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 .
Applicant’s amendment, filed on 3/17/2025, is acknowledged.
Claims 1-24 are cancelled.
Claims 25-41 are currently pending.
Claims 25, 38, and 41 are independent claims.
Election/Restrictions
Applicants’ election without traverse of Group I, claims 25-37, directed to a method of treating a proliferative disorder comprising administration of an anti-CD19 PBD ADC, and the species of: i) a CD19 expressing cancer; ii) an individual undergoing polatuzumab vedotin treatment; and iii) non-Hodgkin’s Lymphoma, filed on 7/29/2026, is acknowledged.
Claim 32 is drawn to an unelected species of patient population.
Claims 32 and 38-41 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected inventions and/or species.
Claims 25-31 and 33-37 are under examination as being drawn to a method of treating a proliferative disorder comprising administration of an anti-CD19 PBD ADC.
Priority
Applicant’s claim for the benefit of a prior-filed United Kingdom application numbers GB2109373.7, filed 29 June 2021; GB2109375.2, filed 29 June 2021; and GB2109377.8, filed 29 June 2021, is acknowledged.
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 12/10/2024 and 7/29/2026 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner in their entireties.
Claim Objections
Claims 27, 29, 30, and 35 are objected to because of the following informalities:
Claim 27 currently recites “…wherein the anti-CD19 antibody comprises the complementarity-determining regions (CDRs) of SEQ ID NOs: 2 and 8”. However, SEQ ID NO: 2 and 8 are VH and VL regions and not CDRs. It is recommended to amend the claim to clarify that the anti-CD19 antibody comprises the CDR1, 2, and 3 from each of these VH and VL sequences, and not that the CDRs are SEQ ID NO: 2 and 8.
Claims 29, 30, and 35 currently recite “CD19+ve”, which is not a commonly used term. It is recommended to amend the claims to recite “CD19 expressing” in place of “CD19+ve” to clarify that the recited cells and/or tumor express CD19.
Appropriate correction is required.
Claim Rejections - 35 USC § 112
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 25-31 and 33-37 rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for methods of treating proliferative disorder characterized by cells expressing CD19 and CD79b in an individual comprising administration of polatuzumab vedotin and an anti-CD19 ADC comprising a PBD dimer and the anti-CD19 antibody structures of the RB4v1.0, RB4v1.2, B43, HD37, 4G7, and FMC63 clones, as defined by their amino acid sequences especially in the CDR regions critical for antigen binding, does not reasonably provide enablement for methods of treating any proliferative disorder regardless of CD19/CD79b expression status comprising administration of polatuzumab vedotin and a broad genus of anti-CD19 ADCs comprising a broad genus of antibodies with a partial structure at best and the function of “anti-CD19”. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Factors to be considered in determining whether undue experimentation is required to practice the claimed invention are summarized In re Wands (858 F2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988)). The factors most relevant to this rejection are the scope of the claim, the amount of direction or guidance provided, the lack of sufficient working examples, the unpredictability in the art and the amount of experimentation required to enable one of skill in the art to practice the claimed invention.
Breadth of claims and nature of invention:
Claims 25-31 and 33-37 encompass methods of treating any proliferative disease (claims 25-28, 31, 33, 34, 36, and 37) or CD19 expressing proliferative diseases (claims 29, 30, and 35) with a combination of an anti-CD19 ADC and polatuzumab vedotin.
Claims 25, 26, 28-31, and 33-37 additionally encompass methods of treating proliferative diseases comprising administration of ADC comprising antibodies with a partial structure at best and the function of “anti-CD19”.
The specification discloses a combination of ADCx19 and polatuzumab vedotin are effective at killing multiple cell lines in vitro, including DLBCL and Burkitt lymphoma cell lines such as Ramos, TMD8, and WSU-DLCL2 (Example 1). A combination of the anti-CD19 ADC loncastuximab tesirine and the anti-CD79b ADC polatuzumab vedotin were effective at reducing tumor growth in vivo Examples 2-4, Figure 1). The specification additionally discloses other antibody structures that bind to CD19, including the RB4v1.0, B43, HD37, 4G7, and FMC63 antibody structures (pg. 61-62, SEQ ID NO: 1-14).
