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 .
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
Claims 1-3, 5-17, 19, 20, 34, 42, 43, and 47 are currently pending.
Title
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed.
Specification
The disclosure is objected to because of the following informalities:
Figure 1 is described in Para 147 as “a waterfall plot of best overall response in target lesions”. It is unclear what metric serves as the basis of comparison in Figure 1. Is lesion area or diameter assessed? Is fluorescence or staining used and quantitatively assessed? Clarification is required.
Claim Objections
Claim 1 is objected to because “a oxidized” should read “an oxidized”
Claim 13 and 19 are objected to because at least one immune checkpoint inhibitor (ICI) is repeated: pembrolizumab. The duplicate inhibitor must be removed. All duplicate structures should be limited to one iteration.
Appropriate correction is required.
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, 5-17, 19, 20, 34, 42, 43, and 47 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor regards as the invention.
Claim 1 recites “and carbonyl -CH2CO-R7”. It is unclear whether carbonyl is meant to be its own item or a carbonyl is attached somehow to the structure that follows.
Claim 1 recites “substituted nitro”. It is unclear what a substituted nitro is or how such a group would be achieved. A nitro is stabilized through resonance in which electrons on the N and two O atoms are exchanged
PNG
media_image1.png
122
120
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Greyscale
. Substitution disrupts the resonance structures and is not expected to occur to form a lab stable functional group.
Claims 2-3, 5-17, 19, 20, 34, 42, 43, and 47 are rejected by virtue of dependency.
Claim Rejections - 35 USC § 112(d)
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
Claim 17 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends.
Claim 17 recites “co-administering to the subject an immune checkpoint inhibitor”. Claim 1, upon which Claim 17 depends, is now amended to include the limitation of administering the Formula (I) compound “in combination with one or more” ICI. Therefore, Claim 17 no longer further limits independent Claim 1.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claims 1-3, 5-15, 17, 19, 20, 34, 42, 43, and 47 are rejected under 35 U.S.C. 103 as being unpatentable over Huang (WO2016130839, 1/13/2025 IDS) in view of Jenkins (British Journal of Cancer (2018) 118, 9–16).
Huang teaches methods of administering the elected species, plinabulin, in combination with ICI (Title). ICI subgenera include inhibitors of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, among others, and species to be used include “nivolumab…[and] ipilimumab” (Para 13-16; Para 64). Cancer species to be treated include a myriad of those claimed including lung cancer (Para 65). Specific tested combinations include plinabulin, PD-1i, and/or CTLA-4i antibodies (Para 89). Additional agents are taught to be used including taxanes and docetaxel specifically, without restriction as to the order of administration (Para 23; Para 74). Agents may be administered together or separately, one after the other (Para 54). Further therapies to be used include radiation therapy (Para 56).
Huang does not teach administering the taught combinations of plinabulin and ICI to patient identified as having innate or acquired resistance to or progression after any ICI therapy.
Jenkins teaches ICI targeting CTLA-4, PD-1, and PD-L1 is a generally effective method of treating cancer; however, natural progression and acquired resistance are still potential outcomes of treatment. Jenkins describe emerging trends in pre-clinical data to identify innate and acquired resistance in cancer patients (Abstract; Page 9, Para 2). Individual and composite biomarkers are an emergent technology for identifying potential resistances in patients (Pages 12, Left Col, Para 2 and 14).
One of skill in the art, seeking to treat a patient described in Jenkins as identified as resistant to CTLA-4, PD-1, and/or PD-L1 blockades, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or PD-L1i, among others (e.g., treating a PD-1i resistant patient with an ICI antibody of a different subgenus like a CTLA-4i). In doing so, the specific ICI resistance is circumvented and successful treatment would be expected before the effective filing date of the claimed invention. Because plinabulin interacts synergistically with such inhibitors (Huang: Para 80, 82, 86, and 89), the same artisan would seek to treat patients with progressed or resistant cancers using the prior art combinations in conjunction with additional agents and therapies and again reasonably expect success despite the specific ICI resistance.
Claim 16 is rejected under 35 U.S.C. 103 as being unpatentable over Huang and Jenkins as applied to Claims 1-3, 5-15, 17, 19, 20, 34, 42, 43, and 47 in further view of Arakawa (Journal of Thoracic Oncology Vol. 15 No. 8. 1-2).
