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 .
DETAILED ACTION
Applicant’s election without traverse of species: 1) peripheral blood Tregs; 2) a non-hematologic cancer, in the reply filed on February 27, 2026 is acknowledged.
Claims 2, 5-7, 11, 13, 14, 18, 27, 29, 31, 32, 48, and 68-74 are pending.
Claims 5 and 32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions or species, there being no allowable generic or linking claim.
Claims 2, 6, 7, 11, 13, 14, 18, 27, 29, 31, 48, and 68-74 are pending and under consideration.
Priority
It is acknowledged that this application is a 371 of International Patent Appl. No. PCT/US2021/061660 filed December 2, 2021, which claims the benefit of priority to U.S. Provisional Patent Appl. No. 63/121,044 filed December 3, 2020. The priority date has been established as December 3, 2020.
Information Disclosure Statement
The Information Disclosure Statement filed on 11/06/2024 has been considered and entered by examiner.
Claim Rejections - 35 USC § 112
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 2, 6, 7, 11, 14, 18, 27, 29, 31, 48, and 68-74 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.
The term “a camptothecin or a functional analog thereof” in claim 2 renders the claim indefinite. The term “functional analog” is not defined by the claim, 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. A functional analog of camptothecin can be any compound that performs a function or produces an effect the same as camptothecin, without necessarily sharing the same structure or composition. For example, camptothecin is an anti-tumor agent. Thus, a functional analog would encompass all anti-tumor agents which may or may not be related to camptothecin.
Section 2171 of the M.P.E.P. states
Two separate requirements are set forth in 35 U.S.C. 112(b) and pre-AIA 35 U.S.C. 112, second paragraph, namely that:
(A) the claims must set forth the subject matter that the inventor or a joint inventor regards as the invention; and
(B) the claims must particularly point out and distinctly define the metes and bounds of the subject matter to be protected by the patent grant.
The first requirement is a subjective one because it is dependent on what the inventor or a joint inventor for a patent regards as his or her invention. Note that although pre-AIA 35 U.S.C. 112, second paragraph, uses the phrase "which applicant regards as his invention," pre-AIA 37 CFR 1.41(a) provides that a patent is applied for in the name or names of the actual inventor or inventors.
The second requirement is an objective one because it is not dependent on the views of applicant or any particular individual, but is evaluated in the context of whether the claim is definite — i.e., whether the scope of the claim is clear to a hypothetical person possessing the ordinary level of skill in the pertinent art.
In the instant case of a functional analog of camptothecin, one of skill in the art could find representative examples in the art which have been defined in such terms, however, it is unclear at what point one of skill in the art would be infringing on the claims without limitations as to the metes and bounds of a functional analog of camptothecin.
Claims 6, 7, 11, 14, 18, 27, 29, 31, 48, and 68-74 are also rejected because these claims depend on claim 2 directly or indirectly.
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 2, 6, 7, 11, 13, 14, 18, 31, 48, and 68-74 are rejected under 35 U.S.C. 103 as being unpatentable over Heiser (Heiser et al., WO 2019/075188 A1, Publication Date: 04/18/2019, cited in IDS) in view of Jeffrey (Jeffrey et al., US 2019/0343828 A1, Publication Date: 11/14/2019, cited in IDS).
Heiser teaches that T regulatory cells (Tregs) are implicated in maintaining immune -suppressive conditions in the tumor microenvironment, abrogating cytotoxic anti-tumor immunosurveillance. Increased densities of intratumoral Tregs associated with poor clinical outcomes in a number of cancer types ([0006]). There is a considerable interest in developing cancer therapeutics that preferentially target intratumoral Tregs ([0006]).
Heiser teaches that breast, lung, and colorectal cancers showed CD30 to be among transcripts differentially upregulated compared to Tregs isolated from adjacent normal tissue ([0006]).
