than 92% sequence identity). Likewise, claim 1 ostensibly limits the claim scope to “IL-15 or a derivative thereof with at least 92% sequence identity with SEO ID NO:4”, but claim 14 more broadly encompasses any “human IL-15 or a derivative thereof” (e.g., including derivates presumably having less than 92% identity with instant SEQ ID NO: 4). The usage of different words and phrases to describe the limitations at issue raise a material concern that the difference alters the pending claim scope, but it is unclear if claim 14 is intended to be broader than claim 1 or narrower in scope (see, e.g., Nystrom v. TREX Co., Inc., 424 F. 3d 1136, 1143 (Fed. Cir. 2005), explaining that "When different words or phrases are used in separate claims, a difference in meaning is presumed"). Accordingly, the claim is rejected as indefinite. For purposes of applying prior art, claim 14 is interpreted as lacking superfluous language of claim 14 already found in claim 1, and claim 14 is understood as equivalent to “The method of claim 1, wherein the IL-15/ IL-l5Rα complex comprises a flexible linker”. This is reasonable because the presence of a flexible linker appears to be the only unambiguous difference in scope between claims 1 and 14.
Claims 2-3, 6-11, 14-17, and 19-20 depend directly or indirectly from an indefinite base claim, and fail to clarify the indefiniteness of the base claim; accordingly, these claims are rejected as indefinite for the reasons applied above to the claims upon which they depend.
Claims 1-3, 6-11, 14-17, and 19-20 are rejected.
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.
[Prior Art Rejection 01]
Claims 1-3, 7-8, 14-15, 17, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over US10626155 (filed Jun. 22, 2012).
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The primary reference pertains to the usage of an “IL-15/ IL-l5Rα complex” comprising SEQ ID NO: 17 for treating cancer (see, e.g., US’155 at claims 1-8). Regarding instant claims 1, 14-15, 20, and an IL-15/ IL-l5Rα complex comprising instant SEQ ID NO: 9, the primary reference discloses instant SEQ ID NO: 9 as SEQ ID NO: 17 (compare instant SEQ ID NO: 9 with US’155 at SEQ ID NO: 17, showing 100% sequence identity). Therefore, the IL-15/ IL-l5Rα complex of the originally elected species is a prior art element. Regarding instant claim 1 and the combination of an IL-15/ IL-l5Rα complex comprising instant SEQ ID NO: 9 and also a “cytotoxic compound capable of inducing immunogenic cell death (ICD)”, US’155 discloses and directs artisans to “a method for treating cancer comprising the step of simultaneously, separately, or sequentially administering to a subject in need thereof a therapeutically effective amount of” an immunocytokine (e.g., SEQ ID NO: 17 of US’155) and a “therapeutic agent, preferably an anticancer agent” (see, e.g., US’155 at col. 3 at lines 25-45, col. 20 at line 35 to col. 21 at line 7), wherein the “therapeutic agent” is explicitly identified as including at least bleomycin, cyclophosphamide, cisplatin, oxaliplatin, doxorubicin, paclitaxel, vinblastine (i.e., a vinca alkaloid), and topotecan (i.e., an art-recognized topoisomerase I inhibitors) (see, e.g., US’155 at col. 19 at line 59 to col. 20 at line 17), wherein “subject” includes any mammals including rodents and humans (see, e.g., US’155 at col. 20 at lines 40-45). Furthermore, the antibody of trastuzumab is identified as capable of targeting HER2, and is identified as an “anticancer agent” that was approved for treatment of breast cancer circa 1998 (see, e.g., US’155 at col. 13 at lines 49-56, col. 14 at lines 1-3). Accordingly, methods of treating cancer by simultaneously, separately, or sequentially administering to a subject in need thereof a therapeutically effective amount of a therapeutic agent (e.g., bleomycin, cyclophosphamide, cisplatin, oxaliplatin, doxorubicin, paclitaxel, vinblastine, topotecan, trastuzumab, etc.) were already known, disclosed, and contemplated by the prior art. Regarding the elected species and the dosage utilized of SEQ ID NO: 17 of US’155, the primary reference teaches and directs artisans to utilize injections of 2.5 mg/kg, 1 mg/kg, 0.1 mg/kg or less of the immunocytokines of the invention (see, e.g., US’155 at col. 18 at lines 1-15). Regarding instant claims 1, 2, 3, and sequential administration of SEQ ID NO: 9 subsequent to administration of a “cytotoxic compound capable of inducing immunogenic cell death (ICD)”, US’155 discloses and directs artisans to “a method for treating cancer comprising the step of simultaneously, separately, or sequentially administering to a subject in need thereof a therapeutically effective amount of” an immunocytokine (e.g., SEQ ID NO: 17 of US’155) and a “therapeutic agent, preferably an anticancer agent” (see, e.g., US’155 at col. 3 at lines 25-45, col. 20 at line 35 to col. 21 at line 7). Accordingly, an artisan would readily appreciate and infer that “sequentially administering” two compounds could only be performed in two ways, namely SEQ ID NO: 17 could only be administered before or after the anticancer agent. Accordingly, such limitations do not weigh in favor of non-obviousness in view of the prior art. Regarding instant claims 7-8, and a “cytotoxic compound capable of inducing immunogenic cell death (ICD)” selected from, for example, doxorubicin or topotecan, the primary reference explicitly teaches and identifies that the “therapeutic agent” may be at least doxorubicin or topotecan (see, e.g., US’155 at col. 19 at line 59 to col. 20 at line 17). Accordingly, selection of a known compound for use in a known method does not weigh in favor of a determination of non-obviousness. Regarding claim 17 and subcutaneous or intraperitoneal administration of an IL-15/ IL-l5Rα complex comprising instant SEQ ID NO: 9, the described route of administration is not limited (see, e.g., US’155 at col. 3 at lines 25-45, col. 20 at line 35 to col. 21 at line 7), but “injection” is claimed and described (see, e.g., US’155 at claim 8, col. 18 at lines 1-25), which is reasonably inferred to include injections by intravenous and subcutaneous routes (see, e.g., US’155 at col. 18 at lines 1-25, noting that pharmaceutical compositions can be formulated for intravenous and subcutaneous administration routes). Regarding claim 19 and the treatment of a solid cancer, the primary reference is understood to cover method of treating any and all types of cancers (see, e.g., US’155 at col. 3 at lines 25-45, col. 20 at line 35 to col. 21 at line 7), which would necessarily include both solid and hematological cancers. In addition, the primary reference clearly identifies that “treating cancer” specifically means “regression of tumor growth, i.e., the decrease in size of a measurable tumor” (see, e.g., US’155 at col. 21 at lines 1-8), which would be understood to an artisan to pertain specifically to solid, measurable cancers.
The primary reference differs from the instant claims scope as follows: Although the primary reference directs artisans to “method[s] for treating cancer comprising the step of simultaneously, separately, or sequentially administering to a subject in need thereof a therapeutically effective amount of” SEQ ID NO: 17 and an anticancer agent (e.g., bleomycin, cyclophosphamide, cisplatin, oxaliplatin, doxorubicin, paclitaxel, vinblastine, topotecan, etc.), the primary reference does not actually reduce to practice or exemplify such methods in subjects.
Accordingly, the relevant issue is whether or not it would be obvious to perform a prior art method for treating cancer in a patient in need thereof, by administering, simultaneously or sequentially, a therapeutically effective amount of” SEQ ID NO: 17 and an anticancer agent (e.g., bleomycin, cyclophosphamide, cisplatin, oxaliplatin, doxorubicin, paclitaxel, vinblastine, topotecan, etc.), exactly as taught and suggested by the prior art, in order to predictably and desirably treat the cancer as explicitly taught by the primary reference. Here, because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), an artisan would be motivated to practice the full scope of the disclosed invention with a reasonable expectation of successfully treating cancer, exactly as taught and suggested by the primary reference.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed invention is the combination of prior art elements (i.e., SEQ ID NO: 17 of US’155, anticancer agents as taught by US’155) according to known methods for treating cancer as disclosed by the primary reference, wherein such combination would predictably yield a method for treating cancer comprising the step of sequentially administering to a subject in need thereof a therapeutically effective amount of SEQ ID NO: 17 of US’155 and an anticancer agent, wherein such treatment would predictably and desirably lead to the treatment of the cancer (see, e.g., MPEP § 2143(I)(A), (G)).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to practice known methods using known reagents to obtain the exact result taught and disclosed by the prior art.
Accordingly, claims 1-3, 7-8, 14-15, 17, and 19-20 are rejected.