The teachings of Huang and Jenkins are set forth above and incorporated by reference herein.
Huang does not teach the particular form of lung cancer: recurrent small cell.
Arakawa reports a case wherein NSCLC recurred as SCLC following treatment with PD-L1i, durvalumab.
One of skill in the art seeking to treat recurrent SCLC resistant to PD-L1i, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or other non-PD-L1i. In doing so, the immune resistance is circumvented and successful treatment would be expected before the effective filing date of the claimed invention. Because plinabulin interacts synergistically with such inhibitors (Huang: Para 80, 82, 86, and 89), the same artisan would seek to treat patients with progressed or resistant cancers using the prior art combinations in conjunction with additional agents and therapies and again reasonably expect success through circumventing the specific ICI resistance.
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.
PROVISIONAL:
1. Claims 1-3, 5-17, 19, 20, 34, 42, 43, and 47 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1, 6, 11-20, 25-26, 28, 30-32, and 38 of copending Application No. 17293418 (hereinafter referred to as BeyondSpring) in view of Huang (WO2016130839, 1/13/2025 IDS), Jenkins (British Journal of Cancer (2018) 118, 9–16), and Arakawa (Journal of Thoracic Oncology Vol. 15 No. 8. 1-2).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a method of treating cancer comprising administering plinabulin.
BeyondSpring does not teach a combination therapy regimen with ICI or other agents to treat ICI resistant cancer.
Huang teaches methods of administering the elected species, plinabulin, in combination with ICI (Title). ICI subgenera include inhibitors of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, among others, and species to be used include “nivolumab…[and] ipilimumab” (Para 13-16; Para 64). Cancer species to be treated include a myriad of those claimed including lung cancer (Para 65). Specific tested combinations include plinabulin, PD-1i, and/or CTLA-4i antibodies (Para 89). Additional agents are taught to be used including taxanes and docetaxel specifically, without restriction as to the order of administration (Para 23; Para 74). Agents may be administered together or separately, one after the other (Para 54). Further therapies to be used include radiation therapy (Para 56).
Huang does not teach administering the taught combinations of plinabulin and ICI to patient identified as having innate or acquired resistance to or progression after any ICI therapy.
Jenkins teaches ICI targeting CTLA-4, PD-1, and PD-L1 is a generally effective method of treating cancer; however, natural progression and acquired resistance are still potential outcomes of treatment. Jenkins describe emerging trends in pre-clinical data to identify innate and acquired resistance in cancer patients (Abstract; Page 9, Para 2). Individual and composite biomarkers are an emergent technology for identifying potential resistances in patients (Pages 12, Left Col, Para 2 and 14).
Arakawa reports a case wherein NSCLC recurred as SCLC following treatment with PD-L1i, durvalumab (whole document).
One of skill in the art, seeking to treat a patient described in Jenkins as identified as resistant to CTLA-4, PD-1, and/or PD-L1 blockades, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or PD-L1i, among others (e.g., treating a PD-1i resistant patient with an ICI antibody of a different subgenera like a CTLA-4i). In doing so, the immune resistance is circumvented and successful treatment would be expected before the effective filing date of the claimed invention. Because plinabulin interacts synergistically with such inhibitors (Huang: Para 80, 82, 86, and 89), the same artisan would seek to treat patients with progressed or resistant cancers using the agents and methods identified in BeyondSpring and Huang in conjunction with additional agents and therapies and again reasonably expect success through circumventing the specific ICI resistance.
One of skill in the art seeking to treat recurrent SCLC resistant to PD-L1i, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or other non-PD-L1i, and using the methods described in detail above for the aforementioned reasons.
Since both applications teach the administration of plinabulin for the treatment of cancer, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of BeyondSpring.
This is a provisional nonstatutory double patenting rejection.
2. Claims 1-3, 5-17, 19, 20, 34, 42, 43, and 47 are provisionally rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-18 of copending Application No. 18952618 (hereinafter referred to as BeyondSpring) in view of Huang (WO2016130839, 1/13/2025 IDS), Jenkins (British Journal of Cancer (2018) 118, 9–16), and Arakawa (Journal of Thoracic Oncology Vol. 15 No. 8. 1-2).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a method of treating cancer (NSCLC) comprising administering plinabulin and ICI.