Heiser teaches a method of decreasing the activity of CD30+ Treg cells in a subject having cancer comprising administering to the subject an antibody-drug conjugate wherein the antibody-drug conjugate (ADC) comprises an anti-CD30 antibody or antigen-binding portion thereof conjugated to a monomethyl auristatin ([0008]). In some embodiments, decreasing the activity of CD30+ Treg cells comprises a decrease in the number of CD30+ Treg cells. In some embodiments, the number of CD30+ Treg cells is decreased relative to the number of CD30+ Treg cells in the subject prior to administration of the ADC ([0009], claims 1-3, 6).
Heiser teaches that the anti-CD30 antibody is monoclonal anti-CD30 antibody AC10, or cAC10 ([0013], claims 15 and 16). cAc10 induces growth arrest of CD30+ cell lines in vitro and has pronounced antitumor activity in xenograft models of Hodgkin disease ([0139]).
Heiser teaches that the BV (an ADC comprising the anti-CD30 antibody, see claim 23) drove a dose-dependent reduction of CD30+ Treg numbers (Fig. 3A, [0064], and Example 3).
Heiser teaches that BV reduced Treg cells and increased the CD8+ T cells to Treg ratio in a xeno-GVHD mouse model (Fig. 4, [0065], and Example 4).
Heiser teaches that single treatment with BV in patients with classical Hodgkin lymphoma reduced the number of Treg cells expressing CD30 as compared to the number of Treg cells without expressing CD30 ([0068], Fig. 7).
Taken together, Heiser teaches using an ADC comprising an anti-CD30 antibody (e.g., cAC10) and a cytotoxic agent: monomethyl auristatin (MMAE) to reduce the number of CD30+ Treg cells. However, Heiser does not teach an ADC comprising an anti-CD30 antibody (e.g., cAC10) and a cytotoxic agent: camptothecin, as instantly claimed.
Jeffrey teaches that camptothecin is a cytotoxin ([0058]), can be used to inhibit topoisomerase, kill tumor cells ([0207]).
Jeffrey teaches an antibody-camptothecin conjugate of Formula (IC) as shown below, wherein the antibody is cAC10 ([0158]-[0168]):
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Taken together, Jeffrey teaches an ADC comprising an anti-CD30 antibody and camptothecin.
Jeffrey teaches treating cancers with the ADC ([0305]-[0312]).
Jeffrey teaches the methods of making the ADCs (Examples 4-1, 4-2, 4-3). The cAC10-Ex_4-3 ADC has good anti-tumor activities (Fig. 3B, 3C and 4B).
Jeffrey teaches the anti-Ag2 ADCs which is a cAC10 ADC targeting CD30+ cells ([0499] and TABLE 1B).
Table of Sequences on page 104 of Jeffrey discloses the sequences of cAc10 antibody. The alignments shown below:
SEQ ID NO: 7 of Jeffrey vs. SEQ ID NO: 7 of the instant application:
US-16-376-302A-7
Query Match 100.0%; Score 635; Length 117;
Best Local Similarity 100.0%;
Matches 117; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 QIQLQQSGPEVVKPGASVKISCKASGYTFTDYYITWVKQKPGQGLEWIGWIYPGSGNTKY 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 QIQLQQSGPEVVKPGASVKISCKASGYTFTDYYITWVKQKPGQGLEWIGWIYPGSGNTKY 60
Qy 61 NEKFKGKATLTVDTSSSTAFMQLSSLTSEDTAVYFCANYGNYWFAYWGQGTQVTVSA 117
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 NEKFKGKATLTVDTSSSTAFMQLSSLTSEDTAVYFCANYGNYWFAYWGQGTQVTVSA 117
SEQ ID NO: 8 of Jeffrey vs. SEQ ID NO: 8 of the instant application:
US-16-376-302A-8
Query Match 100.0%; Score 587; Length 111;
Best Local Similarity 100.0%;
Matches 111; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 DIVLTQSPASLAVSLGQRATISCKASQSVDFDGDSYMNWYQQKPGQPPKVLIYAASNLES 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 DIVLTQSPASLAVSLGQRATISCKASQSVDFDGDSYMNWYQQKPGQPPKVLIYAASNLES 60
Qy 61 GIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPWTFGGGTKLEIK 111
|||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 GIPARFSGSGSGTDFTLNIHPVEEEDAATYYCQQSNEDPWTFGGGTKLEIK 111
SEQ ID NO: 7 comprises the amino acid sequence of SEQ ID NO: 1, 2, and 3 (underlined); SEQ ID NO: 8 comprises the amino acid sequence of SEQ ID NO: 4, 5, and 6 (underlined). Thus, cAc10 antibody reads on the antibody of instant claims 7 and 11. Jeffrey teaches cAC10 ADC shows in vivo anti-tumor activities ([0525]-[0535]).