Amount of direction and existence of working examples:
The specification discloses in vivo efficacy of loncastuximab tesirine and polatuzumab vedotin in reducing tumor growth of WSU-DLCL2 NHL cells (Example 2) as well as Ramos NHL (Example 3) The specification additionally discloses other working examples of anti-CD19 antibody structures that can specifically bind to CD19, which were the structures of the anti-CD19 antibody clones RB4v1.0, B43, HD37, 4G7, and FMC63 (pg. 61-62).
Level of predictability, state of prior art, and quantity of experimentation needed:
Regarding the broadly claimed genus of antibody structures with a partial structure at best and the function of “anti-CD19” (claims 25, 26, 28-31, and 33-37), the claims are directed to agents with little to no recited structure, all with the function of “anti-CD19”, which includes millions to billions of different structures with the recited function.
However, the specification did not give the skilled in the art enough information to choose candidate antigen binding structures from the vast number of options of millions of candidates, and therefore required scientists to engage in a great deal of experimentation and failure. “That is not enablement”—it is a “hunting license.”
The specification discloses seven different anti-CD19 antibody examples with the function of “anti-CD19”, all of which are specific structures with defined amino acid sequences especially in the CDR regions critical for antigen binding that give rise to the recited function.
In Amgen Inc. et al. v. Sanofi et al., 598 U.S. 594, 2023 USPQ2d 602 (2023), the Supreme Court held that claims drawn to a genus of monoclonal antibodies, which were functionally claimed by their ability to bind to a specific protein, PCSK9, were invalid due to lack of enablement. The claims at issue were functional, in that they defined the genus by its function (the ability to bind to specific residues of PCSK9) as opposed to reciting a specific structure (the amino acid sequence of the antibodies in the genus). The Supreme Court concluded that the patents at issue failed to adequately enable the full scope of the genus of antibodies that performed the function of binding to specific amino acid residues on PCSK9 and blocking the binding of PCSK9 to a particular cholesterol receptor, LDLR. This decision reaffirmed the prior decision made by the Federal District Court in Amgen Inc. v. Sanofi, Aventisub LLC., 987 F.3d 1080 (Fed. Cir. 2021).
The Court clarified that the specification does not always need to "describe with particularity how to make and use every single embodiment within a claimed class." Id. at 610-11. However, "[i]f a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class….The more one claims, the more one must enable." Id.
The specification may require a reasonable amount of experimentation to make and use the invention and what is reasonable will depend on the nature of the invention and the underlying art. For example, "it may suffice to give an example (or a few examples) if the specification also discloses some general quality … running through the class that gives it a peculiar fitness for the particular purpose" and "disclosing that general quality may reliably enable a person skilled in the art to make and use all of what is claimed, not merely a subset." Id. at 611 (internal quotations omitted). However, the Supreme Court found that Amgen failed to enable all that it claimed, even if allowing for a reasonable degree of experimentation. Id. at 613; see also Baxalta Inc. v Genentech, Inc., 81 F.4th 1362, 1367, 2023 USPQ2d 1103 (Fed. Cir. 2023) ("[t]he facts of this case are more analogous to—and are, in fact, indistinguishable from—those in Amgen. We do not interpret Amgen to have disturbed our prior enablement case law, including Wands and its factors."). Moreover, "[w]e see no meaningful difference between Wands' ‘undue experimentation’ and Amgen's ‘[un]reasonable experimentation’ standards. Id. at footnote 4. See also Guidelines for Assessing Enablement in Utility Applications and Patents in View of the Supreme Court Decision in Amgen Inc. et al. v. Sanofi et al., 89 FR 1563 (January 10, 2024), which explains that regardless of the technology the Wands factors should be used when assessing enablement.
However, while the specification in Amgen identified 26 exemplary antibodies that performed the claimed function by their amino acid sequences, the claims at issue were directed to a class which included "a ‘vast’ number of additional antibodies" that Amgen had not described by their amino acid sequences. Id. at 613. The Court found that Amgen sought to monopolize an entire class by their function, even though that class was much broader than the 26 exemplary antibodies disclosed by their amino acid structure. Id. at 613.