BeyondSpring does not teach a combination therapy regimen with other agents to treat ICI resistant cancer.
Huang teaches methods of administering the elected species, plinabulin, in combination with ICI (Title). ICI subgenera include inhibitors of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, among others, and species to be used include “nivolumab…[and] ipilimumab” (Para 13-16; Para 64). Cancer species to be treated include a myriad of those claimed including lung cancer (Para 65). Specific tested combinations include plinabulin, PD-1i, and/or CTLA-4i antibodies (Para 89). Additional agents are taught to be used including taxanes and docetaxel specifically, without restriction as to the order of administration (Para 23; Para 74). Agents may be administered together or separately, one after the other (Para 54). Further therapies to be used include radiation therapy (Para 56).
Huang does not teach administering the taught combinations of plinabulin and ICI to patient identified as having innate or acquired resistance to or progression after any ICI therapy.
Jenkins teaches ICI targeting CTLA-4, PD-1, and PD-L1 is a generally effective method of treating cancer; however, natural progression and acquired resistance are still potential outcomes of treatment. Jenkins describe emerging trends in pre-clinical data to identify innate and acquired resistance in cancer patients (Abstract; Page 9, Para 2). Individual and composite biomarkers are an emergent technology for identifying potential resistances in patients (Pages 12, Left Col, Para 2 and 14).
Arakawa reports a case wherein NSCLC recurred as SCLC following treatment with PD-L1i, durvalumab (whole document).
One of skill in the art, seeking to treat a patient described in Jenkins as identified as resistant to CTLA-4, PD-1, and/or PD-L1 blockades, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or PD-L1i, among others (e.g., treating a PD-1i resistant patient with an ICI antibody of a different subgenera like a CTLA-4i). In doing so, the immune resistance is circumvented and successful treatment would be expected before the effective filing date of the claimed invention. Because plinabulin interacts synergistically with such inhibitors (Huang: Para 80, 82, 86, and 89), the same artisan would seek to treat patients with progressed or resistant cancers using the agents and methods identified in BeyondSpring and Huang in conjunction with additional agents and therapies and again reasonably expect success through circumventing the specific ICI resistance.
One of skill in the art seeking to treat recurrent SCLC resistant to PD-L1i, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or other non-PD-L1i, and using the methods described in detail above for the aforementioned reasons.
Since both applications teach the administration of plinabulin for the treatment of cancer, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of BeyondSpring.
This is a provisional nonstatutory double patenting rejection.
NONPROVISIONAL:
1. Claims 1-3, 5-15, 17, 19, 20, 34, 42, 43, and 47 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-13 of U.S. Patent No. 8618292 (hereinafter referred to as BeyondSpring) in view of Huang (WO2016130839, 1/13/2025 IDS) and Jenkins (British Journal of Cancer (2018) 118, 9–16).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a method of treating melanoma comprising administering plinabulin and ICI.
BeyondSpring does not teach a combination therapy regimen with other agents to treat ICI resistant cancer.
Huang teaches methods of administering the elected species, plinabulin, in combination with ICI (Title). ICI subgenera include inhibitors of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, among others, and species to be used include “nivolumab…[and] ipilimumab” (Para 13-16; Para 64). Specific tested combinations include plinabulin, PD-1i, and/or CTLA-4i antibodies (Para 89). Additional agents are taught to be used including taxanes and docetaxel specifically, without restriction as to the order of administration (Para 23; Para 74). Agents may be administered together or separately, one after the other (Para 54). Further therapies to be used include radiation therapy (Para 56).
Huang does not teach administering the taught combinations of plinabulin and ICI to patient identified as having innate or acquired resistance to or progression after any ICI therapy.
Jenkins teaches ICI targeting CTLA-4, PD-1, and PD-L1 is a generally effective method of treating cancer; however, natural progression and acquired resistance are still potential outcomes of treatment. Jenkins describe emerging trends in pre-clinical data to identify innate and acquired resistance in cancer patients (Abstract; Page 9, Para 2). Individual and composite biomarkers are an emergent technology for identifying potential resistances in patients (Pages 12, Left Col, Para 2 and 14).
Arakawa reports a case wherein NSCLC recurred as SCLC following treatment with PD-L1i, durvalumab (whole document).