[Prior Art Rejection 02]
Claims 6, 9-10, 11, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over US10626155 (filed Jun. 22, 2012) as applied to claims 1-3, 7-8, 14-15, 17, and 19-20 above, and further in view of US2012/0107302A1.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section and rejection(s) above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The teachings of the primary reference as applied to instant claims 1-3, 7-8, 14-15, 17, and 19-20, have been discussed above in a preceding rejection, and those teachings are incorporated herein. Regarding instant claim 16 and the aspect of instant SEQ ID NO: 9, the primary reference discloses instant SEQ ID NO: 9 as SEQ ID NO: 17 (compare instant SEQ ID NO: 9 with US’155 at SEQ ID NO: 17, showing 100% sequence identity). Therefore, as discussed in the preceding rejection in view of the primary reference, the IL-15/ IL-l5Rα complex of the originally elected species is a prior art element.
The primary reference differs from instant claims 6, 9-10, 11, and 16 as follows: Although the primary reference directs artisans to “method[s] for treating cancer comprising the step of simultaneously, separately, or sequentially administering to a subject in need thereof a therapeutically effective amount of” SEQ ID NO: 17 and an anticancer agent, the primary reference does not specifically teach that the “anticancer agent” may be (or include) trastuzumab emtansine in a method of treating HER-2 positive breast cancer.
Regarding instant claims 6, 9-10, 11, 16, and trastuzumab emtansine, “trastuzumab emtansine” is also known in the art as “Trastuzumab-MCC-DM 1”4, which is a prior art element, and art-recognized antibody-drug conjugate, wherein DM1 is a maytansinoid and Trastuzumab is a HER2-directed antibody (see, e.g., US’302 at ¶¶[0002], [0006], [0082]-[0085]), wherein trastuzumab-MCC-DM 1 is a “first-in-class HER2 antibody-drug conjugate (ADC)” used to treat patients “with HER2+ metastatic breast cancer” (see id.; see also id. at ¶[0068]), which may be utilized in combination therapies with other drugs (see, e.g., US’302 at ¶¶[0007]), and administered “separately in alternation (alternating, sequential dosages)” (see, e.g., US’302 at ¶¶[0016]-[0017], [0065]-[0066]). Regarding instant claim 11 and HER positive cancer, US’302 expressly identifies that trastuzumab-MCC-DM 1 is a “first-in-class HER2 antibody-drug conjugate (ADC)” used to treat patients “with HER2+ metastatic breast cancer” (see, e.g. ,US’302 at ¶¶[0002], [0006], [0068], [0082]-[0085]). Therefore, an artisan would readily appreciate that such compounds could be utilized to treat patients having HER2-positive breast cancers. Regarding the elected species and the dosage of trastuzumab-MCC-DM 1 utilized, US’302 exemplifies the usage of trastuzumab-MCC-DM 1 in phase I studies at 3.6 mg/kg by IV infusion once every 3 weeks (see, e.g., US’302 at ¶¶[0086]).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): First, the invention is understood to be the simple substitution of one art-recognized anticancer drug (i.e., trastuzumab-MCC-DM 1) in place of another in the known methods for treating cancer as disclosed by the primary reference, wherein such combination would predictably yield a method for treating cancer, and specifically HER-2 positive breast cancer, comprising the step of sequentially administering to a subject in need thereof a therapeutically effective amount of SEQ ID NO: 17 of US’155 and the anticancer agent of trastuzumab-MCC-DM 1, wherein such treatment would predictably and desirably lead to the treatment of the breast cancer, wherein each compound would merely be expected to perform its art-recognized function in combination, as it does separately (see, e.g., MPEP § 2143(I)(B), (G)). Second, or alternatively, both SEQ ID NO: 17 of US’155 and trastuzumab-MCC-DM 1 are separately taught in the art for use in combination therapies for the treatment of cancers, and per MPEP § 2144.06 "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980); accordingly, here it would be obvious to simply combine two prior art therapies for treating cancers, including breast cancer, in order to yield a combined therapy for the very same purpose, because the combination of such elements and methods flows logically from their having been individually taught in the prior art. Such a combination would be predicted and expected to treat cancer, such as breast cancers, exactly as taught and suggested by the prior art.
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to practice known methods using known reagents to obtain the exact result taught and disclosed by the prior art.
Claims 6, 9-10, 11, and 16 are rejected.
[Prior Art Rejection 03]
Claims 1-3, 6-11, 14-17, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over US10626155 (filed Jun. 22, 2012) in view of US2012/0107302A1 as applied to claims 1-3, 6-11, 14-17, and 19-20 above, and further in view of WO2020/234387 (Nov. 26, 2020; cited in IDS filed 11/12/2025 as cite No. 39).
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section and rejection(s) above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below. The instant rejection addresses unclaimed limitations present in the originally elected species.
The teachings of the primary and secondary references as applied to instant claims 1-3, 6-11, 14-17, and 19-20, have been discussed above in a preceding rejection, and those teachings are incorporated herein.
The primary reference in view of the secondary reference differs from the originally elected species as follows: Although the prior art suggests, renders obvious, and directs artisans to methods of treating cancer in human patients by administering compounds comprising SEQ ID NO: 9 and trastuzumab-MCC-DM 1 at overlapping dosages, the prior art does not direct artisans to “human dosing regimens are described on page 38, lines 15 to 35” (see, e.g., Reply filed 7/29/2026 at 8-9), such as administering trastuzumab emtansine on Day 1 (see also Spec. filed 2/12/2024 at 38 at lines 15 to 35), and SO-C101 (SEQ ID NO: 9) on Days 8-9 and 15-16, or on Days 15-16, or on Days 15-16 and 22-23 (see id). Therefore, the relevant issue is whether or not the dosing regimen and frequency of the originally elected species is sufficient to establish non-obviousness.
An artisan planning to practice the methods disclosed and suggested by the primary reference in view of the secondary reference would review available prior art pertinent to SEQ ID NO: 17 of WO’155 and pertinent to anticancer agents, such as trastuzumab-drug agents. Such review would direct artisans to WO2020/234387, which pertains to IL-2/IL-15Rβγ “pulsed” dosing regiments for the treatment of cancer (see, e.g., WO’387 at title, abs, claim 1, 34 at lines 4-21).
WO’387 pertains to related subject matter relative to the primary and secondary references. Specifically, WO’387 is directly pertinent to the primary reference because SEQ ID NO: 17 of US’155 comprises “RLI2” (or “SO-C101”), which is identified by WO’387 as an IL-15/IL-15Rα complex (compare WO’387 at p. 12 at lines 19-25, p. 48 at line 45 to p. 49 at line 5, claims 35, SEQ ID NO: 9 with US’155 at SEQ ID NO: 17, showing 100% sequence identity), and therefore, an artisan would readily appreciate that the guidance pertaining to treatment of cancers using IL-15/IL-15Rα complex comprising SEQ ID NO: 9 of WO’387 were relevant to the structure and methods of US’155.
Regarding the “pulsed” dosing regimen of the originally elected species, WO’387 teaches and claims methods of treating cancer, including breast cancer (see WO’387 at 27 at lines 16-20, 62 at lines 14-23), by administering to a human patient an IL-2/IL-15Rβγ agonist at 0.1 µg/kg to 50 ug/kg, such as 12µg/kg (see, e.g., WO’387 at claims 1, 4-5), wherein administration is by s.c. or i.p. injection (see, e.g., WO’387 at claims 13 and 17), wherein the IL-2/IL-15Rβγ agonist is an IL-15/IL-15Rα complex and specifically SEQ ID NO: 9 (see, e.g., WO’387 at claim 21; compare id. with instant SEQ ID NO: 9, showing 100% identity), wherein the IL-2/IL-15Rβγ agonist is administered in combination with another therapeutic agent that may be a therapeutic anti-HER2 antibody (see WO’387 at 33 at lines 15-17, noting this includes including trastuzumab and conjugates thereof) which may be administered on the same or different days including the “beginning of the first period” of each cycle (see, e.g., WO’387 at claims 22-26 and 29), wherein the IL-2/IL-15Rβγ agonist may be administered on 2-4 consecutive days of each 5-9 day cyclical administration period, wherein administration periods may be separated by 5-20 days (see, e.g., WO’387 at claims 1 on p. 77). Accordingly, the guidance of WO’387 is understood to apply to the methods of US’155 and to anticancer agents such as therapeutic anti-HER2 antibody (e.g., trastuzumab and conjugates thereof as taught by the secondary reference).