In Amgen Inc. v. Sanofi, Aventisub LLC, 987 F.3d 1080 (Fed. Cir. 2021), which the Supreme Court affirmed, the Federal Circuit explicitly applied the Wands factors to assess whether the specification of Amgen’s patent provided sufficient enablement, for purposes of 35 U.S.C. 112(a), to make and use the full scope of the claimed invention. The court relied on evidence showing that the scope of the claims encompassed millions of antibodies and that it was necessary to screen each candidate antibody in order to determine whether it met the functional limitations of the claim. Id. at 1088. Consequently, the Federal Circuit concluded that there was a lack of enablement. See also the following cases across various technology areas: McRO, Inc. v. Bandai Namco Games Am. Inc., 959 F.3d 1091, 2020 USPQ2d 10550 (Fed. Cir. 2020); Wyeth & Cordis Corp. v. Abbott Laboratories, 720 F.3d 1380, 107 USPQ2d 1273 (Fed. Cir. 2013); Enzo Life Sciences, Inc. v. Roche Molecular Systems, Inc., 928 F.3d 1340 (Fed. Cir. 2019); and Idenix Pharmaceuticals LLC v. Gilead Sciences Inc., 941 F.3d 1149, 2019 USPQ2d 415844 (Fed. Cir. 2019).
Amgen attempted to claim an entire class of compounds by their function, namely antibodies that bind to the “sweet spot” of PCSK9 thereby inhibiting it from binding to LDL, while only describing 26 amino acid sequences in its specification. The two processes, the “roadmap” and “conservative substitution” did not save Amgen. According to the Court, these amounted to “little more than two research assignments” which forced scientists to conduct “painstaking experimentation” to see what worked. (citing Incandescent Lamp). The Court therefore held that Amgen’s specification did not enable the claims.
This case is akin to the issue in Amgen Inc. v. Sanofi, Aventisub LLC, in which the court relied on evidence showing that the scope of the claims encompassed millions of antibodies and that it was necessary to screen each candidate antibody in order to determine whether it met the functional limitations of the claim. Sanofi-Aventisub at 1088. Consequently, the Federal Circuit concluded that there was a lack of enablement. While the specification in Amgen identified 26 exemplary antibodies that performed the claimed function by their amino acid sequences, the claims at issue were directed to a class that included “a ‘vast' number of additional antibodies” that Amgen had not described by their amino acid sequences. Id. at 1256. The Supreme Court found that Amgen sought to monopolize an entire class of antibodies by their function, which was much broader than the 26 exemplary antibodies disclosed by their amino acid structure.
In the instant case, the claims are directed to a broad class of antibodies with a partial structure at best and the function of “anti-CD19”. The specification discloses six anti-CD19 structures with this recited function.
The instant claims are directed to classes of polypeptides that include “a ‘vast’ number” of additional structures (i.e., amino acid sequences of all of the CDR regions that are necessary for antigen binding) in which the instant specification fails to describe. It would be necessary to first generate and then screen each candidate agent to determine whether or not it met the function limitations of “anti-CD19”. The Federal Circuit concluded that there was a lack of enablement, which was affirmed by the Supreme Court in Amgen.
The instant specification does not disclose any common structural feature delineating which other antibody structures would have the function of “anti-CD19”. The only structure-function relationship guidance the specification provides is to disclose individual examples of anti-CD19 antibody structures with this function.
The instant claims simply direct skilled artisans to engage in the same iterative, trial-and-error process the inventors followed to discover the antibody structures they elected to disclose and that “[u]nder Amgen, such random trial-and-error discovery, without more, constitutes unreasonable experimentation that falls outside the bounds required by § 112(a).” Id. at *8, *10.
Applicant is relying upon certain biological activities such as CD19 binding antibodies and a limited number of species with defined structures (e.g. amino acid sequences) to support an entire genus of diverse and structurally unrelated inhibitory polypeptide structures. Yet the instant specification does not provide sufficient guidance and directions as to the structural features of the polypeptide structures and the correlation between the structure and the desired antigen binding and inhibitory function.