Jeffrey teaches that anti-Ag2 ADCs (DAR=8) is effective for BV resistant cell lines ([0503] and the middle Table 2 on page 97, Fig. 5B).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of Heiser and Jeffrey to use the ADC of Jeffrey (e.g. CAC10 ADC) for decreasing the number of CD30+ Treg cells in a subject with cancers, because Heiser teaches that CD30+ Treg cells is associated with associated with poor clinical outcomes and anti-CD30 antibody-cytotoxin ADC can decrease the CD30 expressing Treg cells, and Jeffrey teach anti-CD30 antibody and camptothecin ADC show good cytotoxicity to CD30 expressing cells, is effective to cancer cells resistant to BV, and have good antitumor activity in vivo. One of ordinary skilled in the art would have a reasonable expectation that an anti-CD30 antibody and camptothecin ADC would be effective for treating cancers because it provides multi-modality therapy for cancer. The ADC can not only inhibit cancer cells expressing CD30, but also reduce Treg cell expressing CD30. The motivation would have been to develop a more powerful cancer treatment and to expand the options for cancer treatments. Given all the components are well-known in the art, one of ordinary skill in the art would have a reasonable expectation of success to reach the claimed invention.
Regarding claim 6, Heiser teaches that the CD30+ Treg cells are CD30+ inducible T regulatory cells or CD30+ peripheral Treg cells ([0011], claim 12).
Regarding claims 7 and 11, Heiser teaches that the anti-CD30 antibody is monoclonal anti-CD30 antibody AC10, or cAC10 ([0013], claims 15 and 16). cAc10 induces growth arrest of CD30+ cell lines in vitro and has pronounced antitumor activity in xenograft models of Hodgkin disease ([0139]). As set forth above, cAC10 reads on the antibodies of instant claims 7 and 11.
Regarding claim 13 and 14, Jeffrey teaches an antibody-camptothecin conjugate of Formula (IC) as shown below, wherein the antibody is cAC10 ([0158]-[0168]).
Jeffrey teaches the ADC of Formula (IC) wherein y is 1 or 4 ([0161]), z is 2, 4, 8, or 12 ([0162]), and p is 8 ([0171]). Also see the bottom compound on page 73, wherein y is 1, z is 8. It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to try different configurations of y, z and p to find the best ADC and to reach the claimed invention.
Regarding claim 18, Heiser teaches that ADC can be administered by intravenous infusion ([0308]), and weight based dosage range, e.g. about 0.1 to about 2 mg/kg ([0310]), once every 3 weeks ([0314]). In addition, one of ordinary skill in the art would have known to adjust administration regimen for specific conditions through routine practice.
Regarding claim 48, Heiser teaches that breast, lung, and colorectal cancers (non-hematologic cancers) showed CD30 to be among transcripts differentially upregulated compared to Tregs isolated from adjacent normal tissue ([0006]). One of ordinary skilled in the art would have had a reasonable expectation of success that the anti-CD30 antibody and camptothecin would be able to reduce the CD30+ Treg cells in these cancers, because the ADC shows cytotoxicity to CD30 expressing cells.
Regarding claims 68-74, the limitations recited by these claims are merely intended results of the method steps positively recited. The court noted (quoting Minton v. Nat'/ Ass'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited."' Id. Therefore, the limitation are given no weight.