Accordingly, an artisan reviewing relevant methods of practicing the methods of treating cancer as taught and suggested by the primary and secondary references would readily appreciate that compounds comprising SEQ ID NO: 9 of WO’387 could be administered in a “pulsed” dosing regimen, at known dosages, in combination with known therapeutic anti-HER2 antibodies, wherein compounds comprising SEQ ID NO: 9 of WO’387 would be administered by s.c. or i.p. at 0.1 µg/kg to 50 ug/kg on 2-4 consecutive days of each 5-9 day cyclical administration period, wherein administration periods may be separated by 5-20 days (see, e.g., WO’387 at claims 1, 4-5, 13, 17, 21-26, 29), wherein a second therapeutic anti-HER2 antibodies could be administered on the same or different days including the “beginning of the first period” of each cycle (see, e.g., WO’387 at claims 22-26 and 29). Critically, such “pulsed” administration fully encompasses and overlaps in scope with the claimed “pulsed” administration timing present in the originally elected species (see, e.g., MPEP § 2144.05(I), noting that “where the claimed ranges ‘overlap or lie inside ranges disclosed by the prior art’ a prima facie case of obviousness exists”).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): It has long been settled to be no more than routine experimentation for one of ordinary skill in the art to discover an optimum value of a result effective variable. "[W]here the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum of workable ranges by routine experimentation." Application of Aller, 220 F.2d 454, 456, 105 USPQ 233, 235-236 (C.C.P.A. 1955). "No invention is involved in discovering optimum ranges of a process by routine experimentation." Id. at 458, 105 USPQ at 236-237. The "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Application of Boesch, 617 F.2d 272, 276, 205 USPQ 215, 218-219 (C.C.P.A. 1980). Since Applicant has not disclosed that the specific days of administration limitations recited in the elected species are for any particular purpose or solve any stated problem and the prior art teaches that pulsed administration routinely involves consecutive days of administration separated by days of no treatment, wherein the exact amounts may vary within known ranges, and all such parameters appear to work equally as well, absent unexpected results commensurate in scope with the requirements of MPEP § 716.02, it would have been obvious for one of ordinary skill to discover the optimum workable ranges of the methods disclosed by the prior art by normal optimization procedures known in the pulsed administration treatment arts.
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to practice known methods using known reagents to obtain the exact result taught and disclosed by the prior art.
Claims 1-3, 6-11, 14-17, and 19-20 are rejected.
[Prior Art Rejection 04]
Claims 1-3, 6-11, 14-17, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over US10899816 (published Jan. 26, 2021; priority to Jun. 22, 2012; corresponding to US2018/0312560A1 published Nov. 1, 2018).
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The primary reference pertains to the usage of an “IL-15/ IL-l5Rα complex” comprising SEQ ID NO: 17 for treating cancer (see, e.g., US’816 at claims 1-5). Regarding instant claims 1, 14-15, 20, and an IL-15/ IL-l5Rα complex comprising instant SEQ ID NO: 9, the primary reference discloses instant SEQ ID NO: 9 as SEQ ID NO: 17 (compare instant SEQ ID NO: 9 with US’816 at SEQ ID NO: 17, showing 100% sequence identity). Therefore, the IL-15/ IL-l5Rα complex of the originally elected species is a prior art element. Regarding instant claim 1 and the combination of an IL-15/ IL-l5Rα complex comprising instant SEQ ID NO: 9 and also a “cytotoxic compound capable of inducing immunogenic cell death (ICD)”, US’816 discloses and directs artisans to “a method for treating cancer comprising the step of simultaneously, separately, or sequentially administering to a subject in need thereof a therapeutically effective amount of” an immunocytokine (e.g., SEQ ID NO: 17 of US’816) and a “therapeutic agent, preferably an anticancer agent” (see, e.g., US’816 at col. 3 at lines 25-45, col. 20 at line 35 to col. 21 at line 7), wherein the “therapeutic agent” is explicitly identified as including at least bleomycin, cyclophosphamide, cisplatin, oxaliplatin, doxorubicin, paclitaxel, vinblastine (i.e., a vinca alkaloid), and topotecan (i.e., an art-recognized topoisomerase I inhibitors) (see, e.g., US’816 at col. 19 at line 59 to col. 20 at line 17), wherein “subject” includes any mammals including rodents and humans (see, e.g., US’816 at col. 20 at lines 40-45). Furthermore, the antibody of trastuzumab is identified as capable of targeting HER2, and is identified as an “anticancer agent” that was approved for treatment of breast cancer circa 1998 (see, e.g., US’816 at col. 13 at lines 49-56, col. 14 at lines 1-3). Accordingly, methods of treating cancer by simultaneously, separately, or sequentially administering to a subject in need thereof a therapeutically effective amount of a therapeutic agent (e.g., bleomycin, cyclophosphamide, cisplatin, oxaliplatin, doxorubicin, paclitaxel, vinblastine, topotecan, trastuzumab, etc.) were already known, disclosed, and contemplated by the prior art. Regarding the dosage utilized of SEQ ID NO: 17 of US’816, the primary reference teaches and directs artisans to utilize injections of 2.5 mg/kg or 1 mg/kg or less of the immunocytokines of the invention (see, e.g., US’816 at col. 18 at lines 1-15). Regarding instant claims 1, 2, 3, and sequential administration of SEQ ID NO: 9 subsequent to administration of a “cytotoxic compound capable of inducing immunogenic cell death (ICD)”, US’816 discloses and directs artisans to “a method for treating cancer comprising the step of simultaneously, separately, or sequentially administering to a subject in need thereof a therapeutically effective amount of” an immunocytokine (e.g., SEQ ID NO: 17 of US’816) and a “therapeutic agent, preferably an anticancer agent” (see, e.g., US’816 at col. 3 at lines 25-45, col. 20 at line 35 to col. 21 at line 7). Accordingly, an artisan would readily appreciate and infer that “sequentially administering” two compounds could only be performed in two ways, namely SEQ ID NO: 17 could only be administered before or after the anticancer agent. Accordingly, such limitations do not weigh in favor of non-obviousness in view of the prior art. Regarding instant claims 7-8, and a “cytotoxic compound capable of inducing immunogenic cell death (ICD)” selected from, for example, doxorubicin or topotecan, the primary reference explicitly teaches and identifies that the “therapeutic agent” may be at least doxorubicin or topotecan (see, e.g., US’816 at col. 19 at line 59 to col. 20 at line 17). Accordingly, selection of a known compound for use in a known method does not weigh in favor of a determination of non-obviousness. Regarding claim 17 and subcutaneous or intraperitoneal administration of an IL-15/ IL-l5Rα complex comprising instant SEQ ID NO: 9, the described route of administration is not limited (see, e.g., US’816 at col. 3 at lines 25-45, col. 20 at line 35 to col. 21 at line 7), but “injection” is claimed and described (see, e.g., US’816 at claim 8, col. 18 at lines 1-25), which is reasonably inferred to include injections by intravenous and subcutaneous routes (see, e.g., US’816 at col. 18 at lines 1-25, noting that pharmaceutical compositions can be formulated for intravenous and subcutaneous administration routes). Regarding claim 19 and the treatment of a solid cancer, the primary reference is understood to cover method of treating any and all types of cancers (see, e.g., US’816 at col. 3 at lines 25-45, col. 20 at line 35 to col. 21 at line 7), which would necessarily include both solid and hematological cancers. In addition, the primary reference clearly identifies that “treating cancer” specifically means “regression of tumor growth, i.e., the decrease in size of a measurable tumor” (see, e.g., US’816 at col. 21 at lines 1-8), which would be understood to an artisan to pertain specifically to solid, measurable cancers.
The primary reference differs from the instant claims scope as follows: Although the primary reference directs artisans to “method[s] for treating cancer comprising the step of simultaneously, separately, or sequentially administering to a subject in need thereof a therapeutically effective amount of” SEQ ID NO: 17 and an anticancer agent (e.g., bleomycin, cyclophosphamide, cisplatin, oxaliplatin, doxorubicin, paclitaxel, vinblastine, topotecan, etc.), the primary reference does not actually reduce to practice or exemplify such methods in subjects.
Accordingly, the relevant issue is whether or not it would be obvious to perform a prior art method for treating cancer in a patient in need thereof, by administering, simultaneously or sequentially, a therapeutically effective amount of” SEQ ID NO: 17 and an anticancer agent (e.g., bleomycin, cyclophosphamide, cisplatin, oxaliplatin, doxorubicin, paclitaxel, vinblastine, topotecan, etc.), exactly as taught and suggested by the prior art, in order to predictably and desirably treat the cancer as explicitly taught by the primary reference. Here, because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)), an artisan would be motivated to practice the full scope of the disclosed invention with a reasonable expectation of successfully treating cancer, exactly as taught and suggested by the primary reference.