The Supreme Court’s 2023 decision in Amgen v. Sanofi, which mainly involves the enablement requirement, states that “where a patentee purports to invent an entire genus, it must enable the entire genus”; “disclosing how to produce some antibodies that perform a specified function is not equivalent to disclosing how to produce all such antibodies – and it is the latter that petitioners claim as their invention”; S. Ct.
Additionally, in its recent decision in Baxalta Inc. v. Genentech, Inc., No. 2022-1461, 2023 WL 6135930 (Fed. Cir. Sept. 20, 2023) the Federal Circuit found the facts of this case to be "materially indistinguishable from those in Amgen." Baxalta, 2023 WL 6135930, at *4. According to the Federal Circuit, claim 1 covers "millions of potential candidate antibodies" (id.) that bind to Factor IX/IXa and increase the procoagulant activity of Factor IXa. The court, however, noted that the specification discloses the amino acid sequence of just 11 of those antibodies. And like the roadmap in the patents at issue in Amgen, "the '590 patent's roadmap simply directs skilled artisans to engage in the same iterative, trial-and-error process the inventors followed to discover the [11] antibodies they elected to disclose." (Id.) Missing from the specification, according to the Federal Circuit, was "'a quality common to every functional embodiment' ... that would allow a skilled artisan to predict which antibodies will perform the claimed functions" (id.; quoting Amgen Inc. v. Sanofi., 598 U.S. 594, 614 (2023)), such as a common structural or other feature that would allow the antibodies to perform the claimed functions, or an explanation as to why the 11 antibodies do so and others do not. (Baxalta, 2023 WL 6135930, at *4). And the Federal Circuit was not persuaded by Baxalta's argument that its disclosed hybridoma-and screening process "predictably and reliably generates new claimed antibodies every time it is performed" (id.), because "it is undisputed that to practice the full scope of the claimed invention, skilled artisans must make candidate antibodies and screen them to determine which ones perform the claimed functions." (Id.).
Regarding the broadly claimed methods of treating any proliferative disease regardless of CD19/CD79b expression (claims 25-28, 31, 33, 34, 36, and 37) or CD19 expressing disease (claims 29, 30, and 35) with a combination of polatuzumab vedotin and an anti-CD19 ADC comprising an anti-CD19 antibody and a PBD dimer, the instant specification discloses treatment of two different lymphoma cell lines with a combination of polatuzumab vedotin and loncastuximab tesirine, which were the WSU-DLCL2 and Ramos cell lines (Examples 3 and 4). The current state of the art teaches that these cell lines can be targeted by both agents because the cell lines express both CD19 and CD79b, which are the cell surface targets that the claimed combination therapy specifically binds to for drug delivery.
For example, Ryan et al. (Blood. 2017 Nov 2;130(18):2018-2026. doi: 10.1182/blood-2017-04-779389) teaches CD19 is expressed by both the Ramos and WSU-DLCL2 cell lines express CD19 and can be targeted by anti-CD19 antibody drug conjugates (pg. 2020): “…SGN-CD19B was evaluated in preclinical models of B-cell malignancies including 3 subcutaneous models of B-NHL and 1 disseminated model of B-ALL. Among the B-NHL models, we selected WSUDLCL2, Ramos, and DoHH2 cell lines, which are derived from DLBCL, Burkitt, and follicular lymphoma, respectively. Figure 4A-C shows that treatment of mice bearing subcutaneous lymphoma xenografts with a single dose of SGN-CD19B at 100 mg/kg results in significant tumor growth delay…”. Li et al. (Br J Pharmacol. 2019 Oct;176(19):3805-3818. doi: 10.1111/bph.14784) further teaches that WSU-DLCL2 cells express human CD79b (Section 3.6): “…WSU-DLCL2, which only expresses humanCD79b.” He et al. (EMBO J. 2018 Jun 1;37(11):e97980. doi: 10.15252/embj.201797980) further teaches that Ramos cells express both CD19 and CD79b (Abstract): “…Ramos B cells require the expression of the BCR signaling component Igß (CD79b), and the co-receptor CD19, for their fitness and competitive growth…”
Given that these cell lines were already known to co-express both CD19 and CD79b, there is a reasonable expectation of success that therapies targeting both epitopes would successfully treat such cancers. Additionally, there would be a reasonable expectation of success in treating proliferative disorders characterized by cells that express both CD19 and CD79b with a combination of polatuzumab vedotin and an anti-CD19 ADC comprising an anti-CD19 antibody and a PBD dimer. However, neither the instant specification nor the prior art provides sufficient guidance to treat diseases or disorders in which these antigens are not expressed, as the targets for the combination therapy are not longer present to direct the antibody drug conjugates to, for example, tumor cells in vivo.
