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 .
Claims and Previous Objections/Rejections Status
Claims 209-234 are pending in the application.
Any objections and/or rejections from previous office actions that have not been reiterated in this office action are obviated.
Response to Arguments
Applicant's arguments filed 10/2/25 have been fully considered but they are not persuasive.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
Claim(s) 209-234 is/are rejected under 35 U.S.C. 103 as being unpatentable over Kobayashi et al. (US 8,524,239B2) in view of Chang et al. (US 2017/0021017A1) and Jain et al. (US 2013/0287688A1) and in further view of Yoon et al. (Clinc. Endosc. 2013, 43, 7-23) and Mizeret et al. (Lasers in Surgery and Medicine 19:159-167 (1996) as stated in the office action mailed 4/3/25.
Applicant asserts that the teachings in Kobayashi are different from the current claims at least because Kobayashi does not teach or suggest administering an immune checkpoint inhibitor and a conjugate comprising a IR700 linked to an anti-CD25 antibody for PIT that is administered and irradiated as presently claimed. Notably, Kobayashi does not reference an immune checkpoint inhibitor at all.
The Examiner asserts that Kobayashi was not used to teach of administering an immune checkpoint inhibitor in combination with the anti-CD25 antibody-IR700 conjugate for PIT.
The reference of Kobayashi was used to teach of the administration of an anti-CD25 antibody-IR700 conjugate for the method of killing cells via targeted PIT.
Applicant asserts that Kobayashi et al. does not teach or suggest irradiating an area near the tumor at a dose of from about 25 J cm-2 to about 400 J cm-2 or from about 25 J/cm of fiber length to about 500 J/cm of fiber length in conjunction with administration of the conjugate and the immune checkpoint inhibitor as claimed. Kobayashi mentions CD25 as a possible cell surface protein, Kobayashi does not teach or suggest targeting of an anti-CD25 conjugate to immunosuppressive cells, such as Tregs, to effect lysis and death of immunosuppressive Tregs.
The reference of Kobayashi was used to teach of the administration of the anti-CD25 antibody-IR700 conjugate for the method of killing cells via targeted PIT upon irradiation with NIR light at a dose of at least 30 J cm-2, at least 50 J cm-2, at least 100 J cm-2 or at least 500 J cm-2, etc. at a wavelength of 660-740 nm that encompasses the dose of from at or about 25 J cm-2 to at or about 400 J cm-2 at a wavelength of 600 nm to 850 nm of the instant claims.
The anti-CD25 antibodies used for targeting the tumor specific protein CD25 comprise daclizumab and basiliximab that encompass the anti-CD25 antibodies daclizumab and basiliximab of the instant claims.
Near-infrared photoimmunotherapy (NIR-PIT) is defined, as evidenced by Kobayashi et al. (Int. Immunol. (2020) Vol 33. No. 1, pp 7-15) and Mitsunaga et al. (Nat. Med. (2011) 17:1685, incorporated by reference), as a therapy that induces direct cancer killing via immunogenic cell death (ICD), thus activating the anti-cancer immune system locally in the TME (23). NIR-PIT is designed to selectively destroy target cells. The specificity comes from the mAb, which is conjugated to the photo-activating, phthalocyanine-based chemical, IRDye700DX (IR700). (p8, Design strategy of near-infrared photoimmunotherapy).
Therefore, it would have been predictable to one of ordinary skill in the art that the administration of the antibody-IR700 conjugate and the dose of NIR light of Kobayashi innately provides killing of immunosuppressive cells via PIT with a reasonable expectation of success.
The reference of Chang et al. was used to teach of treating cancer via immunotherapy upon the administration of a combination of two or more agents, such as antibody-drug conjugates (ADCs) and/or checkpoint inhibition antibodies for the advantage of inducing an immune response to cancer
The combination of checkpoint inhibitor antibodies and ADCs are used to induce or enhance the immune response against disease-associated antigens, such as tumor-associated antigens.
The checkpoint inhibitor antibodies against PD1 are one of the most promising avenues of immunotherapy of immunotherapy for cancer and comprise lambrolizumab, nivolumab, pidilizumab, etc. that encompass the anti-PD-1 antibodies lambrolizumab, nivolumab and pidilizumab of the instant claims.