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The claimed invention is the combination of prior art elements (i.e., SEQ ID NO: 17 of US’816, anticancer agents as taught by US’816) according to known methods for treating cancer as disclosed by the primary reference, wherein such combination would predictably yield a method for treating cancer comprising the step of sequentially administering to a subject in need thereof a therapeutically effective amount of SEQ ID NO: 17 of US’816 and an anticancer agent, wherein such treatment would predictably and desirably lead to the treatment of the cancer (see, e.g., MPEP § 2143(I)(A), (G)).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to practice known methods using known reagents to obtain the exact result taught and disclosed by the prior art.
Accordingly, claims 1-3, 7-8, 14-15, 17, and 19-20 are rejected.
[Prior Art Rejection 05]
Claims 6, 9-10, 11, and 16 are rejected under 35 U.S.C. 103 as being unpatentable over US10899816 (published Jan. 26, 2021; priority to Jun. 22, 2012) as applied to claims 1-3, 7-8, 14-15, 17, and 19-20 above, and further in view of US2012/0107302A1.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section and rejection(s) above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The teachings of the primary reference as applied to instant claims 1-3, 7-8, 14-15, 17, and 19-20, have been discussed above in a preceding rejection, and those teachings are incorporated herein. Regarding instant claim 16 and the aspect of instant SEQ ID NO: 9, the primary reference discloses instant SEQ ID NO: 9 as SEQ ID NO: 17 (compare instant SEQ ID NO: 9 with US’816 at SEQ ID NO: 17, showing 100% sequence identity). Therefore, as discussed in the preceding rejection in view of the primary reference, the IL-15/ IL-l5Rα complex of the originally elected species is a prior art element.
The primary reference differs from instant claims 6, 9-10, 11, and 16 as follows: Although the primary reference directs artisans to “method[s] for treating cancer comprising the step of simultaneously, separately, or sequentially administering to a subject in need thereof a therapeutically effective amount of” SEQ ID NO: 17 and an anticancer agent, the primary reference does not specifically teach that the “anticancer agent” may be (or include) trastuzumab emtansine in a method of treating HER-2 positive breast cancer.
Regarding instant claims 6, 9-10, 11, 16, and trastuzumab emtansine, “trastuzumab emtansine” is also known in the art as “Trastuzumab-MCC-DM 1”5, which is a prior art element, and art-recognized antibody-drug conjugate, wherein DM1 is a maytansinoid and Trastuzumab is a HER2-directed antibody (see, e.g., US’302 at ¶¶[0002], [0006], [0082]-[0085]), wherein trastuzumab-MCC-DM 1 is a “first-in-class HER2 antibody-drug conjugate (ADC)” used to treat patients “with HER2+ metastatic breast cancer” (see id.; see also id. at ¶[0068]), which may be utilized in combination therapies with other drugs (see, e.g., US’302 at ¶¶[0007]), and administered “separately in alternation (alternating, sequential dosages)” (see, e.g., US’302 at ¶¶[0016]-[0017], [0065]-[0066]). Regarding instant claim 11 and HER positive cancer, US’302 expressly identifies that trastuzumab-MCC-DM 1 is a “first-in-class HER2 antibody-drug conjugate (ADC)” used to treat patients “with HER2+ metastatic breast cancer” (see, e.g. ,US’302 at ¶¶[0002], [0006], [0068], [0082]-[0085]). Therefore, an artisan would readily appreciate that such compounds could be utilized to treat patients having HER2-positive breast cancers. Regarding the elected species and the dosage of trastuzumab-MCC-DM 1 utilized, US’302 exemplifies the usage of trastuzumab-MCC-DM 1 in phase I studies at 3.6 mg/kg by IV infusion once every 3 weeks (see, e.g., US’302 at ¶¶[0086]).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): First, the invention is understood to be the simple substitution of one art-recognized anticancer drug (i.e., trastuzumab-MCC-DM 1) in place of another in the known methods for treating cancer as disclosed by the primary reference, wherein such combination would predictably yield a method for treating cancer, and specifically HER-2 positive breast cancer, comprising the step of sequentially administering to a subject in need thereof a therapeutically effective amount of SEQ ID NO: 17 of US’816 and the anticancer agent of trastuzumab-MCC-DM 1, wherein such treatment would predictably and desirably lead to the treatment of the breast cancer, wherein each compound would merely be expected to perform its art-recognized function in combination, as it does separately (see, e.g., MPEP § 2143(I)(B), (G)). Second, or alternatively, both SEQ ID NO: 17 of US’816 and trastuzumab-MCC-DM 1 are separately taught in the art for use in combination therapies for the treatment of cancers, and per MPEP § 2144.06 "It is prima facie obvious to combine two compositions each of which is taught by the prior art to be useful for the same purpose, in order to form a third composition to be used for the very same purpose.... [T]he idea of combining them flows logically from their having been individually taught in the prior art." In re Kerkhoven, 626 F.2d 846, 850, 205 USPQ 1069, 1072 (CCPA 1980); accordingly, here it would be obvious to simply combine two prior art therapies for treating cancers, including breast cancer, in order to yield a combined therapy for the very same purpose, because the combination of such elements and methods flows logically from their having been individually taught in the prior art. Such a combination would be predicted and expected to treat cancer, such as breast cancers, exactly as taught and suggested by the prior art.
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to practice known methods using known reagents to obtain the exact result taught and disclosed by the prior art.
Claims 6, 9-10, 11, and 16 are rejected.
[Prior Art Rejection 06]
Claims 1-3, 6-11, 14-17, and 19-20 are rejected under 35 U.S.C. 103 as being unpatentable over WO2020/234387 (Nov. 26, 2020; cited in IDS filed 11/12/2025 as cite No. 39) and further in view of US2012/0107302A1.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
WO2020/234387, which pertains to IL-2/IL-15Rβγ “pulsed” dosing regiments for the treatment of cancer (see, e.g., WO’387 at title, abs, claim 1, 34 at lines 4-21). Regarding instant claims 1, 14-16, 20 and the structure of instant SEQ ID NO: 9, SEQ ID NO: 9 of WO’387 is understood to be identical to instant SEQ ID NO: 9 (compare WO’387 at p. 12 at lines 19-25, p. 48 at line 45 to p. 49 at line 5, claims 35, SEQ ID NO: 9 with instant SEQ ID NO: 9, showing 100% sequence identity). Accordingly, the specific structure of “RLI2” (or “SO-C101”) as claimed is an art-recognized IL-15/IL-15Rα complex (see, e.g., WO’387 at 12 at lines 19-25, p. 48 at line 45 to p. 49 at line 5, claims 35, SEQ ID NO: 9). Regarding claims 1, 19, and the treatment of solid or hematological cancers by administering an IL-15/IL-15Rα complex comprising instant SEQ ID NO: 9, WO’387 directs artisans to treat cancers, including breast cancers (see WO’387 at 27 at lines 16-20, 62 at lines 14-23), by administering to a human patient the IL-2/IL-15Rβγ agonist of SEQ ID NO: 9 at 0.1 µg/kg to 50 ug/kg, such as 12µg/kg (see, e.g., WO’387 at claims 1, 4-5, 21). Regarding instant claims 1-3, and the administration of the IL-15/IL-15Rα complex in combination with an additional therapeutic agent that may be administered simultaneously or sequentially, WO’387 identifies that such methods of treating cancer by administering SEQ ID NO: 9 in combination with another therapeutic agent were already known in the prior art (see, e.g., WO’387 at claims 22-26 and 29, at page 33 at lines 15-17), wherein the compounds may be administered on the same or different days (see, e.g., WO’387 at claims 22-26 and 29), wherein administration on different days necessitates sequential administration which can happen in only two orders. Regarding instant claim 17 and the subcutaneous (s.c.) or intraperitoneal (i.p.) administration of the IL-15/IL-15Rα complex,WO’387 directs artisans to treat cancers by administering to a human patient an IL-2/IL-15Rβγ agonist, such as SEQ ID NO: 9, at 0.1 µg/kg to 50 ug/kg, such as 12µg/kg (see, e.g., WO’387 at claims 1, 4-5, 21), wherein such agonist may be administered in combination with another therapeutic agent were already known in the prior art (see, e.g., WO’387 at claims 22-26 and 29, at page 33 at lines 15-17), and wherein administration is by s.c. or i.p. injection (see, e.g., WO’387 at claims 13 and 17).