The specification does not reasonably provide enablement to make and use the invention of instant claims 25-31 and 33-37. The specification does enable one with ordinary skill to make the antibody clone discussed supra.
Reasonable correlation must exist between the scope of the claims and scope of the enablement set forth. In view on the quantity of experimentation necessary the limited working examples, the nature of the invention, the state of the prior art, the unpredictability of the art and the breadth of the claims, it would take undue trials and errors to practice the claimed invention.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
Claims 25-29, 31, and 35-37 are rejected under 35 U.S.C. 103 as being unpatentable over Van Berkel et al. (WO2014057117) in view of Palanca-Wessels et al. (Lancet Oncol. 2015 Jun;16(6):704-15. doi: 10.1016/S1470-2045(15)70128-2).
Claim 25 claims a method of treating a proliferative disorder in an individual comprising administration of polatuzumab vedotin and an anti-CD19 ADC comprising an anti-CD19 antibody and a PDB dimer recited in formula (III).
Van Berkel et al. teaches PBD dimer anti-CD19 antibody drug conjugates comprising the ConjE structure, wherein Ab is an anti-CD19 antibody (pg. 8, claim 2):
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Van Berkel et al. additionally teaches methods of treating proliferative diseases such as Non-Hodgkin’s Lymphoma comprising administration of an anti-CD19 ADC comprising the RB4v1.2 antibody clone fused to the ConjE structure (Examples 12 and 13, Fig. 2 and 3, Claim 114):
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Van Berkel et al. teaches that the anti-CD19 ADC is effective against both DLBCL (Example 3) and Burkitt’s Lymphoma (Example 4) subtypes of NHL.
Van Berkel et al. does not teach administration of the anti-CD19 ConjE ADC and polatuzumab vedotin (i.e., the limitations of instant claim 1).
Palanca-Wessels et al., in the same field of endeavor, teaches administration of polatuzumab vedotin to a subject to treat NHL including the DLBCL subtype (Methods, Fig. 1 and 3): “…identify the recommended phase 2 dose of polatuzumab vedotin as a single agent and in combination with rituximab. A 3 + 3 dose-escalation design was used in which we treated patients with polatuzumab vedotin (0·1–2·4 mg/kg every 21 days) in separate dose-escalation cohorts for NHL and CLL. After determination of the recommended phase 2 dose, we enrolled patients with relapsed or refractory diff use large B-cell lymphoma and relapsed or refractory indolent NHL into indication-specific cohorts…”
It would have been obvious to one with ordinary skill in the art, before the effective filing date of the instant application, to have combined the methods of treating NHL taught by Van Berkel et al. and Palanca-Wessels et al. with a reasonable expectation of success, as the references each teach methods of treating NHL in an individual that one with ordinary skill in the art would be able to combine, for example by administering both agents. One would have been motivated to make this change to develop a more effective method of treating NHL. Additionally, it is prima facie obvious to combine two compositions each of which is taught by prior art to be useful for same purpose in order to form third composition that is to be used for very same purpose; the idea of combining them flows logically from their having been individually taught in prior art. In re Kerkhoven, 205 USPQ 1069, CCPA 1980. See MPEP 2144.06. In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
The combined references teach a method of treating NHL (i.e., a proliferative disorder) comprising administering an individual polatuzumab vedotin and RB4v1.2-ConjE anti-CD19 ADC, meeting the limitations of instant claims 25, 26, 36, and 37.