Claim 27 and 29 are rejected under 35 U.S.C. 103 as being unpatentable over Heiser (Heiser et al., WO 2019/075188 A1, Publication Date: 04/18/2019, cited in IDS) in view of Jeffrey (Jeffrey et al., US 2019/0343828 A1, Publication Date: 11/14/2019, cited in IDS), as applied to claims 2, 6, 7, 11, 13, 14, 18, 31, 48, and 68-74 above, and further in view of Zhao (Zhao et al., Molecular Cancer Therapeutics, 16(9): 1866-1876, Publication Date: September, 2017) and Caselli (Caselli et al., Biologics: Targets and Therapy, (2016), 17-22, Publication Date: 02/18/2016).
Heiser and Jeffrey teach the method of claim 2 as set forth above. However, Heiser and Jeffrey do not teach the method further comprising administering G-CSF such as filgrastim.
Zhao teaches that neutropenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADC). See Abstract and § Effect of ADCs on differentiating neutrophils
Caselli teaches that advances in chemotherapy and surgery allows the majority of patients to survive cancer diseases. Yet, the price may be a proportion of patients dying of complications due to treatment-induced infectious complications, such as neutropenia. Recombinant human granulocyte colony-stimulating factor (G-CSF), filgrastim, and pegylated filgrastim have been used to reduce time and degree of neutropenia (Abstract).
Caselli teaches that G-CSF promotes the prolifera-tion, differentiation, and activation of neutrophils in the bone marrow. G-CSF works by reducing the transition time from stem cell to mature neutrophil, resulting in a larger number of functional and mature circulating neutrophils (page 18, col. 1, para. 3).
Caselli teaches that filgrastim is an approved G-CSF biosimilar (Table 2).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine teachings of Heiser and Jeffrey and teachings of Zhao and Caselli to further add a step of administering G-CSF (e.g. filgrastim). Based on the teachings of Zhao, one of ordinary skill in the art would have recognized that the method of ADC treatment taught by Heiser and Jeffrey could lead in an adversary effect of neutropenia, and Caselli teaches that G-CSF (such as filgrastim, a G-CSF biosimilar) can be used to manage neutropenia. Because filgrastim is well-known in the art and has been approved, one of ordinary skill in the art would have had a reasonable expectation by administering filgrastim could help to minimize the adversary effect of neutropenia caused by the ADC treatment. The motivation would have been to develop a better treatment.
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.
U.S. Patent No. 12,194,321
Claims 2, 6, 7, 11, 18, 31, 48, and 68-74 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-43 of U.S. Patent No. 12,194,321 B2 (hereinafter Pat. 321) in view of Heiser (Heiser et al., WO 2019/075188 A1, Publication Date: 04/18/2019, cited in IDS) and Jeffrey (Jeffrey et al., US 2019/0343828 A1, Publication Date: 11/14/2019, cited in IDS).
The claims of Pat. 321 teach a camptothecin conjugate having the formula L-(Q-D)p, wherein the L is a ligand unit, wherein the ligand unit is an antibody, p is an integer ranging from 1 to 16, and wherein the Q-D is:
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304
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. (see claim 1).
The claims of Pat. 321 teach a method of treating cancer in a subject in need thereof comprising administering to the subject an effective amount of a Camptothecin Conjugate of claim 1, or a salt thereof (claim 24), wherein the cancer us selected from the group consisting of lymphomas, leukemias, and solid cancers (claim 27)..
The claims of Pat. 321 teach the camptothecin conjugate of claim 1, wherein L is an antibody bind to CD30 (claim 36); wherein the CD30 antibody is cAC10 (claim 37). As set forth above, antibody cAc10 reads on the antibodies of instant claims 7 and 11.
Taken together, the claims of Pat. 321 teach an anti-CD30 antibody and camptothecin conjugate and the method of using the ADC to treat various cancers. However, the claims of Pat. 321 do not teach the method of decreasing the number of CD30+ Treg cells with the ADC.