The primary reference differs from the instant claims as follows: Although the primary reference directs artisans to methods for treating cancer comprising the step of sequentially administering to a subject in need thereof at 0.1 µg/kg to 50 ug/kg of instant SEQ ID NO: 9 via subcutaneous injection, in combination with another therapeutic agent, the primary reference does not specifically teach that the additional therapeutic agent is trastuzumab emtansine.
Although WO’387 does not expressly teach trastuzumab emtansine, WO’387 does identify and fairly inform artisans that the additional therapeutic agent may be a therapeutic anti-HER2 antibody (see WO’387 at claims 22-26 and 29, page 33 at lines 15-17, noting this includes including trastuzumab and conjugates thereof). Accordingly, an artisan would readily appreciate that such compounds could be predictably utilized to treat cancer within the scope of the WO’387 disclosure.
US2012/0107302A1 pertains to the treatment of cancers, including breast cancer by administering trastuzumab-MCC-DM 1. Regarding instant claims 1, 6, 9-10, 11, 16, and trastuzumab emtansine, “trastuzumab emtansine” is also known in the art as “Trastuzumab-MCC-DM 1”6, which is a prior art element, and art-recognized antibody-drug conjugate, wherein DM1 is a maytansinoid and Trastuzumab is a HER2-directed antibody (see, e.g., US’302 at ¶¶[0002], [0006], [0082]-[0085]), wherein trastuzumab-MCC-DM 1 is a “first-in-class HER2 antibody-drug conjugate (ADC)” used to treat patients “with HER2+ metastatic breast cancer” (see id.; see also id. at ¶[0068]), which may be utilized in combination therapies with other drugs (see, e.g., US’302 at ¶¶[0007]), and administered “separately in alternation (alternating, sequential dosages)” (see, e.g., US’302 at ¶¶[0016]-[0017], [0065]-[0066]). Regarding instant claim 11 and HER positive cancer, US’302 expressly identifies that trastuzumab-MCC-DM 1 is a “first-in-class HER2 antibody-drug conjugate (ADC)” used to treat patients “with HER2+ metastatic breast cancer” (see, e.g. ,US’302 at ¶¶[0002], [0006], [0068], [0082]-[0085]). Therefore, an artisan would readily appreciate that such compounds could be utilized to treat patients having HER2-positive breast cancers. Regarding the elected species and the dosage of trastuzumab-MCC-DM 1 utilized, US’302 exemplifies the usage of trastuzumab-MCC-DM 1 in phase I studies at 3.6 mg/kg by IV infusion once every 3 weeks (see, e.g., US’302 at ¶¶[0086]).
Therefore, it would have been obvious to one of ordinary skill in the art, either before the effective filing date of the claimed invention (AIA ) or otherwise at the time the invention was made (pre-AIA ), to arrive at the instantly claimed invention in view of the prior art for at least the following reason(s): The invention is understood to be the simple combination of prior art elements, or otherwise the simple substitution of one art-recognized therapeutic agent (i.e., trastuzumab-MCC-DM 1) in place of another, in the known methods for treating cancer as disclosed by the primary reference, wherein such combination would predictably yield a method for treating cancers, (e.g., HER2 positive breast cancer), comprising the step of sequentially (e.g., on different days) administering to a subject in need thereof a therapeutically effective amount of SEQ ID NO: 9 of WO’387 and the anticancer therapeutic agent of trastuzumab-MCC-DM 1 of US’302, wherein such treatment would predictably and desirably lead to the treatment of the cancer, wherein each compound would merely be expected to perform its art-recognized function in combination, as it does separately (see, e.g., MPEP § 2143(I)(A), (B), (G)).
No evidence of unexpected results commensurate in scope with the requirements of MPEP §§ 716, 716.01, and 716.02 have been placed on record to date.
Furthermore, there would be a reasonable expectation of success because the prior art is presumed fully enabled (see, e.g., MPEP § 2121(I)) for all that it discloses (see, e.g., MPEP §§ 2123(I)-(II)). Furthermore, it is well-within the ordinary skill in the art to practice known methods using known reagents to obtain the exact result taught and disclosed by the prior art.
Therefore, claims 1-3, 6-11, 14-17, and 19-20 are rejected.
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.
[NSDP Rejection 01]
Claims 1-3, 7-8, 14-15, 17, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. US10626155 (filed Jun. 22, 2012). Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The applicable analysis for Nonstatutory Double Patenting is set forth at MPEP § 804(II), and specifically at MPEP § 804(II)(B). Here, although the same invention is not being claimed twice (see, e.g., MPEP § 804(II)(A), discussing Statutory Double Patenting), a Nonstatutory Double Patenting rejection is appropriate because although the conflicting claims are not identical, at least one examined application claim is not patentably distinct from the reference claims because the examined application claim is either anticipated by, or would have been obvious over, the reference claims for the reasons set forth in the following paragraph[1]: Per MPEP § 804(II)(B), “To decide the question above, the examiner should first construe the claim(s) in the application under examination and the claim(s) in the reference application or patent to determine what are the differences”. MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). The following rejection is based upon an obviousness analysis. Accordingly, a comparison of the teachings of the reference claims and the instant pending claims are set forth below:
The issued claims and pending claims are not patentably distinct. Regarding instant claims 1, 14-15, 20, the issued claims are directed to pharmaceutical compositions (see, e.g., US’155 at claims 7-8), that are “for treating cancer in a subject by an administration by injection” (see, e.g., US’155 at claim 8), wherein the issued claim scope encompasses polypeptides comprising instant SEQ ID NO: 9 (compare instant claims and SEQ ID NO: 9 with US’155 at claim 1 and SEQ ID NO: 17 showing 100% sequence identity). Accordingly, although the claims are directed to products, an artisan would at once understand that such compounds were “for treating cancer in a subject by an administration by injection” (see, e.g., US’155 at claim 8). Regarding instant claims 1-3, 7-8, and the simultaneous or sequential administration of a cytotoxic compound, per MPEP § 804(II)(B)(1), in determining double patenting issues, an Examiner can rely on the Specification for identification of obvious variants (see, e.g., MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”)7. Here, US’155 discloses obvious variants, namely US’155 expressly identifies that “In seventh aspect, the present invention relates to the products containing: (i) an immunocytokine as describe above…, and (ii) a therapeutic agent, preferably an anticancer agent, as a combined preparation for simultaneous, separate, or sequential use for treating cancer in a subject” (see, e.g., US’155 at col. 3 at lines 25-45, col. 20 at line 35 to col. 21 at line 7). Furthermore, the “therapeutic agent, preferably an anticancer agent” would be readily understood to mean at least bleomycin, cyclophosphamide, cisplatin, oxaliplatin, doxorubicin, paclitaxel, vinblastine (i.e., a vinca alkaloid), and topotecan (i.e., an art-recognized topoisomerase I inhibitors) (see, e.g., US’155 at col. 19 at line 59 to col. 20 at line 17), wherein “subject” includes any mammals including rodents and humans (see, e.g., US’155 at col. 20 at lines 40-45). Accordingly, methods of treating cancer by administering such agents is understood to be an obvious variant of the pending claims. Regarding claim 17 and “administered subcutaneously (s.c.) or intraperitoneally (i.p.)”, the issued claims are directed to pharmaceutical compositions (see, e.g., US’155 at claims 7-8), that are “for treating cancer in a subject by an administration by injection” (see, e.g., US’155 at claim 8), wherein “administration by injection” would be readily understood to include intravenous and subcutaneous administration routes (see, e.g., US’155 at claim 8, col. 18 at lines 1-25, noting that pharmaceutical compositions can be formulated for intravenous and subcutaneous administration routes; per MPEP § 804(II)(B)(1), it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim in a double patenting rejection). Regarding claim 19 and the treatment of solid or hematological cancer, the issued claims are directed to pharmaceutical compositions (see, e.g., US’155 at claims 7-8), that are “for treating cancer in a subject by an administration by injection” (see, e.g., US’155 at claim 8), wherein “cancer” is not limited to a specific type of cancer, and would therefore be understood to include all types, including solid and non-solid cancers.
Accordingly, the differences between the reference claims and instant claims appear to be minor at best because both claim sets read upon known compounds having known uses in known methods [2]; and therefore the answer to the question “Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent”[3] is clearly “yes”. MPEP § 804(II)(B)(2)-(3) further identify that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)).
Obviousness analysis: Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims attempt to claim a different invention that amounts to an obvious variant of the issued claims, wherein both claim sets read upon species of the same agonist for use in methods of treating cancer, wherein the addition of another anticancer agent is an obvious variant of the issued claims and therefore would be expected to achieve the same predicted and expected outcomes (see, e.g., MPEP § 804(II)(B)(3)(B)). Accordingly, the present claims are directed to obvious variants of the representative claims because it is well-within the ordinary skill in the art to known compounds in known methods (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(A), (B), and (G)). Therefore, the instant claims are directed to obvious variants of the issued claims.
