DETAILED ACTION
This office action is in response to applicant’s filing dated September 17, 2025.
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 .
Status of Claims
Claims 1-20 are pending in the instant application. Acknowledgement is made of Applicant's remarks and amendments filed February 28, 2025. Acknowledgement is made of Applicant’s amendment of claim 1.
Applicants elected without traverse Group I, drawn to an ester-linked statin derivative of formula (FIa) as the elected invention and Compound (FId) also referred to as Compound 8 (DZ1-SIM):
PNG
media_image1.png
313
957
media_image1.png
Greyscale
as the single disclosed compound of Formula (FIa) species in the reply filed on November 14, 2023. The requirement is still deemed proper. Claims 9-20 remain withdrawn.
Claims 1-8 are presently under examination as they relate to the elected species: Compound (FId):
PNG
media_image1.png
313
957
media_image1.png
Greyscale
and a compound.
Priority
The present application is a CON of US Application No. 16/925,582 filed on July 10, 2020, which claims benefit of US Provisional Application Nos. 62/873,277 and 62/873,293 filed on July 12, 2019.
Objections and/or Rejections and Response to Arguments
Rejections and/or objections not reiterated from previous office actions are hereby withdrawn. The following rejections and/or objections are either reiterated (Maintained Objections and/or Rejections) or newly applied (New Objections and/or Rejections, Necessitated by Amendment or New Objections and/or Rejections, NOT Necessitated by Amendment). They constitute the complete set presently being applied to the instant application.
Maintained Objections and/or Rejections
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 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 1-8 are rejected under 35 U.S.C. 103 as being unpatentable over Yin et al (WO 2018/075994 A1, published April 26, 2018, cited in a previous Office Action).
Regarding claims 1-7, Yin teaches a sensitizer compound which is a DZ-DRG amide or ester conjugate wherein a DZ-residue of formula (FI) via an amide or ester bond is linked to a drug (DRG) wherein the conjugated drug (DRG is simvastatin (claim 1):
PNG
media_image2.png
362
1026
media_image2.png
Greyscale
Regarding claim 8, Yin teaches a pharmaceutical composition comprising a sensitizer compound which is DZ-DRG amide or ester conjugate and at least one pharmaceutically acceptable carrier, wherein a CA-residue of Formula FI, via an amide or ester bond is linked to the residue of a DRUG; wherein the conjugated DRG of the sensitizer is simvastatin (SIM) [0016].
Moreover, Yin teaches a sensitizer Compound 6 ([0175] Scheme 2):
PNG
media_image3.png
288
663
media_image3.png
Greyscale
Compound 6 differs from the instantly elected compound in the positions denoted by the arrows labeled A and B. In particular, the DZ residue of Compound 6 is linked to the simvastatin residue with a propylene (A) amide (B) linker, while the DZ residue of the instant claims is linked to the simvastatin residue with an ethylene ester linker. With regard to the ester vs amide linkage at position B, Yin contemplates the use of either bond to form conjugate compounds [0011]. With regard to the ethylene vs propylene linker, compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978). Moreover, MPEP 2143.I.B. states:
It should be noted that the lead compound cases do not stand for the proposition that identification of a single lead compound is necessary in every obviousness rejection of a chemical compound. For example, one might envision a suggestion in the prior art to formulate a compound having certain structurally defined moieties, or moieties with certain properties. If a person of ordinary skill would have known how to synthesize such a compound, and the structural and/or functional result could reasonably have been predicted, then a prima facie case of obviousness of the claimed chemical compound might exist even without identification a particular lead compound. As a second example, it could be possible to view a claimed compound as consisting of two known compounds attached via a chemical linker. The claimed compound might properly be found to have been obvious if there would have been a reason to link the two, if one of ordinary skill would have known how to do so, and if the resulting compound would have been the predictable result of the linkage procedure.
In the instant case, as taught by Yin conjugate compounds comprising a DZ-residue and a simvastatin residue was known in the art (i.e., a compound comprising two known compounds DZ and simvastatin attached via a chemical linker). Thus, it was known in the art to link these two compounds and it would be obvious to utilize known linkage procedures to arrive at the instantly elected compound with a reasonable expectation of success.
Taken together, all this would result in the compounds of claims 1-8 with a reasonable expectation of success.