Heiser and Jeffrey’s teachings are described above. In particular, Heiser teaches ADCs targeting CD30 can be used to decrease the number of CD30+ Treg cells in cancer, and Jeffrey teaches that cAC10 and camptothecin ADC shows good cytotoxicity to CD30 expressing cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Pat. 321, Heiser and Jeffrey to generate the cAC10-camptothecin ADC of Pat. 321 and to use the ADC of the claims of Pat. 321 for decreasing the number of CD30+ Treg cells in a subject with cancers, because Heiser teaches that CD30+ Treg cells is associated with associated with poor clinical outcomes and anti-CD30 antibody-cytotoxin ADC can decrease the CD30 expressing Treg cells, and Jeffrey teach anti-CD30 antibody and camptothecin ADC show good cytotoxicity to CD30 expressing cells, is effective to cancer cells resistant to BV, and have good antitumor activity in vivo. One of ordinary skilled in the art would have a reasonable expectation that an anti-CD30 antibody and camptothecin ADC would be effective for treating cancers because it provides multi-modality therapy for cancer. The ADC can not only inhibit cancer cells expressing CD30, but also reduce Treg cell expressing CD30. The motivation would have been to develop a more powerful cancer treatment and to expand the options for cancer treatments. Given all the components are well-known in the art, one of ordinary skill in the art would have a reasonable expectation of success to reach the claimed invention.
Regarding claim 18, Heiser teaches that ADC can be administered by intravenous infusion ([0308]), and weight based dosage range, e.g. about 0.1 to about 2 mg/kg ([0310]), once every 3 weeks ([0314]). In addition, one of ordinary skill in the art would have known to adjust administration regimen for specific conditions through routine practice.
Regarding claim 48, Heiser teaches that breast, lung, and colorectal cancers (non-hematologic cancers) showed CD30 to be among transcripts differentially upregulated compared to Tregs isolated from adjacent normal tissue ([0006]). One of ordinary skilled in the art would have had a reasonable expectation of success that the anti-CD30 antibody and camptothecin would be able to reduce the CD30+ Treg cells in these cancers, because the ADC shows cytotoxicity to CD30 expressing cells.
Regarding claims 68-74, the limitations recited by these claims are merely intended results of the method steps positively recited. The court noted (quoting Minton v. Nat'/ Ass'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited."' Id. Therefore, the limitation are given no weight.
Claims 27 and 29 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-43 of U.S. Patent No. 12,194,321 B2 (hereinafter Pat. 321) in view of Heiser (Heiser et al., WO 2019/075188 A1, Publication Date: 04/18/2019, cited in IDS) and Jeffrey (Jeffrey et al., US 2019/0343828 A1, Publication Date: 11/14/2019, cited in IDS), as applied to claims 2, 6, 7, 11, 18, 31, 48, and 68-74 above, and further in view of Zhao (Zhao et al., Molecular Cancer Therapeutics, 16(9): 1866-1876, Publication Date: September, 2017) and Caselli (Caselli et al., Biologics: Targets and Therapy, (2016), 17-22, Publication Date: 02/18/2016).
The claims of Pat. 321, Heiser and Jeffrey teach the method of claim 2 as set forth above. However, the claims of Pat. 321, Heiser and Jeffrey do not teach the method further comprising administering G-CSF such as filgrastim.
Zhao and Caselli’s teachings are described above. In particular, Zhao teaches that neutropenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADC). Caselli teaches that recombinant human granulocyte colony-stimulating factor (G-CSF), filgrastim, and pegylated filgrastim have been used to reduce time and degree of neutropenia (Abstract).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine teachings of the claims of Pat. 321, Heiser and Jeffrey and teachings of Zhao and Caselli to further add a step of administering G-CSF (e.g. filgrastim), based on the teachings of Zhao, one of ordinary skill in the art would have recognized that the method of ADC treatment taught by the claims of Pat. 321, Heiser and Jeffrey could lead in an adversary effect of neutropenia, and Caselli teaches that G-CSF (such as filgrastim, a G-CSF biosimilar) can be used to manage neutropenia. Because filgrastim is well-known in the art, one of ordinary skill in the art would have had a reasonable expectation by administering filgrastim could help to minimize the adversary effect of neutropenia caused by the ADC treatment. The motivation would have been to develop a better treatment.