As issued claims in a U.S. patent, the reference claims are presumed to satisfy all statutory requirements in the absence of evidence to the contrary. Accordingly, the instant claims are directed to an obvious, claimed variant of the patent claims, namely the instant claims are directed to a named, claimed species set forth in the issued claims.
As required at (C) of MPEP § 804(II), the rejection is not prohibited by 35 U.S.C. 121.
As noted at MPEP § 804(II)(B)(4), the issued patent and the instant Application are understood to require only a one-way test for distinctiveness.
Accordingly, instant claims 1-3, 7-8, 14-15, 17, and 19-20 are rejected.
[NSDP Rejection 02]
Claims 1-3, 7-8, 14-15, 17, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-5 of U.S. Patent No. US10899816 (published Jan. 26, 2021). Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The applicable analysis for Nonstatutory Double Patenting is set forth at MPEP § 804(II), and specifically at MPEP § 804(II)(B). Here, although the same invention is not being claimed twice (see, e.g., MPEP § 804(II)(A), discussing Statutory Double Patenting), a Nonstatutory Double Patenting rejection is appropriate because although the conflicting claims are not identical, at least one examined application claim is not patentably distinct from the reference claims because the examined application claim is either anticipated by, or would have been obvious over, the reference claims for the reasons set forth in the following paragraph[1]: Per MPEP § 804(II)(B), “To decide the question above, the examiner should first construe the claim(s) in the application under examination and the claim(s) in the reference application or patent to determine what are the differences”. MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). The following rejection is based upon an obviousness analysis. Accordingly, a comparison of the teachings of the reference claims and the instant pending claims are set forth below:
Regarding instant claims 1, 14-15, 20, the issued claims are directed to pharmaceutical compositions (see, e.g., US’816 at claims 1-5; see esp. id. at claims 1-2 and 4), that are “for use for treating cancer in a subject, wherein the pharmaceutical composition is adapted to be administrable by injection by an administration by injection” (see, e.g., id. at claim 4), wherein the issued claim scope encompasses polypeptides comprising instant SEQ ID NO: 9 (compare instant claims and SEQ ID NO: 9 with US’816 at claim 1 and SEQ ID NO: 17 showing 100% sequence identity). Accordingly, although the issued claims are directed to products, an artisan would at once understand that such compounds were “for use for treating cancer in a subject, wherein the pharmaceutical composition is adapted to be administrable by injection by an administration by injection” (see, e.g., US’816 at claim 4). Regarding instant claims 1-3, 7-8, and the simultaneous or sequential administration of a cytotoxic compound, per MPEP § 804(II)(B)(1), in determining double patenting issues, an Examiner can rely on the Specification for identification of obvious variants (see, e.g., MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”)8. Here, US’816 discloses obvious variants, namely US’816 expressly identifies that “In seventh aspect, the present invention relates to the products containing: (i) an immunocytokine as describe above…, and (ii) a therapeutic agent, preferably an anticancer agent, as a combined preparation for simultaneous, separate, or sequential use for treating cancer in a subject” (see, e.g., US’816 at col. 3 at lines 20-45, col. 20 at line 35 to col. 21 at line 7). Furthermore, the “therapeutic agent, preferably an anticancer agent” would be readily understood to mean at least bleomycin, cyclophosphamide, cisplatin, oxaliplatin, doxorubicin, paclitaxel, vinblastine (i.e., a vinca alkaloid), and topotecan (i.e., an art-recognized topoisomerase I inhibitors) (see, e.g., US’816 at col. 19 at line 59 to col. 20 at line 17), wherein “subject” includes any mammals including rodents and humans (see, e.g., US’816 at col. 20 at lines 40-45). Accordingly, methods of treating cancer by administering such agents is understood to be an obvious variant of the pending claims. Regarding claim 17 and “administered subcutaneously (s.c.) or intraperitoneally (i.p.)”, the issued claims are directed to pharmaceutical compositions (see, e.g., US’816 at claims 4), that are for use for treating cancer in a subject, wherein the pharmaceutical composition is adapted to be administrable by injection by an administration by injection” (see, e.g., US’816 at claim 4). , wherein “administrable by injection” would be readily understood to include intravenous and subcutaneous administration routes (see, e.g., US’816 at claim 4, col. 18 at lines 1-25, noting that pharmaceutical compositions can be formulated for intravenous and subcutaneous administration routes; per MPEP § 804(II)(B)(1), it is permissible to use the specification as a dictionary to learn the meaning of a term in a claim in a double patenting rejection). Regarding claim 19 and the treatment of solid or hematological cancer, the issued claims are directed to pharmaceutical compositions (see, e.g., US’816 at claim 4), that are “for treating cancer in a subject” (see, e.g., US’816 at claim 8), wherein “cancer” is not limited to a specific type of cancer, and would therefore be understood to include all types, including solid and non-solid cancers.
Accordingly, the differences between the reference claims and instant claims appear to be minor at best because both claim sets read upon known compounds having known uses in known methods [2]; and therefore the answer to the question “Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent”[3] is clearly “yes”. MPEP § 804(II)(B)(2)-(3) further identify that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)).
Obviousness analysis: Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims attempt to claim a different invention that amounts to an obvious variant of the issued claims, wherein both claim sets read upon species of the same agonist for use in methods of treating cancer, wherein the addition of another anticancer agent is an obvious variant of the issued claims and therefore would be expected to achieve the same predicted and expected outcomes (see, e.g., MPEP § 804(II)(B)(3)(B)). Accordingly, the present claims are directed to obvious variants of the representative claims because it is well-within the ordinary skill in the art to known compounds in known methods (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(A), (B), and (G)). Therefore, the instant claims are directed to obvious variants of the issued claims.
As issued claims in a U.S. patent, the reference claims are presumed to satisfy all statutory requirements in the absence of evidence to the contrary. Accordingly, the instant claims are directed to an obvious, claimed variant of the patent claims, namely the instant claims are directed to a named, claimed species set forth in the issued claims.
As required at (C) of MPEP § 804(II), the rejection is not prohibited by 35 U.S.C. 121.
As noted at MPEP § 804(II)(B)(4), the issued patent and the instant Application are understood to require only a one-way test for distinctiveness.
Accordingly, instant claims 1-3, 7-8, 14-15, 17, and 19-20 are rejected.
[NSDP Rejection 03]
Claims 1-3, 7-8, 14-15, 17, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7 of U.S. Patent No. US11,273,204 B2 (published Mar. 15, 2022). Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The applicable analysis for Nonstatutory Double Patenting is set forth at MPEP § 804(II), and specifically at MPEP § 804(II)(B). Here, although the same invention is not being claimed twice (see, e.g., MPEP § 804(II)(A), discussing Statutory Double Patenting), a Nonstatutory Double Patenting rejection is appropriate because although the conflicting claims are not identical, at least one examined application claim is not patentably distinct from the reference claims because the examined application claim is either anticipated by, or would have been obvious over, the reference claims for the reasons set forth in the following paragraph[1]: Per MPEP § 804(II)(B), “To decide the question above, the examiner should first construe the claim(s) in the application under examination and the claim(s) in the reference application or patent to determine what are the differences”. MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). The following rejection is based upon an obviousness analysis. Accordingly, a comparison of the teachings of the reference claims and the instant pending claims are set forth below:
Regarding instant claims 1, 14-15, 20, the issued claims are directed to pharmaceutical compositions (see, e.g., US’204 at claims 1-7; see esp. id. at claim 7), wherein the issued claim scope encompasses polypeptides comprising instant SEQ ID NO: 9 (compare instant claims and SEQ ID NO: 9 with US’204 at claims 1, 6, and SEQ ID NO: 19, noting that SEQ ID NO: 19 and instant SEQ ID NO: 9 are identical). Regarding instant claims 1-3, 7-8, 17, and the simultaneous or sequential administration of a cytotoxic compound in a method of treating cancer, per MPEP § 804(II)(B)(1), in determining double patenting issues, an Examiner can rely on the Specification for identification of obvious variants (see, e.g., MPEP § 804(II)(B)(1), “those portions of the specification which provide support for the reference claims may also be examined and considered when addressing the issue of whether a claim in the application defines an obvious variation of an invention claimed in the reference patent or application”)9. Here, US’204 discloses obvious variants, namely US’204 expressly identifies that “In seventh aspect, the present invention relates to the products containing: (i) an immunocytokine as describe above…, and (ii) a therapeutic agent, preferably an anticancer agent, as a combined preparation for simultaneous, separate, or sequential use for treating cancer in a subject” (see, e.g., US’204 at col. 2 at lines 34-41, col. 19 at line 52 to col. 20 at line 3). Furthermore, the “therapeutic agent, preferably an anticancer agent” would be readily understood to mean at least bleomycin, cyclophosphamide, cisplatin, oxaliplatin, doxorubicin, paclitaxel, vinblastine (i.e., a vinca alkaloid), and topotecan (i.e., an art-recognized topoisomerase I inhibitors) (see, e.g., US’204at col. 19 at lines 8-35), wherein “subject” includes any mammals including rodents and humans (see, e.g., US’204 at col. 19 at lines 59-63), and wherein administration would be readily understood tin include intravenous and subcutaneous administration (see, e.g., US’204 at claim 4, col. 17 at lines 19-24). Accordingly, methods of treating cancer by administering such agents is understood to be an obvious variant of the pending claims. Regarding claim 19 and the treatment of solid or hematological cancer, the issued claims are directed to pharmaceutical compositions (see, e.g., US’204 at claims), that are for treating cancer in a subject” (see, e.g., US’204 at col. 2 at lines 34-41, col. 19 at line 52 to col. 20 at line 3), wherein “cancer” is not limited to a specific type of cancer, and would therefore be understood to include all types, including solid and non-solid cancers.