One of skill in the art, seeking to treat a patient described in Jenkins as identified as resistant to CTLA-4, PD-1, and/or PD-L1 blockades, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or PD-L1i, among others (e.g., treating a PD-1i resistant patient with an ICI antibody of a different subgenera like a CTLA-4i). In doing so, the immune resistance is circumvented and successful treatment would be expected before the effective filing date of the claimed invention. Because plinabulin interacts synergistically with such inhibitors (Huang: Para 80, 82, 86, and 89), the same artisan would seek to treat patients with progressed or resistant cancers using the agents and methods identified in BeyondSpring and Huang in conjunction with additional agents and therapies and again reasonably expect success through circumventing the specific ICI resistance.
Since both claim sets teach a method of administering plinabulin to treat cancer, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of BeyondSpring.
2. Claims 1-3, 5-17, 19, 20, 34, 42, 43, and 47 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-49 of U.S. Patent No. 9358289 (hereinafter referred to as BeyondSpring) in view of Huang (WO2016130839, 1/13/2025 IDS), Jenkins (British Journal of Cancer (2018) 118, 9–16), and Arakawa (Journal of Thoracic Oncology Vol. 15 No. 8. 1-2).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a method of treating cancer comprising administering plinabulin and ICI.
BeyondSpring does not teach a combination therapy regimen with other agents to treat ICI resistant cancer.
Huang teaches methods of administering the elected species, plinabulin, in combination with ICI (Title). ICI subgenera include inhibitors of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, among others, and species to be used include “nivolumab…[and] ipilimumab” (Para 13-16; Para 64). Cancer species to be treated include a myriad of those claimed including lung cancer (Para 65). Specific tested combinations include plinabulin, PD-1i, and/or CTLA-4i antibodies (Para 89). Additional agents are taught to be used including taxanes and docetaxel specifically, without restriction as to the order of administration (Para 23; Para 74). Agents may be administered together or separately, one after the other (Para 54). Further therapies to be used include radiation therapy (Para 56).
Huang does not teach administering the taught combinations of plinabulin and ICI to patient identified as having innate or acquired resistance to or progression after any ICI therapy.
Jenkins teaches ICI targeting CTLA-4, PD-1, and PD-L1 is a generally effective method of treating cancer; however, natural progression and acquired resistance are still potential outcomes of treatment. Jenkins describe emerging trends in pre-clinical data to identify innate and acquired resistance in cancer patients (Abstract; Page 9, Para 2). Individual and composite biomarkers are an emergent technology for identifying potential resistances in patients (Pages 12, Left Col, Para 2 and 14).
Arakawa reports a case wherein NSCLC recurred as SCLC following treatment with PD-L1i, durvalumab (whole document).
One of skill in the art, seeking to treat a patient described in Jenkins as identified as resistant to CTLA-4, PD-1, and/or PD-L1 blockades, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or PD-L1i, among others (e.g., treating a PD-1i resistant patient with an ICI antibody of a different subgenera like a CTLA-4i). In doing so, the immune resistance is circumvented and successful treatment would be expected before the effective filing date of the claimed invention. Because plinabulin interacts synergistically with such inhibitors (Huang: Para 80, 82, 86, and 89), the same artisan would seek to treat patients with progressed or resistant cancers using the agents and methods identified in BeyondSpring and Huang in conjunction with additional agents and therapies and again reasonably expect success through circumventing the specific ICI resistance.
One of skill in the art seeking to treat recurrent SCLC resistant to PD-L1i, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or other non-PD-L1i, and using the methods described in detail above for the aforementioned reasons.
Since both claim sets teach a method of administering plinabulin to treat cancer, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of BeyondSpring.
3. Claims 1-3, 5-15, 17, 19, 20, 34, 42, 43, and 47 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-19 of U.S. Patent No. 10076518 (hereinafter referred to as BeyondSpring) in view of Huang (WO2016130839, 1/13/2025 IDS) and Jenkins (British Journal of Cancer (2018) 118, 9–16).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a method of treating brain cancer comprising administering plinabulin and ICI in combination with radiation therapy.
BeyondSpring does not teach a combination therapy regimen with other agents to treat ICI resistant cancer.