Regarding claim 27, Van Berkel et al. teaches the RB4v1.2 anti-CD19 comprise the VH of SEQ ID NO: 2 and VL of SEQ ID NO: 8. SEQ ID NO: 2 of Van Berkel et al. is 100% identical with instant SEQ ID NO: 2:
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SEQ ID NO: 8 of Van Berkel et al. is 100% identical with instant SEQ ID NO: 8, meeting the claim limitations:
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Regarding claim 28, Van Berkel et al. teaches the subject is a human (pg. 93, lines 13-14), and Palanca-Wessels et al. teaches the subject is a human (“Study design and patients” section), meeting the claim limitations.
Regarding claims 29 and 35, Van Berkel et al. teaches that the NHL cancer cells express CD19 (pg. 170, lines 1-3), meeting the claim limitations.
Regarding claim 31, Palanca-Wessels et al. teaches patients undergoing treatment with polatuzumab vedotin (Abstract), meeting the claim limitations.
Therefore, the invention as a whole was prima facie obvious to one of ordinary skill in the art at the time the invention was made, as evidenced by the references, especially in the absence of evidence to the contrary.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 25-29, 31, and 35-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 9,931,414 (Pat ‘414) in view of Van Berkel et al. (WO2014057117, supra) and Palanca-Wessels et al. (Lancet Oncol. 2015 Jun;16(6):704-15. doi: 10.1016/S1470-2045(15)70128-2, supra). Although the claims at issue are not identical, they are not patentably distinct from each other.
Pat ‘414 claims anti-CD19 ADCs comprising an anti-CD19 antibody and the ConjE PBD conjugate (claim 1):
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Pat ‘414 additionally claims the anti-CD19 antibody comprises the VH of SEQ ID NO: 2 and the VL of SEQ ID NO: 8 (claim 2). SEQ ID NO: 2 of Pat ‘414 is 100% identical with instant SEQ ID NO: 2:
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SEQ ID NO: 8 of Pat ‘414 is 100% identical with instant SEQ ID NO: 8:
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Pat ‘414 additionally claims methods of treating CD19 overexpressing cancers comprising administration of the anti-CD19 ADC (claim 11).
Van Berkel et al., in the same field of endeavor, teaches that the same anti-CD19 antibodies as claimed in Pat ‘414 can be used in methods of treating NHL (Examples 12 and 13, Fig. 4).
Palanca-Wessels et al., in the same field of endeavor, teaches administration of polatuzumab vedotin to a subject to treat NHL including the DLBCL subtype (Methods, Fig. 1 and 3): “…identify the recommended phase 2 dose of polatuzumab vedotin as a single agent and in combination with rituximab. A 3 + 3 dose-escalation design was used in which we treated patients with polatuzumab vedotin (0·1–2·4 mg/kg every 21 days) in separate dose-escalation cohorts for NHL and CLL. After determination of the recommended phase 2 dose, we enrolled patients with relapsed or refractory diff use large B-cell lymphoma and relapsed or refractory indolent NHL into indication-specific cohorts…”
It would have been obvious to one with ordinary skill in the art to modify the invention of Pat ‘414 in view of Van Berkel et al. and Palanca-Wessels et al. to use the anti-CD19 ADC claimed by Pat ‘414 to treat proliferative diseases such as NHL in combination with polatuzumab vedotin with a reasonable expectation of success, as Van Berkel et al. teaches the ADC of Pat ‘414 is used in methods of treating NHL, and Palanca-Wessels et al. teaches polatuzumab vedotin is used to treat NHL as well. One would expect both agents to function normally in treating NHL. One would have been motivated to make this change to develop a more effective method of treating NHL. Additionally, it is prima facie obvious to combine two compositions each of which is taught by prior art to be useful for same purpose in order to form third composition that is to be used for very same purpose; the idea of combining them flows logically from their having been individually taught in prior art. In re Kerkhoven, 205 USPQ 1069, CCPA 1980. See MPEP 2144.06. In re Couvaras, 70 F.4th 1374, 1378-79, 2023 USPQ2d 697 (Fed. Cir. 2023) (That the two claimed types of active agents, GABA-a agonists and ARBs, were known to be useful for the same purpose—alleviating hypertension—alone can serve as a motivation to combine).
