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 .
Amendment after Non-final office action filed on March 31, 2026 is acknowledged.
Claims 32, 36-51 and 53 have been cancelled.
Claims 31, 33-35, 52 and 54 are pending in this application.
Applicant elected without traverse of Group 1 (now claims 31, 33-35 and 52) and elected plitidepsin as the species of a fully defined compound of formula I, and rheumatoid arthritis as the species of an autoimmune condition in the reply filed on September 18, 2025. Restriction was deemed to be proper and was made FINAL in the previous office action. Claim 54 remains withdrawn from consideration pursuant to 37 CFR 1.142(b), as being drawn to nonelected invention, there being no allowable generic or linking claim. Claims 31, 33-35 and 52 are examined on the merits in this office action.
This application contains claim 54 drawn to invention nonelected in the response filed on 9/18/2025. A complete reply to the final rejection must include cancellation of nonelected claims or other appropriate action (37 CFR 1.144). See MPEP § 821.01.
Withdrawn Objections and Rejections
Objection to the abstract is hereby withdrawn in view of Applicant’s amendment to the abstract.
Objection to the drawings is hereby withdrawn in view of Applicant filing replacement sheet.
Objection to claim 40 is hereby withdrawn in view of Applicant’s cancellation of the claim.
Rejection of claims 32-38, 40-41, 44, 46, 48, 50 and 52-53 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, is hereby withdrawn in view of Applicant’s amendment to the claims.
Rejection of claim 31 under 35 U.S.C. 102(a)(1) as being anticipated by Rinehart et al (US Patent No. 6156724, cited in the previous office action), is hereby withdrawn in view of Applicant’s amendment to the claim.
Please note, the specification has not been checked to the extent necessary to determine the presence of all possible error. Applicant's cooperation is required in correcting any errors of which applicant may become aware in the specification. MPEP § 608.01.
Maintained and Revised Rejections
35 U.S.C. 102
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 the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claim(s) 31, 33-35 and 52 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Nixon et al (US 2019/0192682, cited in the previous office action) or Nixon et al (US 2019/0328901, cited in the previous office action), as evidenced by Trinidad-Calderon et al (Molecules, 2023, 28(670): 1-30, cited in the previous office action). The rejection is maintained and revised in view of Applicant’s amendment to the claims.
Nixon et al teach “additional cytotoxins that can be conjugated to antibodies, antigen-binding fragments thereof, and ligands that recognize and bind CD45…for use in directly treating cancer, autoimmune condition, or for conditioning a patient…dehydrodidemnin B…” (see paragraph [0579] for ‘682 and paragraph [0577] for ‘901). As evidenced by Trinidad-Calderon et al., dehydrodidemnin B is commonly known as plitidepsin (the elected species)…dehydrodidemnin B is recognized as a part of the latest generation of didemnins, which exert no toxicity while exhibiting enhanced therapeutic and cancer-targeting effects compared with didemnin B (see p. 5, “2.1.5. Dehydrodidemnin B”). Since Nixon et al teach that the plitidepsin compound can be conjugated to antibodies, antigen-binding fragments thereof, and ligands for use in directly treating cancer, autoimmune conditions, Nixon et al as evidenced by Trinidad-Calderon et al., teach all of the active method steps, meeting the limitation of instant claim 31. Nixon et al teach that “the method is used to treat one or more disorders, such as…systemic sclerosis, systemic lupus erythematosus, juvenile rheumatoid arthritis…an autoimmune disease, such as scleroderma, multiple sclerosis, ulcerative colitis…Type 1 diabetes…” (see paragraph [0179] of ‘682 and paragraph [0177] of ‘901). Because the Nixon et al as evidenced by Trinidad-Calderon et al teach ALL of the active method steps of instant claims, Nixon et al anticipates instant claims 31, 33-35 and 52.
Response to Applicant’s Arguments
Applicant argues that “claim 31 is amended to incorporate the limitation of claims 32 and 52. Neither claim 32 nor 52 are subject to the novelty rejection in view of Nixon. It is further noted that the therapeutic agent in Nixon is an antibody drug conjugate, which is not covered by the claimed compound. Thus, Nixon does not anticipate claim 31.”
Applicant’s arguments have been fully considered but are not found persuasive. First of all, claims 32 and 52 were not included in the rejection under 35 U.S.C. 102(a)(2) is because claims 32 and 52 depended from cancelled claim 1. Furthermore, previous claims 33-38, 40-41, 44, 46-48, 50 and 53 all depended from cancelled claim 1. That is the reason why these claims were not included in the anticipation rejection under Nixon et al as evidenced by Trinidad-Calderon et al. Thus, Applicant’s argument is moot. Because Applicant has amended claims 33-35 and 52 to depend from claim 31, these claims are now included in the rejection under 35 U.S.C. 102(a)(2). Furthermore, instant claim 31 recites, “A method of treating an autoimmune condition, wherein the method comprises administering to a patient in need thereof a compound…wherein the compound is plitidepsin…” The claim does not exclude antibody conjugated plitidepsin compounds. Therefore, the rejection is deemed to be proper and is maintained herein.