Huang teaches methods of administering the elected species, plinabulin, in combination with ICI (Title). ICI subgenera include inhibitors of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, among others, and species to be used include “nivolumab…[and] ipilimumab” (Para 13-16; Para 64). Specific tested combinations include plinabulin, PD-1i, and/or CTLA-4i antibodies (Para 89). Additional agents are taught to be used including taxanes and docetaxel specifically, without restriction as to the order of administration (Para 23; Para 74). Agents may be administered together or separately, one after the other (Para 54). Further therapies to be used include radiation therapy (Para 56).
Huang does not teach administering the taught combinations of plinabulin and ICI to patient identified as having innate or acquired resistance to or progression after any ICI therapy.
Jenkins teaches ICI targeting CTLA-4, PD-1, and PD-L1 is a generally effective method of treating cancer; however, natural progression and acquired resistance are still potential outcomes of treatment. Jenkins describe emerging trends in pre-clinical data to identify innate and acquired resistance in cancer patients (Abstract; Page 9, Para 2). Individual and composite biomarkers are an emergent technology for identifying potential resistances in patients (Pages 12, Left Col, Para 2 and 14).
Arakawa reports a case wherein NSCLC recurred as SCLC following treatment with PD-L1i, durvalumab (whole document).
One of skill in the art, seeking to treat a patient described in Jenkins as identified as resistant to CTLA-4, PD-1, and/or PD-L1 blockades, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or PD-L1i, among others (e.g., treating a PD-1i resistant patient with an ICI antibody of a different subgenera like a CTLA-4i). In doing so, the immune resistance is circumvented and successful treatment would be expected before the effective filing date of the claimed invention. Because plinabulin interacts synergistically with such inhibitors (Huang: Para 80, 82, 86, and 89), the same artisan would seek to treat patients with progressed or resistant cancers using the agents and methods identified in BeyondSpring and Huang in conjunction with additional agents and therapies and again reasonably expect success through circumventing the specific ICI resistance.
Since both claim sets teach a method of administering plinabulin to treat cancer, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of BeyondSpring.
4. Claims 1-3, 5-17, 19, 20, 34, 42, 43, and 47 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-24 of U.S. Patent No. 10238650 (hereinafter referred to as BeyondSpring) in view of Huang (WO2016130839, 1/13/2025 IDS), Jenkins (British Journal of Cancer (2018) 118, 9–16), and Arakawa (Journal of Thoracic Oncology Vol. 15 No. 8. 1-2).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a method of treating cancers comprising administering plinabulin.
BeyondSpring does not teach a combination therapy regimen with ICI or other agents to treat ICI resistant cancer.
Huang teaches methods of administering the elected species, plinabulin, in combination with ICI (Title). ICI subgenera include inhibitors of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, among others, and species to be used include “nivolumab…[and] ipilimumab” (Para 13-16; Para 64). Cancer species to be treated include a myriad of those claimed including lung cancer (Para 65). Specific tested combinations include plinabulin, PD-1i, and/or CTLA-4i antibodies (Para 89). Additional agents are taught to be used including taxanes and docetaxel specifically, without restriction as to the order of administration (Para 23; Para 74). Agents may be administered together or separately, one after the other (Para 54). Further therapies to be used include radiation therapy (Para 56).
Huang does not teach administering the taught combinations of plinabulin and ICI to patient identified as having innate or acquired resistance to or progression after any ICI therapy.
Jenkins teaches ICI targeting CTLA-4, PD-1, and PD-L1 is a generally effective method of treating cancer; however, natural progression and acquired resistance are still potential outcomes of treatment. Jenkins describe emerging trends in pre-clinical data to identify innate and acquired resistance in cancer patients (Abstract; Page 9, Para 2). Individual and composite biomarkers are an emergent technology for identifying potential resistances in patients (Pages 12, Left Col, Para 2 and 14).
Arakawa reports a case wherein NSCLC recurred as SCLC following treatment with PD-L1i, durvalumab (whole document).
One of skill in the art, seeking to treat a patient described in Jenkins as identified as resistant to CTLA-4, PD-1, and/or PD-L1 blockades, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or PD-L1i, among others (e.g., treating a PD-1i resistant patient with an ICI antibody of a different subgenera like a CTLA-4i). In doing so, the immune resistance is circumvented and successful treatment would be expected before the effective filing date of the claimed invention. Because plinabulin interacts synergistically with such inhibitors (Huang: Para 80, 82, 86, and 89), the same artisan would seek to treat patients with progressed or resistant cancers using the agents and methods identified in BeyondSpring and Huang in conjunction with additional agents and therapies and again reasonably expect success through circumventing the specific ICI resistance.