Response to Arguments
Applicant argues:
Any modification of a moiety within a compound must be evaluated in the context of the compound as a whole. One of ordinary skill in the art would not assume that replacing one linkage at a particular position could be extrapolated to a different linkage at another position. Furthermore, Compound 6 is amenable to countless modifications-for example, at various ring positions or through alternative linkers-resulting in millions of potential analogs. One of ordinary skill in the art would not have singled out the particular amide linkage for modification with a reasonable expectation of success. The ester linkage and the amide linkage are directed to the particular side chain of the DZ dye moiety at position C, not anywhere in any linker. The amide or ester linkage is specifically directed to the side chain of the DZ moiety. There is no indication that other linkages, such as carbamates or amides at different positions, can be replaced with an ester. One of ordinary skill in the art would not have assumed the ester replacement at any position of a linker.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
The Examiner acknowledges that Yin does not explicitly teach that the DZ residue of the instant claims is linked to the simvastatin residue with an ethylene ester linker. However, as set forth above, Yin teaches structurally similar compounds comprising a structurally similar DZ residue linked to a simvastatin residue with a linker and that amide and ester linkers are alternatively useful for producing DZ-simvastatin conjugate drugs. As set forth above, with regard to the ester vs amide linkage at position B, Yin contemplates the use of either bond to form conjugate compounds. The Examiner notes that the linker is attached at two positions, one to the DZ and the other to the simvastatin. Yin teaches simvastatin can be attached via an amide or ester linkage [0012]. A skilled artisan would have easily envisaged the use of either an amide or ester linker to conjugate the simvastatin directly to the DZ-residue or to the linker between the DZ-residue and the simvastatin since Yin teaches conjugating simvastatin via either an amide or ester linkage. With regard to the ethylene vs propylene linker, compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978).
Moreover, as set forth above, it could be possible to view a claimed compound as consisting of two known compounds attached via a chemical linker. The claimed compound might properly be found to have been obvious if there would have been a reason to link the two, if one of ordinary skill would have known how to do so, and if the resulting compound would have been the predictable result of the linkage procedure. In the instant case, as taught by Yin conjugate compounds comprising a DZ-residue and a simvastatin residue was known in the art (i.e., a compound comprising two known compounds DZ and simvastatin attached via a chemical linker). Thus, it was known in the art to link these two compounds and it would be obvious to utilize known linkage procedures to arrive at the instantly elected compound with a reasonable expectation of success.
Applicant argues:
Compound 8 of Yin can be modified in numerous ways and one of ordinary skill in the art would not have singled out the particular amide linkage for modification with a reasonable expectation of success. Numerous linkers containing rings, peptides, or amides have been reported in literature. Even the distant amide moiety can be replaced with other components such as carbamate (see DZ-CIS amide and DZ-ART amide illustrated above), carbonate, ether, etc. Hundreds of thousands of compounds will arise but none of them is relevant to the claimed invention. Even if one were to attempt all possible modifications, no reasonable expectation of success would have existed. Given the vast number of possible structural modifications available in the DZ dye scaffold, there was no reasoned basis for one of ordinary skill in the art to single out the distant amide linkage for replacement with an ester. Absent any motivation to pursue this particular substitution, and in light of the inherent unpredictability of how such a change would affect compound behavior, there could have been no reasonable expectation of success.
Examiner's response:
The above argument has been carefully considered and has not been found persuasive.
As set forth above, Yin teaches structurally similar compounds comprising a structurally similar DZ residue linked to a simvastatin residue with a linker and that amide and ester linkers are alternatively useful for producing DZ-simvastatin conjugate drugs. As set forth above, with regard to the ester vs amide linkage at position B, Yin contemplates the use of either bond to form conjugate compounds. The Examiner notes that the linker is attached at two positions, one to the DZ and the other to the simvastatin. Yin teaches simvastatin can be attached via an amide or ester linkage [0012]. A skilled artisan would have easily envisaged the use of either an amide or ester linker to conjugate the simvastatin directly to the DZ-residue or to the linker between the DZ-residue and the simvastatin, since Yin teaches conjugating simvastatin via either an amide or ester linkage. With regard to the ethylene vs propylene linker, compounds which are homologs (compounds differing regularly by the successive addition of the same chemical group, e.g., by -CH2- groups) are generally of sufficiently close structural similarity that there is a presumed expectation that such compounds possess similar properties. In re Wilder, 563 F.2d 457, 195 USPQ 426 (CCPA 1977). See also In re May, 574 F.2d 1082, 197 USPQ 601 (CCPA 1978).