The combined references teach a method of treating NHL (i.e., a proliferative disorder) comprising administering an individual polatuzumab vedotin and the same anti-CD19 ADC structure recited in instant claim 27, meeting the limitations of instant claims 25-27, 36, and 37.
Regarding claim 28, Van Berkel et al. teaches the subject is a human (pg. 93, lines 13-14), and Palanca-Wessels et al. teaches the subject is a human (“Study design and patients” section), meeting the claim limitations.
Regarding claims 29 and 35, Van Berkel et al. teaches that the NHL cancer cells express CD19 (pg. 170, lines 1-3), meeting the claim limitations.
Regarding claim 31, Palanca-Wessels et al. teaches patients undergoing treatment with polatuzumab vedotin (Abstract), meeting the claim limitations.
Therefore, the invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘414 in view of Van Berkel et al. and Palanca-Wessels et al., especially in absence of evidence to the contrary.
Claims 25-29, 31, and 35-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 10,780,181 (Pat ‘181) in view of Van Berkel et al. (supra) and Palanca-Wessels et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other.
Pat ‘181 claims anti-CD19 ADCs comprising an anti-CD19 antibody and the ConjE PBD conjugate (claim 1):
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Pat ‘181 additionally claims the anti-CD19 antibody comprises the VH of SEQ ID NO: 1 and the VL of SEQ ID NO: 7 (claim 1). SEQ ID NO: 1 of Pat ‘181 has the same CDRs as instant SEQ ID NO: 2 (CDR regions in bold):
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SEQ ID NO: 7 of Pat ‘181 is 100% identical with instant SEQ ID NO: 8:
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Pat ‘181 additionally claims methods of treating CD19 overexpressing cancers comprising administration of the anti-CD19 ADC (claim 9).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘181 in view of Van Berkel et al. and Palanca-Wessels et al. for the same reasons discussed for Pat ‘414 supra, especially in absence of evidence to the contrary.
Claims 25-29, 31, and 35-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-20 of U.S. Patent No. 11,771,775 (Pat ‘775) in view of Van Berkel et al. (supra) and Palanca-Wessels et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other.
Pat ‘775 claims anti-CD19 ADCs comprising an anti-CD19 antibody and the ConjE PBD conjugate (claim 1):
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Pat ‘775 additionally claims the anti-CD19 antibody comprises the VH of SEQ ID NO: 2 and the VL of SEQ ID NO: 8 (claim 1). SEQ ID NO: 2 of Pat ‘775 is 100% identical SEQ ID NO: 2:
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SEQ ID NO: 8 of Pat ‘775 is 100% identical with instant SEQ ID NO: 8:
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Pat ‘775 additionally claims methods of treating NHL comprising administration of the anti-CD19 ADC (claims 1, 6, and 7).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘775 in view of Van Berkel et al. and Palanca-Wessels et al. for the same reasons discussed for Pat ‘414 supra, especially in absence of evidence to the contrary.
Claims 25-29, 31, and 35-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-8 of U.S. Patent No. 10,646,584 (Pat ‘584) in view of Van Berkel et al. (supra) and Palanca-Wessels et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other.
Pat ‘584 claims ADCs comprising an cell-binding target and the ConjB PBD conjugate (claim 1):
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Pat ‘584 additionally claims the ADC comprises an anti-CD19 antibody (claims 4 and 5). Pat ‘584 additionally claims methods of treating cancer comprising administration of the ADC (claims 1 and 8).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘584 in view of Van Berkel et al. and Palanca-Wessels et al. for the same reasons discussed for Pat ‘414 supra, especially in absence of evidence to the contrary.
Claims 25-29, 31, and 35-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-15 of U.S. Patent No. 12,121,590 (Pat ‘590) in view of Van Berkel et al. (supra) and Palanca-Wessels et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other.