Application No. 17/766,208
Claims 2, 6, 7, 11, 18, 31, 48, and 68-74 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 7-18, 20, 21, 29-33 of copending Application No. 17/766,208 (hereinafter Appl. 208, US 2024/0277860 A1) in view of Heiser (Heiser et al., WO 2019/075188 A1, Publication Date: 04/18/2019, cited in IDS) and Jeffrey (Jeffrey et al., US 2019/0343828 A1, Publication Date: 11/14/2019, cited in IDS).
This is a provisional nonstatutory double patenting rejection.
The claims of Appl. 208 teach camptothecin conjugate having a formula (I) (claim 1), or formula (Ib) (claim 21) both of which comprise linker and a Ligand unit.
The claims of Appl. 208 teach the Ligand Unit is an antibody (claim 29), e.g. cAC10 anti-CD30 antibody (claim 31). As set forth above, antibody cAc10 reads on the antibodies of instant claims 7 and 11.
Taken together, the claims of Appl. 208 teach an anti-CD30 antibody and camptothecin conjugate
Taken together, the claims of Appl. 208 teach an anti-CD30 antibody and camptothecin conjugate. However, the claims of Appl. 208 do not teach the method of decreasing the number of CD30+ Treg cells with the ADC.
Heiser and Jeffrey’s teachings are described above. In particular, Heiser teaches ADCs targeting CD30 can be used to decrease the number of CD30+ Treg cells in cancer, and Jeffrey teaches that cAC10 and camptothecin ADC shows good cytotoxicity to CD30 expressing cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 208, Heiser and Jeffrey to generate the cAC10-camptothecin ADC of Appl. 208 and to use the ADC of the claims of Appl. 208 for decreasing the number of CD30+ Treg cells in a subject with cancers, because Heiser teaches that CD30+ Treg cells is associated with associated with poor clinical outcomes and anti-CD30 antibody-cytotoxin ADC can decrease the CD30 expressing Treg cells, and Jeffrey teach anti-CD30 antibody and camptothecin ADC show good cytotoxicity to CD30 expressing cells, is effective to cancer cells resistant to BV, and have good antitumor activity in vivo. One of ordinary skilled in the art would have a reasonable expectation that an anti-CD30 antibody and camptothecin ADC would be effective for treating cancers because it provides multi-modality therapy for cancer. The ADC can not only inhibit cancer cells expressing CD30, but also reduce Treg cell expressing CD30. The motivation would have been to develop a more powerful cancer treatment and to expand the options for cancer treatments. Given all the components are well-known in the art, one of ordinary skill in the art would have a reasonable expectation of success to reach the claimed invention.
Regarding claim 18, Heiser teaches that ADC can be administered by intravenous infusion ([0308]), and weight based dosage range, e.g. about 0.1 to about 2 mg/kg ([0310]), once every 3 weeks ([0314]). In addition, one of ordinary skill in the art would have known to adjust administration regimen for specific conditions through routine practice.
Regarding claim 48, Heiser teaches that breast, lung, and colorectal cancers (non-hematologic cancers) showed CD30 to be among transcripts differentially upregulated compared to Tregs isolated from adjacent normal tissue ([0006]). One of ordinary skilled in the art would have had a reasonable expectation of success that the anti-CD30 antibody and camptothecin would be able to reduce the CD30+ Treg cells in these cancers, because the ADC shows cytotoxicity to CD30 expressing cells.
Regarding claims 68-74, the limitations recited by these claims are merely intended results of the method steps positively recited. The court noted (quoting Minton v. Nat'/ Ass'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited."' Id. Therefore, the limitation are given no weight.