Accordingly, the differences between the reference claims and instant claims appear to be minor at best because both claim sets read upon known compounds having known uses in known methods [2]; and therefore the answer to the question “Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent”[3] is clearly “yes”. MPEP § 804(II)(B)(2)-(3) further identify that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)).
Obviousness analysis: Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims attempt to claim a different invention that amounts to an obvious variant of the issued claims, wherein both claim sets read upon species of the same agonist for use in methods of treating cancer, wherein the addition of another anticancer agent is an obvious variant of the issued claims and therefore would be expected to achieve the same predicted and expected outcomes (see, e.g., MPEP § 804(II)(B)(3)(B)). Accordingly, the present claims are directed to obvious variants of the representative claims because it is well-within the ordinary skill in the art to known compounds in known methods (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(A), (B), and (G)). Therefore, the instant claims are directed to obvious variants of the issued claims.
As issued claims in a U.S. patent, the reference claims are presumed to satisfy all statutory requirements in the absence of evidence to the contrary. Accordingly, the instant claims are directed to an obvious, claimed variant of the patent claims, namely the instant claims are directed to a named, claimed species set forth in the issued claims.
As required at (C) of MPEP § 804(II), the rejection is not prohibited by 35 U.S.C. 121.
As noted at MPEP § 804(II)(B)(4), the issued patent and the instant Application are understood to require only a one-way test for distinctiveness.
Accordingly, instant claims 1-3, 7-8, 14-15, 17, and 19-20 are rejected.
[NSDP Rejection 04]
Claims 1-3, 6-11, 14-17, and 19-20 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-26 of U.S. Patent No. US 11401312 B2 (published Aug. 2, 2022). Although the claims at issue are not identical, they are not patentably distinct from each other as explained below.
Claim interpretation: The applicable claim interpretation has been set forth in a preceding section above, and those interpretations are incorporated into the instant rejection. Additional claim interpretations are set forth below.
The applicable analysis for Nonstatutory Double Patenting is set forth at MPEP § 804(II), and specifically at MPEP § 804(II)(B). Here, although the same invention is not being claimed twice (see, e.g., MPEP § 804(II)(A), discussing Statutory Double Patenting), a Nonstatutory Double Patenting rejection is appropriate because although the conflicting claims are not identical, at least one examined application claim is not patentably distinct from the reference claims because the examined application claim is either anticipated by, or would have been obvious over, the reference claims for the reasons set forth in the following paragraph[1]: Per MPEP § 804(II)(B), “To decide the question above, the examiner should first construe the claim(s) in the application under examination and the claim(s) in the reference application or patent to determine what are the differences”. MPEP § 804(II)(B)(2)-(3) identifies that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)). The following rejection is based upon an obviousness analysis. Accordingly, a comparison of the teachings of the reference claims and the instant pending claims are set forth below:
Regarding instant claims 1, 14-15, 20, the issued claims are directed to methods of administering pharmaceutical compositions to humans (see, e.g., US’312 at claims 1-26), including to humans having metastatic cancers (see, e.g., US’312 at claim 4), wherein the pharmaceutical compositions may comprise polypeptides such as SEQ ID NO: 17 of US’ 312 (see, e.g., US’312 at claims 1, 10, 24-28, and SEQ ID NO: 17); which is identical to instant SEQ ID NO: 9 (compare instant SEQ ID NO: 9 with US’312 at SEQ ID NO: 17, showing 100% identity), wherein the compound may be administered parenterally or intravenously (see, e.g., US’312 at claim 12). Regarding claim 19 and the treatment of solid or hematological cancer, the issued claims are directed to methods of treating patients with any form of metastatic cancer (see, e.g., US’312 at claim 4), which would be understood to cover any solid or non-solid metastatic cancers.
The issued claims differ from the instantly pending claims scope as follows: The issued claims recite a method that does not specifically include or exclude the simultaneous treatment of such metastatic cancer patients with an additional anticancer therapeutic agent, such as trastuzumab emtansine.
However, such differences do not patentably distinguish the claims in view of the issued claims because such differences are obvious in view of the prior art. Specifically, US2012/0107302A1 pertains to the treatment of cancers, including metastatic breast cancer (see, e.g., US’302 at claim 46) by administering trastuzumab-MCC-DM 1. Regarding instant claims 1-3, 6, 9-10, 11, 16, and trastuzumab emtansine, “trastuzumab emtansine” is also known in the art as “Trastuzumab-MCC-DM 1”10, which is a prior art element, and art-recognized antibody-drug conjugate, wherein DM1 is a maytansinoid and Trastuzumab is a HER2-directed antibody (see, e.g., US’302 at ¶¶[0002], [0006], [0082]-[0085]), wherein trastuzumab-MCC-DM 1 is a “first-in-class HER2 antibody-drug conjugate (ADC)” used to treat patients “with HER2+ metastatic breast cancer” (see id.; see also id. at ¶[0068]), which may be utilized in combination therapies with other drugs (see, e.g., US’302 at ¶¶[0007]), and administered “separately in alternation (alternating, sequential dosages)” (see, e.g., US’302 at ¶¶[0016]-[0017], [0065]-[0066]). Regarding instant claim 11 and HER positive cancer, US’302 expressly identifies that trastuzumab-MCC-DM 1 is a “first-in-class HER2 antibody-drug conjugate (ADC)” used to treat patients “with HER2+ metastatic breast cancer” (see, e.g. ,US’302 at ¶¶[0002], [0006], [0068], [0082]-[0085]). Therefore, an artisan would readily appreciate that such compounds could be utilized to treat patients having HER2-positive breast cancers. Regarding the elected species and the dosage of trastuzumab-MCC-DM 1 utilized, US’302 exemplifies the usage of trastuzumab-MCC-DM 1 in phase I studies at 3.6 mg/kg by IV infusion once every 3 weeks (see, e.g., US’302 at ¶¶[0086]).
Accordingly, the differences between the reference claims and instant claims appear to be minor at best because both claim sets read upon known compounds having known uses in known methods, and the only differences were already known and taught by the prior art [2]; and therefore the answer to the question “Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent”[3] is clearly “yes”. MPEP § 804(II)(B)(2)-(3) further identify that a Nonstatutory Double Patenting Rejection may be appropriate based upon either an anticipation analysis or an obviousness analysis (see, e.g., MPEP § 804(II)(B)(2)-(3)).
Obviousness analysis: Under an obviousness analysis (see, e.g., MPEP § 804(II)(B)(3)), it is noted that the scope and content of the patent claim relative to the application claims at issue have been discussed above (see, e.g., MPEP § 804(II)(B)(3)(A)), and that the differences are that the instant claims attempt to claim a different invention that amounts to an obvious variant of the issued claims, wherein both claim sets read upon species of the same agonist for use in methods of treating patients with metastatic cancer, wherein the only difference appears to be the inclusion of Trastuzumab-MCC-DM 1, which is a known prior art agent specifically taught for use in the treatment of metastatic cancer, and therefore the difference does not patentably distinguish the issued claims from the pending claims since the difference amounts to a known and predictably change using known elements taught for known purposes, wherein the difference would merely yield predicted and expected outcomes (i.e., the treatment of metastatic cancer in a patient) (see, e.g., MPEP § 804(II)(B)(3)(B)). Accordingly, the present claims are directed to obvious variants of the representative claims because it is well-within the ordinary skill in the art to known compounds in known methods (see, e.g., MPEP § 804(II)(B)(3)(C)-(D); see also MPEP §§ 2143(I)(A), (B), and (G), 2144.06(I)). Therefore, the instant claims are directed to obvious variants of the issued claims.