One of skill in the art seeking to treat recurrent SCLC resistant to PD-L1i, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or other non-PD-L1i, and using the methods described in detail above for the aforementioned reasons.
Since both claim sets teach a method of administering plinabulin to treat cancer, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of BeyondSpring.
5. Claims 1-3, 5-17, 19, 20, 34, 42, 43, and 47 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-20 of U.S. Patent No. 10357491 (hereinafter referred to as BeyondSpring) in view of Huang (WO2016130839, 1/13/2025 IDS) and Jenkins (British Journal of Cancer (2018) 118, 9–16).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a method of treating brain cancer comprising administering plinabulin and ICI in combination with radiation therapy.
BeyondSpring does not teach a combination therapy regimen with other agents to treat ICI resistant cancer.
Huang teaches methods of administering the elected species, plinabulin, in combination with ICI (Title). ICI subgenera include inhibitors of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, among others, and species to be used include “nivolumab…[and] ipilimumab” (Para 13-16; Para 64). Specific tested combinations include plinabulin, PD-1i, and/or CTLA-4i antibodies (Para 89). Additional agents are taught to be used including taxanes and docetaxel specifically, without restriction as to the order of administration (Para 23; Para 74). Agents may be administered together or separately, one after the other (Para 54). Further therapies to be used include radiation therapy (Para 56).
Huang does not teach administering the taught combinations of plinabulin and ICI to patient identified as having innate or acquired resistance to or progression after any ICI therapy.
Jenkins teaches ICI targeting CTLA-4, PD-1, and PD-L1 is a generally effective method of treating cancer; however, natural progression and acquired resistance are still potential outcomes of treatment. Jenkins describe emerging trends in pre-clinical data to identify innate and acquired resistance in cancer patients (Abstract; Page 9, Para 2). Individual and composite biomarkers are an emergent technology for identifying potential resistances in patients (Pages 12, Left Col, Para 2 and 14).
Arakawa reports a case wherein NSCLC recurred as SCLC following treatment with PD-L1i, durvalumab (whole document).
One of skill in the art, seeking to treat a patient described in Jenkins as identified as resistant to CTLA-4, PD-1, and/or PD-L1 blockades, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or PD-L1i, among others (e.g., treating a PD-1i resistant patient with an ICI antibody of a different subgenera like a CTLA-4i). In doing so, the immune resistance is circumvented and successful treatment would be expected before the effective filing date of the claimed invention. Because plinabulin interacts synergistically with such inhibitors (Huang: Para 80, 82, 86, and 89), the same artisan would seek to treat patients with progressed or resistant cancers using the agents and methods identified in BeyondSpring and Huang in conjunction with additional agents and therapies and again reasonably expect success through circumventing the specific ICI resistance.
Since both claim sets teach a method of administering plinabulin to treat cancer, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of BeyondSpring.
6. Claims 1-3, 5-17, 19, 20, 34, 42, 43, and 47 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 21 of U.S. Patent No. 10668063 (hereinafter referred to as BeyondSpring) in view of Huang (WO2016130839, 1/13/2025 IDS), Jenkins (British Journal of Cancer (2018) 118, 9–16), and Arakawa (Journal of Thoracic Oncology Vol. 15 No. 8. 1-2).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a method of treating cancers comprising administering plinabulin.
BeyondSpring does not teach a combination therapy regimen with ICI or other agents to treat ICI resistant cancer.
Huang teaches methods of administering the elected species, plinabulin, in combination with ICI (Title). ICI subgenera include inhibitors of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, among others, and species to be used include “nivolumab…[and] ipilimumab” (Para 13-16; Para 64). Cancer species to be treated include a myriad of those claimed including lung cancer (Para 65). Specific tested combinations include plinabulin, PD-1i, and/or CTLA-4i antibodies (Para 89). Additional agents are taught to be used including taxanes and docetaxel specifically, without restriction as to the order of administration (Para 23; Para 74). Agents may be administered together or separately, one after the other (Para 54). Further therapies to be used include radiation therapy (Para 56).