Moreover, as set forth above, it could be possible to view a claimed compound as consisting of two known compounds attached via a chemical linker. The claimed compound might properly be found to have been obvious if there would have been a reason to link the two, if one of ordinary skill would have known how to do so, and if the resulting compound would have been the predictable result of the linkage procedure. In the instant case, as taught by Yin conjugate compounds comprising a DZ-residue and a simvastatin residue was known in the art (i.e., a compound comprising two known compounds DZ and simvastatin attached via a chemical linker). Thus, it was known in the art to link these two compounds and it would be obvious to utilize known linkage procedures to arrive at the instantly elected compound with a reasonable expectation of success.
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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The 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/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-21 of U.S. Patent No. 11,878,000. Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims are directed to an ester-linked statin derivative of formula (FIa):
PNG
media_image4.png
279
749
media_image4.png
Greyscale
The previously granted claims are directed to a method of sensitizing cancer comprising administering a sensitizer compound wherein the sensitizer compound is a DA1-drug amide or ester conjugate (claim 1):
PNG
media_image5.png
420
363
media_image5.png
Greyscale
wherein the drug is a statin (claim 2). MPEP 2143.I.B. states:
It could be possible to view a claimed compound as consisting of two known compounds attached via a chemical linker. The claimed compound might properly be found to have been obvious if there would have been a reason to link the two, if one of ordinary skill would have known how to do so, and if the resulting compound would have been the predictable result of the linkage procedure. In the instant case, the compound of the copending claims comprise a DZ-residue and a statin residue (i.e., a compound comprising two known compounds DZ and statin attached via a chemical linker). Thus, it was known in the art to link these two compounds and it would be obvious to utilize known linkage procedures to arrive at a compound of the instant claims with a reasonable expectation of success.
Claims 1-8 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-19 of U.S. Patent No. 12,121,510 B2. Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims are directed to an ester-linked statin derivative of formula (FIa).
The previously allowed claims are directed to a sensitizer compound which is a DZ-DRG amide or ester conjugate of formula (FI) or (FII):
PNG
media_image5.png
420
363
media_image5.png
Greyscale
wherein the conjugated drug is a statin (claim 1).
MPEP 2143.I.B. states:
It could be possible to view a claimed compound as consisting of two known compounds attached via a chemical linker. The claimed compound might properly be found to have been obvious if there would have been a reason to link the two, if one of ordinary skill would have known how to do so, and if the resulting compound would have been the predictable result of the linkage procedure. In the instant case, the compound of the copending claims comprise a DZ-residue and a statin residue (i.e., a compound comprising two known compounds DZ and statin attached via a chemical linker). Thus, it was known in the art to link these two compounds and it would be obvious to utilize known linkage procedures to arrive at a compound of the instant claims with a reasonable expectation of success.
Claims 1-8 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 29 and 30 of copending Application No. 16/343,732 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because:
The instant claims are directed to an ester-linked statin derivative of formula (FIa).
The copending claims are directed to a dye-therapeutic moiety conjugate:
PNG
media_image6.png
281
730
media_image6.png
Greyscale
The compound of the copending compound is a compound of formula (FIa) conjugated to simvastatin.
MPEP 2143.I.B. states:
It could be possible to view a claimed compound as consisting of two known compounds attached via a chemical linker. The claimed compound might properly be found to have been obvious if there would have been a reason to link the two, if one of ordinary skill would have known how to do so, and if the resulting compound would have been the predictable result of the linkage procedure. In the instant case, the compound of the copending claims comprise a DZ-residue and a simvastatin residue (i.e., a compound comprising two known compounds DZ and simvastatin attached via a chemical linker). Thus, it was known in the art to link these two compounds and it would be obvious to utilize known linkage procedures to arrive at a compound of the instant claims with a reasonable expectation of success.
This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Response to Arguments
Applicant has not set forth the alleged errors regarding the merits of these rejections. Therefore, the rejections are maintained for the reasons set forth on the record.
Conclusion
Claims 1-8 are rejected.
No claim is allowed.
THIS ACTION IS MADE FINAL. 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 RAYNA B RODRIGUEZ whose telephone number is (571)272-7088. The examiner can normally be reached 8am-5:00pm, Monday - Thursday.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Amy L Clark can be reached at 571-272-1310. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/Rayna Rodriguez/ Primary Examiner, Art Unit 1628