The anti-CD25 daclizumab-IR700 or basiliximab-IR700 agents target the cell surface protein
CD25 analogously to the targeting of the anti-CD25 antibody-IR700 of the instant claims.
The anti-PD-1 checkpoint inhibitor antibodies lambrolizumab, nivolumab, pidilizumab bind PD-1 analogously to that of the binding of the anti-PD-1 checkpoint inhibitor antibodies of the instant
claims.
The administration of the combination of daclizumab-IR700 or basiliximab-IR700 and the anti-
PD-1 checkpoint inhibitor antibody lambrolizumab, nivolumab, pidilizumab encompass the method of steps of administering an immune checkpoint inhibitor and an anti-CD25 antibody-IR700 conjugate for
PIT of the instant claims.
Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of claimed invention that the administration of the daclizumab-IR700 or basiliximab-IR700 conjugates predictably results in killing immunosuppressive cells upon the administration of dose of NIR light of at least 30 J cm-2, at least 50 J cm-2, at least 100 J cm-2 or at least 500 J cm-2, etc. at a wavelength of 660-740 nm that encompasses the dose of from at or about 25 J cm-2 to at or about 400 J cm-2 at a wavelength of 600 nm to 850 nm of the instant claims. The addition of the anti-PD-1 checkpoint inhibitor antibody in combination provides the extra added advantage of enhancing the anti-tumor effects of the PIT of Kobayashi by inducing and/or enhancing the immune response against tumor-associated antigens.
Applicant asserts that Chang et al. is focused on methods of treatment of cancer comprising administering a combination therapeutic that includes any combination of two or more of: (i) leukocyte redirecting bispecific antibodies, (ii) antibody-drug conjugates, (iii) interferons such as such as interferon-a, interferon-3 or interferon-X (most preferably interferon- a), and/or (iv) checkpoint inhibitor antibodies. Chang et al. includes a long list of examples of each of these types of agents. Chang et al. does not identify or suggest any specific combination of an anti-CD25 antibody as the targeting agent of a bispecific antibody or ADC, let alone a phototoxic conjugate, and an immune checkpoint inhibitor as the co-administered therapy. Moreover, when read as a whole, it is clear that among the listed agents are agents that function to kill tumor cells directly. For example, paragraph such as [0009], [0010], [0022] and [0135] describe that bispecific antibodies redirect T cells or NK cell to kill tumor cells. There is no mention in Chang et al. of immunosuppressive cells, let alone targeted killing of immunosuppressive
cells.
The Examiner asserts that the reference of Chang et al. was not used to teach of any specific
combination of a phototoxic conjugate and immune checkpoint inhibitor for targeted killing of
immunosuppressive cells.
The reference of Chang et al. was explicitly used to teach of treating cancer via immunotherapy by the administration of a combination of two or more agents, such as antibody-drug conjugates (ADCs) and/or checkpoint inhibition antibodies for inducing an immune response to cancer as well as that stated above.
The combination of an antibody-drug conjugate with an anti-PD-1 checkpoint inhibitor antibody provides the advantage of enhancing the anti-tumor effects of the photoimmunotherapy by inducing
and/or enhancing the immune response against tumor-associated antigens.
Applicant asserts that Jain et al. is directed to a method of improving the delivery or efficacy of a therapy in a subject, such as a cancer therapy, that involves administration of an anti-hypertensive and/or a collagen-modifying agent (AHCM; e.g., angiotensin II antagonist, such as losartan) in addition to the therapy (e.g., cancer therapy). Photodynamic therapy (PDT) and ipilimumab (an example of immunotherapy) are individually mentioned as only as examples of a cancer therapy, within a list of other cancer therapies including radiation and surgery, to be used in combination with the AHCM to improve the delivery or efficacy of the therapy. There is no teaching or suggestion of a combination therapy combining a PDT agent and ipilimumab in the absence of the AHCM. As taught in Jain et al., the AHCM enhances the delivery or efficacy of the PDT or the immunotherapy (e.g., an immune checkpoint inhibitor). Thus, Jain et al. is focused on completely different combination therapy methods for a completely different purpose: specifically the requirement for AHCM along with a second agent or therapy (either AHCM and a PDT agent, or AHCM and an immunotherapy agent).