Claims 27 and 29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1, 2, 4, 7-18, 20, 21, 29-33 of copending Application No. 17/766,208 (hereinafter Appl. 208, US 2024/0277860 A1) in view of Heiser (Heiser et al., WO 2019/075188 A1, Publication Date: 04/18/2019, cited in IDS) and Jeffrey (Jeffrey et al., US 2019/0343828 A1, Publication Date: 11/14/2019, cited in IDS) as applied to claims 2, 6, 7, 11, 18, 31, 48, and 68-74 above, and further in view of Zhao (Zhao et al., Molecular Cancer Therapeutics, 16(9): 1866-1876, Publication Date: September, 2017) and Caselli (Caselli et al., Biologics: Targets and Therapy, (2016), 17-22, Publication Date: 02/18/2016).
This is a provisional nonstatutory double patenting rejection.
The claims of Appl. 208, Heiser and Jeffrey teach the method of claim 2 as set forth above. However, the claims of Appl. 208, Heiser and Jeffrey do not teach the method further comprising administering G-CSF such as filgrastim.
Zhao and Caselli’s teachings are described above. In particular, Zhao teaches that neutropenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADC). Caselli teaches that recombinant human granulocyte colony-stimulating factor (G-CSF), filgrastim, and pegylated filgrastim have been used to reduce time and degree of neutropenia (Abstract).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine teachings of the claims of Appl. 208, Heiser and Jeffrey and teachings of Zhao and Caselli to further add a step of administering G-CSF (e.g. filgrastim), based on the teachings of Zhao, one of ordinary skill in the art would have recognized that the method of ADC treatment taught by the claims of Appl. 208, Heiser and Jeffrey could lead in an adversary effect of neutropenia, and Caselli teaches that G-CSF (such as filgrastim, a G-CSF biosimilar) can be used to manage neutropenia. Because filgrastim is well-known in the art, one of ordinary skill in the art would have had a reasonable expectation by administering filgrastim could help to minimize the adversary effect of neutropenia caused by the ADC treatment. The motivation would have been to develop a better treatment.
Application No. 19/088,772
Claims 2, 6, 7, 11, 18, 31, 48, and 68-74 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 36-55 of copending Application No. 19/088,772 (hereinafter Appl. 772, US 2025/0248994 A1) in view of Heiser (Heiser et al., WO 2019/075188 A1, Publication Date: 04/18/2019, cited in IDS) and Jeffrey (Jeffrey et al., US 2019/0343828 A1, Publication Date: 11/14/2019, cited in IDS).
This is a provisional nonstatutory double patenting rejection.
The claims of Appl. 772 teach a comptothecin conjugate having the formula L-(Q-D)p, wherein L is an antibody or a fragment thereof that specifically bind to CD30; p is an integer ranging from 1 to 8; and Q-D has the formula:
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248
568
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250
302
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. See claim 1.
The claims of Appl. 772 teach the conjugate of claim 36, wherein L is cAC10 antibody (claim 41). As set forth above, antibody cAc10 reads on the antibodies of instant claims 7 and 11.
The claims of Appl. 772 teach a method of treating cancer in a subject in need thereof comprising administering to the subject an effective amount of a camptothecin conjugate of claim 36 (claim 43).
Taken together, the claims of Appl. 772 teach an anti-CD30 antibody and camptothecin conjugate and the method of using the ADC to treat various cancers. However, the claims of Appl. 772 do not teach the method of decreasing the number of CD30+ Treg cells with the ADC.
Heiser and Jeffrey’s teachings are described above. In particular, Heiser teaches ADCs targeting CD30 can be used to decrease the number of CD30+ Treg cells in cancer, and Jeffrey teaches that cAC10 and camptothecin ADC shows good cytotoxicity to CD30 expressing cells.