Huang does not teach administering the taught combinations of plinabulin and ICI to patient identified as having innate or acquired resistance to or progression after any ICI therapy.
Jenkins teaches ICI targeting CTLA-4, PD-1, and PD-L1 is a generally effective method of treating cancer; however, natural progression and acquired resistance are still potential outcomes of treatment. Jenkins describe emerging trends in pre-clinical data to identify innate and acquired resistance in cancer patients (Abstract; Page 9, Para 2). Individual and composite biomarkers are an emergent technology for identifying potential resistances in patients (Pages 12, Left Col, Para 2 and 14).
Arakawa reports a case wherein NSCLC recurred as SCLC following treatment with PD-L1i, durvalumab (whole document).
One of skill in the art, seeking to treat a patient described in Jenkins as identified as resistant to CTLA-4, PD-1, and/or PD-L1 blockades, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or PD-L1i, among others (e.g., treating a PD-1i resistant patient with an ICI antibody of a different subgenera like a CTLA-4i). In doing so, the immune resistance is circumvented and successful treatment would be expected before the effective filing date of the claimed invention. Because plinabulin interacts synergistically with such inhibitors (Huang: Para 80, 82, 86, and 89), the same artisan would seek to treat patients with progressed or resistant cancers using the agents and methods identified in BeyondSpring and Huang in conjunction with additional agents and therapies and again reasonably expect success through circumventing the specific ICI resistance.
One of skill in the art seeking to treat recurrent SCLC resistant to PD-L1i, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or other non-PD-L1i, and using the methods described in detail above for the aforementioned reasons.
Since both claim sets teach a method of administering plinabulin to treat cancer, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of BeyondSpring.
7. Claims 1-3, 5-17, 19, 20, 34, 42, 43, and 47 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-20 of U.S. Patent No. 11045467 (hereinafter referred to as BeyondSpring) in view of Huang (WO2016130839, 1/13/2025 IDS), Jenkins (British Journal of Cancer (2018) 118, 9–16), and Arakawa (Journal of Thoracic Oncology Vol. 15 No. 8. 1-2).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a method of treating cancers comprising administering plinabulin.
BeyondSpring does not teach a combination therapy regimen with ICI or other agents to treat ICI resistant cancer.
Huang teaches methods of administering the elected species, plinabulin, in combination with ICI (Title). ICI subgenera include inhibitors of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, among others, and species to be used include “nivolumab…[and] ipilimumab” (Para 13-16; Para 64). Cancer species to be treated include a myriad of those claimed including lung cancer (Para 65). Specific tested combinations include plinabulin, PD-1i, and/or CTLA-4i antibodies (Para 89). Additional agents are taught to be used including taxanes and docetaxel specifically, without restriction as to the order of administration (Para 23; Para 74). Agents may be administered together or separately, one after the other (Para 54). Further therapies to be used include radiation therapy (Para 56).
Huang does not teach administering the taught combinations of plinabulin and ICI to patient identified as having innate or acquired resistance to or progression after any ICI therapy.
Jenkins teaches ICI targeting CTLA-4, PD-1, and PD-L1 is a generally effective method of treating cancer; however, natural progression and acquired resistance are still potential outcomes of treatment. Jenkins describe emerging trends in pre-clinical data to identify innate and acquired resistance in cancer patients (Abstract; Page 9, Para 2). Individual and composite biomarkers are an emergent technology for identifying potential resistances in patients (Pages 12, Left Col, Para 2 and 14).
Arakawa reports a case wherein NSCLC recurred as SCLC following treatment with PD-L1i, durvalumab (whole document).
One of skill in the art, seeking to treat a patient described in Jenkins as identified as resistant to CTLA-4, PD-1, and/or PD-L1 blockades, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or PD-L1i, among others (e.g., treating a PD-1i resistant patient with an ICI antibody of a different subgenera like a CTLA-4i). In doing so, the immune resistance is circumvented and successful treatment would be expected before the effective filing date of the claimed invention. Because plinabulin interacts synergistically with such inhibitors (Huang: Para 80, 82, 86, and 89), the same artisan would seek to treat patients with progressed or resistant cancers using the agents and methods identified in BeyondSpring and Huang in conjunction with additional agents and therapies and again reasonably expect success through circumventing the specific ICI resistance.