35 U.S.C. 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 text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 31, 33-35 and 52 is/are rejected under 35 U.S.C. 103 as being unpatentable over Rinehart et al (US Patent No. 6156724, cited in the previous office action), in view of Nixon et al (US 2019/0192682, cited in the previous office action) or Nixon et al (US 2019/0328901, cited in the previous office action), as evidenced by Trinidad-Calderon et al (Molecules, 2023, 28(670): 1-30, cited in the previous office action). The rejection is maintained and revised in view of Applicant’s amendment to the claims.
Rinehart et al teach treating rheumatoid arthritis with the compound Didemnin B (see column 4, lines 50-60, for example; claims 1-2).
The difference between Rinehart and instant claims is that Rinehart et al do not teach plitidepsin (also known as dehydrodidemnin B).
However, Nixon et al teach “additional cytotoxins that can be conjugated to antibodies, antigen-binding fragments thereof, and ligands that recognize and bind CD45…for use in directly treating cancer, autoimmune condition, or for conditioning a patient…dehydrodidemnin B…diaziquone, didemnin B, didox…” (see paragraph [0579] for ‘682 and paragraph [0577] for ‘901). As evidenced by Trinidad-Calderon et al., dehydrodidemnin B is commonly known as plitidepsin (the elected species)…dehydrodidemnin B is recognized as a part of the latest generation of didemnins, which exert no toxicity while exhibiting enhanced therapeutic and cancer-targeting effects compared with didemnin B (see p. 5, “2.1.5. Dehydrodidemnin B”). Nixon et al teach that “the method is used to treat one or more disorders, such as…systemic sclerosis, systemic lupus erythematosus, juvenile rheumatoid arthritis…an autoimmune disease, such as scleroderma, multiple sclerosis, ulcerative colitis…Type 1 diabetes…” (see paragraph [0179] of ‘682 and paragraph [0177] of ‘901).
Therefore, it would have been obvious to one of ordinary skill in the art to combine the teachings of Rinehart et al and Nixon et al as evidenced by Trinidad-Calderon et al since Rinehart et al and Nixon et al teach treating diseases including autoimmune disorders, such as rheumatoid arthritis, by administering didemnin B and dehydrodidemnin B (the latest generation of didemnins). One of ordinary skill in the art would be motivated to combine with a reasonable expectation of success, since Nixon et al teach that dehydrodidemnin B (additional cytotoxins) that can be conjugated to antibodies, antigen-binding fragments thereof, and ligands that recognize and bind CD45…for use in directly treating cancer, autoimmune condition. Nixon et al teach that dehydrodidemnin B (plitidepsin) is the latest generation of didemnins, which exert no toxicity while exhibiting enhanced therapeutic and cancer-targeting compared with didemnin B. Thus, one of ordinary skill in the art would have a reasonable expectation that plitidepsin (dehydrodidemnin B) that is used to treat autoimmune disease would be successful in treating rheumatoid arthritis. Therefore, the combined art is prima facie obvious over instant claims 31, 33-35 and 52.
Response to Applicant’s Arguments
Applicant argues that “claim 31 is amended to incorporate the limitation of claims 32 and 52. Neither claim 32 nor 52 are subject to this 103 rejection. Thus, the Examiner has not established a prima facie case of obviousness.” . Applicant further argues that “Rinehart describes that didemnins have immunomodulatory properties…That is, Rinehart describes that didemnins may be both immune-stimulants or immune-inhibitors. Rinehart describes 42 different didemnin derivatives and assays the immunosuppressive activity of these derivatives using the mixed lymphocyte reaction (MLR) assay.” Applicant argues:
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Applicant further argues that
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. Applicant argues that “Nixon provides no experimental data relating to the successful preparation or therapeutic efficacy of an antibody-drug conjugate comprising plitidepsin.” Applicant argues that “there is no mention or suggestion in Nixon that plitidepsin could be used as a non-conjugated molecule to treat autoimmune disease. On the contrary, Nixon confirms the suggestion from Rinehart that didemnins are cytotoxic.”
Applicant’s arguments have been fully considered but are not found persuasive. First of all, claims 32 and 52 were not included in the rejection under 35 U.S.C. 103 is because claims 32 and 52 depended from cancelled claim 1. Furthermore, previous claims 33-38, 40-41, 44, 46-48, 50 and 53 all depended from cancelled claim 1. That is the reason why these claims were not included in the obviousness rejection under Rinehart et al in view of Nixon et al as evidenced by Trinidad-Calderon et al. Thus, Applicant’s argument is moot. Because Applicant has amended claims 33-35 and 52 to depend from claim 31, these claims are now included in the rejection under 35 U.S.C. 103. In regard to the Trinidad-Calderon et al reference, this reference was used as an evidentiary reference, and not a prior art reference. Trinidad-Calderon et al reference was used to provide evidence that dehydrodidemnin B is also known as plitidepsin. Nixon et al names the compound as dehydrodidemnin B. The Examiner has used the Trinidad-Calderon et al to provide evidence that the compound named in Nixon et al is the same compound plitidepsin.