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine the teachings of the claims of Appl. 772, Heiser and Jeffrey to generate the cAC10-camptothecin ADC of Appl. 772 and to use the ADC of the claims of Appl. 772 for decreasing the number of CD30+ Treg cells in a subject with cancers, because Heiser teaches that CD30+ Treg cells is associated with associated with poor clinical outcomes and anti-CD30 antibody-cytotoxin ADC can decrease the CD30 expressing Treg cells, and Jeffrey teach anti-CD30 antibody and camptothecin ADC show good cytotoxicity to CD30 expressing cells, is effective to cancer cells resistant to BV, and have good antitumor activity in vivo. One of ordinary skilled in the art would have a reasonable expectation that an anti-CD30 antibody and camptothecin ADC would be effective for treating cancers because it provides multi-modality therapy for cancer. The ADC can not only inhibit cancer cells expressing CD30, but also reduce Treg cell expressing CD30. The motivation would have been to develop a more powerful cancer treatment and to expand the options for cancer treatments. Given all the components are well-known in the art, one of ordinary skill in the art would have a reasonable expectation of success to reach the claimed invention.
Regarding claim 18, Heiser teaches that ADC can be administered by intravenous infusion ([0308]), and weight based dosage range, e.g. about 0.1 to about 2 mg/kg ([0310]), once every 3 weeks ([0314]). In addition, one of ordinary skill in the art would have known to adjust administration regimen for specific conditions through routine practice.
Regarding claim 48, Heiser teaches that breast, lung, and colorectal cancers (non-hematologic cancers) showed CD30 to be among transcripts differentially upregulated compared to Tregs isolated from adjacent normal tissue ([0006]). One of ordinary skilled in the art would have had a reasonable expectation of success that the anti-CD30 antibody and camptothecin would be able to reduce the CD30+ Treg cells in these cancers, because the ADC shows cytotoxicity to CD30 expressing cells.
Regarding claims 68-74, the limitations recited by these claims are merely intended results of the method steps positively recited. The court noted (quoting Minton v. Nat'/ Ass'n of Securities Dealers, Inc., 336 F.3d 1373, 1381, 67 USPQ2d 1614, 1620 (Fed. Cir. 2003)) that a "'whereby clause in a method claim is not given weight when it simply expresses the intended result of a process step positively recited."' Id. Therefore, the limitation are given no weight.
Claims 27 and 29 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 36-55 of copending Application No. 19/088,772 (hereinafter Appl. 772, US 2025/0248994 A1) in view of Heiser (Heiser et al., WO 2019/075188 A1, Publication Date: 04/18/2019, cited in IDS) and Jeffrey (Jeffrey et al., US 2019/0343828 A1, Publication Date: 11/14/2019, cited in IDS), as applied to claims 2, 6, 7, 11, 18, 31, 48, and 68-74 above, and further in view of Zhao (Zhao et al., Molecular Cancer Therapeutics, 16(9): 1866-1876, Publication Date: September, 2017) and Caselli (Caselli et al., Biologics: Targets and Therapy, (2016), 17-22, Publication Date: 02/18/2016).
This is a provisional nonstatutory double patenting rejection.
The claims of Appl. 772, Heiser and Jeffrey teach the method of claim 2 as set forth above. However, the claims of Appl. 772, Heiser and Jeffrey do not teach the method further comprising administering G-CSF such as filgrastim.
Zhao and Caselli’s teachings are described above. In particular, Zhao teaches that neutropenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADC). Caselli teaches that recombinant human granulocyte colony-stimulating factor (G-CSF), filgrastim, and pegylated filgrastim have been used to reduce time and degree of neutropenia (Abstract).
It would have prima facie been obvious to one of ordinarily skilled in the art at the time the invention was filed to combine teachings of the claims of Appl. 772, Heiser and Jeffrey and teachings of Zhao and Caselli to further add a step of administering G-CSF (e.g. filgrastim), based on the teachings of Zhao, one of ordinary skill in the art would have recognized that the method of ADC treatment taught by the claims of Appl. 772, Heiser and Jeffrey could lead in an adversary effect of neutropenia, and Caselli teaches that G-CSF (such as filgrastim, a G-CSF biosimilar) can be used to manage neutropenia. Because filgrastim is well-known in the art, one of ordinary skill in the art would have had a reasonable expectation by administering filgrastim could help to minimize the adversary effect of neutropenia caused by the ADC treatment. The motivation would have been to develop a better treatment.
Conclusion
No claims are allowed.
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/CHENG LU/ Examiner, Art Unit 1642
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