One of skill in the art seeking to treat recurrent SCLC resistant to PD-L1i, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or other non-PD-L1i, and using the methods described in detail above for the aforementioned reasons.
Since both claim sets teach a method of administering plinabulin to treat cancer, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of BeyondSpring.
8. Claims 1-3, 5-17, 19, 20, 34, 42, 43, and 47 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-20 of U.S. Patent No. 11918574 (hereinafter referred to as BeyondSpring) in view of Huang (WO2016130839, 1/13/2025 IDS), Jenkins (British Journal of Cancer (2018) 118, 9–16), and Arakawa (Journal of Thoracic Oncology Vol. 15 No. 8. 1-2).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a method of treating cancers comprising administering plinabulin in combination with radiation therapy.
BeyondSpring does not teach a combination therapy regimen with ICI or other agents to treat ICI resistant cancer.
Huang teaches methods of administering the elected species, plinabulin, in combination with ICI (Title). ICI subgenera include inhibitors of CTLA-4, PD-1, PD-L1, PD-L2, LAG-3, among others, and species to be used include “nivolumab…[and] ipilimumab” (Para 13-16; Para 64). Cancer species to be treated include a myriad of those claimed including lung cancer (Para 65). Specific tested combinations include plinabulin, PD-1i, and/or CTLA-4i antibodies (Para 89). Additional agents are taught to be used including taxanes and docetaxel specifically, without restriction as to the order of administration (Para 23; Para 74). Agents may be administered together or separately, one after the other (Para 54). Further therapies to be used include radiation therapy (Para 56).
Huang does not teach administering the taught combinations of plinabulin and ICI to patient identified as having innate or acquired resistance to or progression after any ICI therapy.
Jenkins teaches ICI targeting CTLA-4, PD-1, and PD-L1 is a generally effective method of treating cancer; however, natural progression and acquired resistance are still potential outcomes of treatment. Jenkins describe emerging trends in pre-clinical data to identify innate and acquired resistance in cancer patients (Abstract; Page 9, Para 2). Individual and composite biomarkers are an emergent technology for identifying potential resistances in patients (Pages 12, Left Col, Para 2 and 14).
Arakawa reports a case wherein NSCLC recurred as SCLC following treatment with PD-L1i, durvalumab (whole document).
One of skill in the art, seeking to treat a patient described in Jenkins as identified as resistant to CTLA-4, PD-1, and/or PD-L1 blockades, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or PD-L1i, among others (e.g., treating a PD-1i resistant patient with an ICI antibody of a different subgenera like a CTLA-4i). In doing so, the immune resistance is circumvented and successful treatment would be expected before the effective filing date of the claimed invention. Because plinabulin interacts synergistically with such inhibitors (Huang: Para 80, 82, 86, and 89), the same artisan would seek to treat patients with progressed or resistant cancers using the agents and methods identified in BeyondSpring and Huang in conjunction with additional agents and therapies and again reasonably expect success through circumventing the specific ICI resistance.
One of skill in the art seeking to treat recurrent SCLC resistant to PD-L1i, would find it obvious to potentiate an immune response to the tumor through administering ICI which are not resisted by the patient, CTLA-4i, PD-1i, and/or other non-PD-L1i, and using the methods described in detail above for the aforementioned reasons.
Since both claim sets teach a method of administering plinabulin to treat cancer, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of BeyondSpring.
9. Claims 1-3, 5-17, 19, 20, 34, 42, 43, and 47 are rejected on the grounds of nonstatutory double patenting as being unpatentable over Claims 1-22 of U.S. Patent No. 12377094 (hereinafter referred to as BeyondSpring).
Although the claims at issue are not identical, they are not patentably distinct from each other because both applications are directed to a method of treating ICI resistant cancer (SCLC) comprising administering a combination of ICI and plinabulin with other agents (docetaxel) and radiation therapy.
Since both claim sets teach a method of administering plinabulin to treat cancer, the examiner maintains that the aforementioned claims of the instant application are substantially overlapping in scope as discussed hereinabove and are prima facie obvious over the cited claims of BeyondSpring.
Conclusion
No claim is allowable.
Inquiries
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/RICHARD GRANT PECKHAM/Examiner, Art Unit 1627
/Kortney L. Klinkel/Supervisory Patent Examiner, Art Unit 1627