It is further noted that references cited to show a universal fact need not be available as prior art before applicant’s filing date. See MPEP §2124. Therefore, Applicant’s argument is moot.
In regard to Applicant’s argument that Nixon et al teach conjugates and not plitidepsin alone, Rinehart et al teach the treatment of rheumatoid arthritis by administering didemnin B (again, please see column 4, lines 50-60, claims 1-2). As Applicant has indicated above, Rinehart describes 42 different didemnin derivatives. Therefore, one of ordinary skill in the art would be motivated to try the plitidepsin alone, since the Nixon et al teach that dehydrodidemnin B is recognized as part of the latest generation of didemnins, which exert no toxicity while exhibiting enhanced therapeutic effect compared with didemnin B. Therefore, one of ordinary skill in the art would be motivated to use the plitidepsin to treat autoimmune diseases, such as rheumatoid arthritis, since plitidepsin would be less toxic and show enhanced effect compared to didemnin B.
Furthermore, instant claim 31 recites, “A method of treating an autoimmune condition, wherein the method comprises administering to a patient in need thereof a compound…wherein the compound is plitidepsin…” The claim does not exclude antibody conjugated plitidepsin compounds. Therefore, the rejection is deemed to be proper and is maintained herein.
Applications and patents are relevant as prior art for all they contain. "The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art, including nonpreferred embodiments. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989).
Moreover, Examiner reminds Applicant that applications and patents are relevant as prior art for all they contain. "The use of patents as references is not limited to what the patentees describe as their own inventions or to the problems with which they are concerned. They are part of the literature of the art, relevant for all they contain." In re Heck, 699 F.2d 1331, 1332-33, 216 USPQ 1038, 1039 (Fed. Cir. 1983). A reference may be relied upon for all that it would have reasonably suggested to one having ordinary skill the art. Merck & Co. v. Biocraft Laboratories, 874 F.2d 804, 10 USPQ2d 1843 (Fed. Cir.), cert. denied, 493 U.S. 975 (1989).
The U.S. Federal Circuit has explicitly stated that in order to make a prima facie case of obviousness, the suggestion and motivation to combine the references need not be explicitly stated in the text of the references. In DyStar Textilfarben GmbH & Co. Deutschland KG v. C.H. Patrick Co., 80 USPQ2d 1641 (Fed. Cir. 2006), the Court writes, “the suggestion test is not a rigid categorical rule. The motivation need not be found in the references sought to be combined, but may be found in any number of sources, including common knowledge, the prior art as a whole, or the nature of the problem itself. In re Dembiczak, 175 F.3d 994, 999 [50 USPQ2d 1614] (Fed. Cir. 1999). As we explained in Motorola, Inc. v. Interdigital Tech. Corp., 121 F.3d 1461, 1472 [43 USPQ2d 1481] (Fed. Cir. 1997), ‘there is no requirement that the prior art contain an express suggestion to combine known elements to achieve the claimed invention. Rather, the suggestion to combine may come from the prior art, as filtered through the knowledge of one skilled in the art.’” See Dystar at 1645. “Our suggestion test is in actuality quite flexible and not only permits, but requires, consideration of common knowledge and common sense.” See Dystar at 1650. See also In re Fout, 675 F.2d 297, 301 (CCPA 1982) (“Express suggestion to substitute one equivalent for another need not be present to render such substitution obvious.”).
The test for obviousness is not whether the features of a secondary reference may be bodily incorporated into the structure of the primary reference; nor is it that the claimed invention must be expressly suggested in any one or all of the references. Rather, the test is what the combined teachings of the references would have suggested to those of ordinary skill in the art. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981).
Additionally, Rinehart et al and Nixon et al teach autoimmune disorders that include rheumatoid arthritis, SLE, MS, scleroderma and type 1 diabetes. Thus, the symptoms will be the same due to the same patient populations.
Therefore, the rejection is deemed to be proper and is maintained herein.
Please note: Applicant appears to be arguing that Rinehart et al teach the plitidepsin (please see Applicant’s arguments).
New Rejection
35 U.S.C. 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 52 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. 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.
Claim 52 recites, “The method of claim 31, wherein the compound is plitidepsin.” Claim 52 depends from claim 31. Claim 31 recites, “A method of treating an autoimmune condition…wherein autoimmune condition is caused by the activation of one or more Toll-like receptor (TLR), and wherein the compound is plitidepsin or a pharmaceutically acceptable salt or stereoisomer thereof.” Since claim 31 now recites that the compound is plitidepsin or a pharmaceutically acceptable salt or stereoisomer thereof, claim 52 does not further limit instant claim 31.
CONCLUSION
No claim is allowed.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JULIE HA whose telephone number is (571)272-5982. The examiner can normally be reached Monday-Thursday 5:00 am- 6:30 pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, LIANKO GARYU can be reached at 571-270-7367. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/JULIE HA/Primary Examiner, Art Unit 1654
9/7/2026
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