As issued claims in a U.S. patent, the reference claims are presumed to satisfy all statutory requirements in the absence of evidence to the contrary. Accordingly, the instant claims are directed to an obvious, claimed variant of the patent claims, namely the instant claims are directed to a named, claimed species set forth in the issued claims.
As required at (C) of MPEP § 804(II), the rejection is not prohibited by 35 U.S.C. 121.
As noted at MPEP § 804(II)(B)(4), the issued patent and the instant Application are understood to require only a one-way test for distinctiveness.
Claims 1-3, 6-11, 14-17, and 19-20 are rejected.
Pertinent Prior Art
The prior art made of record and not relied upon is considered pertinent to applicant's disclosure.
US2015/0224104A1 pertains to methods of treating breast cancer, including methods including the step of administering the antibody-drug conjugate of Trastuzumab-MCC-DM1 (see, e.g., US’907 at title, abs, claims, claim 15).
US2017/0035907A1 pertain to methods of treating types of HER-2 positive cancer by administering the antibody-drug conjugate of Trastuzumab-MCC-DM1 (see, e.g., US’907 at title, abs, claims).
US20160318986A1 corresponds to the issued patent of US 10626155, which has been applied under 35 USC 103 above. SEQ ID NO: 17 comprises instant SEQ ID NO: 9.
US20180312560A1 corresponds to the issued patent of US 10899816, which has been applied under 35 USC 103 above. SEQ ID NO: 17 comprises instant SEQ ID NO: 9.
US 11059876 discloses a variant of instant SEQ ID NO: 9 that shows 100% sequence identity with instant SEQ ID NO: 9 over 210 amino acids (not 211) (compare instant SEQ ID NO: 9 with SEQ ID NO: 8 of US’876).
US 10,808,022 discloses instant SEQ ID NO: 9 as SEQ ID NO: 17 (compare instant SEQ ID NO: 9 with SEQ ID NO: 17 of US’022).
US20190263877A1 discloses and pertains to treatments of cancer using IL-15 variants (see, e.g., US’877 at title, abs, claims).
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to RANDALL L BEANE whose telephone number is (571)270-3457. The examiner can normally be reached Mon.-Fri., 7 AM to 2 PM ET.
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/RANDALL L BEANE/Primary Examiner, Art Unit 1654
1 Cited in IDS filed 11/12/2025 as Cite No. 28.
2 Cited in IDS filed 11/12/2025 as Cite No. 28.
3 Cited in IDS filed 11/12/2025 as Cite No. 28.
4 See search notes entry for CAS Registry Number 1018448-65-1, identifying alternative names including Ado-trastuzumab emtansine, PRO 132365, RG 3502, T-DM 1, and Trastuzumab-MCC-DM 1.
5 See search notes entry for CAS Registry Number 1018448-65-1, identifying alternative names including Ado-trastuzumab emtansine, PRO 132365, RG 3502, T-DM 1, and Trastuzumab-MCC-DM 1.
6 See search notes entry for CAS Registry Number 1018448-65-1, identifying alternative names including Ado-trastuzumab emtansine, PRO 132365, RG 3502, T-DM 1, and Trastuzumab-MCC-DM 1.
[1] See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
7 See also Sun Pharmaceutical Industries, Ltd. v. Eli Lilly & Co., 611 F.3d 1381 (Fed. Cir. 2010), noting that “Similarly, in Pfizer, the earlier patent claimed several compounds and the specification disclosed their use in treating inflammation and inflammation-associated disorders. 518 F.3d at 1363 & n.9; see U.S. Patent No 5,563,165 (“’165 patent”), at [57], col.1 ll.11-14, col.3 ll.3-27. The later patent then claimed a method of using these compounds for treating inflammation, inflammation-associated disorders, and specific inflammation-associated disorders, including arthritis, pain, and fever. Pfizer, 518 F.3d at 1363 & n.9; see U.S. Patent No. 5,760,068 (“’068 patent”) col.97 l.49-col.108 l.29. After rejecting the patentee’s objection to our consideration of the specification of the earlier patent, we determined that the later patent “merely claims a particular use described in the [earlier] patent of the claimed compositions of the [earlier] patent.” Pfizer, 518 F.3d at 1363 & n.8. As such, we concluded that the asserted claims of the later patent were not “patentably distinct” from the claims of the earlier patent, and thus the later patent was invalid for obviousness-type double patenting. Id. at 1368.”
[2] See, e.g., MPEP § 804(II)(B), “To decide the question above, the examiner should first construe the claim(s) in the application under examination and the claim(s) in the reference application or patent to determine what are the differences
[3] See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
[1] See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
8 See also Sun Pharmaceutical Industries, Ltd. v. Eli Lilly & Co., 611 F.3d 1381 (Fed. Cir. 2010), noting that “Similarly, in Pfizer, the earlier patent claimed several compounds and the specification disclosed their use in treating inflammation and inflammation-associated disorders. 518 F.3d at 1363 & n.9; see U.S. Patent No 5,563,165 (“’165 patent”), at [57], col.1 ll.11-14, col.3 ll.3-27. The later patent then claimed a method of using these compounds for treating inflammation, inflammation-associated disorders, and specific inflammation-associated disorders, including arthritis, pain, and fever. Pfizer, 518 F.3d at 1363 & n.9; see U.S. Patent No. 5,760,068 (“’068 patent”) col.97 l.49-col.108 l.29. After rejecting the patentee’s objection to our consideration of the specification of the earlier patent, we determined that the later patent “merely claims a particular use described in the [earlier] patent of the claimed compositions of the [earlier] patent.” Pfizer, 518 F.3d at 1363 & n.8. As such, we concluded that the asserted claims of the later patent were not “patentably distinct” from the claims of the earlier patent, and thus the later patent was invalid for obviousness-type double patenting. Id. at 1368.”
[2] See, e.g., MPEP § 804(II)(B), “To decide the question above, the examiner should first construe the claim(s) in the application under examination and the claim(s) in the reference application or patent to determine what are the differences
[3] See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
[1] See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
9 See also Sun Pharmaceutical Industries, Ltd. v. Eli Lilly & Co., 611 F.3d 1381 (Fed. Cir. 2010), noting that “Similarly, in Pfizer, the earlier patent claimed several compounds and the specification disclosed their use in treating inflammation and inflammation-associated disorders. 518 F.3d at 1363 & n.9; see U.S. Patent No 5,563,165 (“’165 patent”), at [57], col.1 ll.11-14, col.3 ll.3-27. The later patent then claimed a method of using these compounds for treating inflammation, inflammation-associated disorders, and specific inflammation-associated disorders, including arthritis, pain, and fever. Pfizer, 518 F.3d at 1363 & n.9; see U.S. Patent No. 5,760,068 (“’068 patent”) col.97 l.49-col.108 l.29. After rejecting the patentee’s objection to our consideration of the specification of the earlier patent, we determined that the later patent “merely claims a particular use described in the [earlier] patent of the claimed compositions of the [earlier] patent.” Pfizer, 518 F.3d at 1363 & n.8. As such, we concluded that the asserted claims of the later patent were not “patentably distinct” from the claims of the earlier patent, and thus the later patent was invalid for obviousness-type double patenting. Id. at 1368.”
[2] See, e.g., MPEP § 804(II)(B), “To decide the question above, the examiner should first construe the claim(s) in the application under examination and the claim(s) in the reference application or patent to determine what are the differences
[3] See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
[1] See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
10 See search notes entry for CAS Registry Number 1018448-65-1, identifying alternative names including Ado-trastuzumab emtansine, PRO 132365, RG 3502, T-DM 1, and Trastuzumab-MCC-DM 1.
[2] See, e.g., MPEP § 804(II)(B), “To decide the question above, the examiner should first construe the claim(s) in the application under examination and the claim(s) in the reference application or patent to determine what are the differences
[3] See, e.g., MPEP § 804(II)(B), noting that “In determining whether a nonstatutory basis exists for a double patenting rejection, the first question to be asked is: Is any invention claimed in the application anticipated by, or an obvious variation of, an invention claimed in the patent? If the answer is yes, then a nonstatutory double patenting rejection may be appropriate.”
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