Pat ‘590 claims ADCs comprising a cell-binding target and the ConjB PBD conjugate (claim 1):
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Pat ‘590 additionally claims the ADC comprises an anti-CD19 antibody (claims 6 and 7). Pat ‘590 additionally claims methods of treating cancer comprising administration of the ADC (claims 2 and 12-14).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘590 in view of Van Berkel et al. and Palanca-Wessels et al. for the same reasons discussed for Pat ‘414 supra, especially in absence of evidence to the contrary.
Claims 25-29, 31, and 35-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-16 of U.S. Patent No. 11,318,211 (Pat ‘211) in view of Van Berkel et al. (supra) and Palanca-Wessels et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other.
Pat ‘211 claims methods of treating NHL comprising administration ADCs comprising a cell-binding target and the following PBD conjugate (claim 1):
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Pat ‘211 additionally claims the ADC comprises an anti-CD19 antibody (claim 1). Pat ‘211 additionally claims the anti-CD19 antibody comprises the VH of SEQ ID NO: 2 and the VL of SEQ ID NO: 8 (claim 1). SEQ ID NO: 2 of Pat ‘211 is 100% identical with instant SEQ ID NO: 2:
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SEQ ID NO: 8 of Pat ‘211 is 100% identical with instant SEQ ID NO: 8:
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The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘211 in view of Van Berkel et al. and Palanca-Wessels et al. for the same reasons discussed for Pat ‘414 supra, especially in absence of evidence to the contrary.
Claims 25-29, 31, and 35-37 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 11,938,192 (Pat ‘192) in view of Van Berkel et al. (supra) and Palanca-Wessels et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other.
Pat ‘192 claims methods of treating proliferative diseases comprising administration ADCs comprising a cell-binding target and the following PBD conjugate (claims 1 and 4):
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Pat ‘192 additionally claims the ADC comprises an anti-CD19 antibody (claim 4). Pat ‘192 additionally claims the anti-CD19 antibody comprises the VH of SEQ ID NO: 2 and the VL of SEQ ID NO: 8 (claim 4). SEQ ID NO: 2 of Pat ‘192 is 100% identical with instant SEQ ID NO: 2:
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SEQ ID NO: 8 of Pat ‘192 is 100% identical with instant SEQ ID NO: 8:
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The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by Pat ‘192 in view of Van Berkel et al. and Palanca-Wessels et al. for the same reasons discussed for Pat ‘414 supra, especially in absence of evidence to the contrary.
Claims 25-29, 31, and 35-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 50, 57-60, 62, and 64-66 of copending Application No. 17/819,185 (App ‘185) in view of Van Berkel et al. (supra) and Palanca-Wessels et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other.
App ‘185 claims methods of treating DLBCL (a NHL) comprising administration of ADCx19 (claim 50) The instant specification is used to determine the metes and bounds of the structure of ADCx19 (pg. 17):
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SEQ ID NO: 2 of App ‘185 is 100% identical with instant SEQ ID NO: 2:
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SEQ ID NO: 8 of App ‘185 is 100% identical with instant SEQ ID NO: 8:
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The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘185 in view of Van Berkel et al. and Palanca-Wessels et al. for the same reasons discussed for Pat ‘414 supra, especially in absence of evidence to the contrary. This is a provisional double patenting rejection.
Claims 25-29, 31, and 35-37 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 50, 57-60, 62, and 64-66 of copending Application No. 17/617,875 (App ‘875) in view of Van Berkel et al. (supra) and Palanca-Wessels et al. (supra). Although the claims at issue are not identical, they are not patentably distinct from each other.
App ‘875 claims methods of treating cancer comprising administration of loncastuximab tesirine (i.e., the ADC of instant claim 27; App ‘875 claim 41), including NHL (claim 61).
The invention encompassed by the instant claims is a prima facie obvious variant of the invention claimed by App ‘875 in view of Van Berkel et al. and Palanca-Wessels et al. for the same reasons discussed for Pat ‘414 supra, especially in absence of evidence to the contrary. This is a provisional double patenting rejection.
Conclusion
No claim is allowed.
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/ALEC JON PETERS/Examiner, Art Unit 1641
/MISOOK YU/Supervisory Patent Examiner, Art Unit 1641
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