Further, the photodynamic therapy (PDT) taught in Jain et al. is completely different in the biological mechanism and immunological response associated with photoimmunotherapy (PIT) recited in the present claims. At a minimum, the PDT agents photosensitizing agents administered for the PDT are described by Jain et al. are naked photosensitizing agents and do not possess a targeting moiety. In stark contrast, in photoimmunotherapy (PIT) as claimed, the IR700 is conjugated to an antibody or antibody fragment that results in targeting the conjugate to specific target cells so that the phototoxicity effected upon illumination is directed to only targeted cells. Thus, any teachings of Jain et al. related to PDT are not relevant or applicable to photoimmunotherapy methods, including those described in the instant application or in combination with Kobayashi et al.
The Examiner asserts that the reference of Jain was not used to teach PIT but was used to teach of the administration of a combination of cancer therapy agents including a checkpoint inhibitor prior to (e.g. at least one, two, three, etc. days or one, two or three, etc. weeks) sequentially and/or concurrently with cancer therapy (e.g. photosensitizer PDT) for the treatment of squamous cell cancer (e.g. squamous neck cancer, etc.).
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to administer the checkpoint inhibitor before, sequentially and/or concurrently with cancer therapy as certain cancers may show elevated levels of extracellular matrix components in response to administered radiation.
Applicant asserts that Yoon is a review article that describes photosensitizers and light delivery for PDT. Among the reviewed photosensitizers are phthalocyanines, and Yoon also describes basic principles of PDT, including that the penetration of light through tissue can depend on the tissue type and wavelength. Yoon describes various wavelengths and light delivery systems. Mizeret also teaches a light diffuser for PDT, and the properties (e.g., diameter) of the device. The mention of the light diffusers are in the context of PDT, whereas the presently claimed combination therapy is for use in photoimmunotherapy (PIT). As discussed above the PDT in the cited references and PIT as claimed herein are different therapy methods, with different biological mechanisms and results. Nowhere does Yoon and Mizeret teach using an immune checkpoint inhibitor in combination with PIT, nor any of the light diffusers for use for PIT.
The Examiner asserts that the reference of Yoon was not used to teach of PIT or the combination of immune checkpoint inhibitor and PIT but was used to teach of the use of light delivery systems include cylindrical diffusing tips of various lengths and flexibility or fiber optics with a lens. The light delivery devices should be clinically oriented to give enough dosimetry with standardization showing maximum efficiency with minimum normal tissue injury.
The light delivery lasers have advantages, such as easy coupling with fiber optics following direct delivery of homogeneous and ample amount of light to the target site. The design and development of fiber optic delivery devices should be made with a few considerations, such as sufficient power delivery, compatibility with clinical instrumentation (i.e., endoscopes), and proper type of the fiber optic delivery tip to correspond to tumor shape, volume size or cavity area.
The reference of Mizeret was not used to teach of the combination of immune checkpoint inhibitor and PIT but was used to teach that cylindrical light diffusers that have a very high length to diameter that can be 100 mm or more and outer diameter of 1 mm or less, such as 0.75 mm external diameter of the optical fiber.
The reference of Kobayashi teaches of the use of fiber-couped laser diodes with diffuser tips to deliver the NIR light within several centimeters of otherwise inaccessible tumors located deep into the body surface as well as that stated above.
It would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to utilize cylindrical diffuser tips, for the method of Kobayashi, with lengths between 0.5 and 5 cm for PIT of tumors as Yoon teaches that cylindrical diffusers are commonly used in
lengths of 1 to 9 cm range depending on the specific application.
It would have been obvious to one of ordinary skill in the art before the effective filing date of
the claimed invention that cylindrical diffuser tips are microlens-tipped as Mizeret teaches that cylindrical light diffusers for PDT can be 10 cm long and have a micro-tip diameter of 0.75 mm for
surface illumination.
Response to Arguments
Applicant's arguments filed 10/2/25 have been fully considered but they are not persuasive.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double
patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
Claims 209-214,218,219 and 222-234 are rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-7,10-24 and 27 of U.S. Patent No. 11,154,620B2 as stated in the office action mailed 4/3/25.
Applicant respectfully requests that the Office hold the subject provisional double patenting rejection in abeyance until such time as the claims at issue are deemed otherwise allowable.
The claims are not allowable at this time and therefore, the rejection is maintained.
Claims 209-214,218-225,227 and 232-234 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1,4,10,11,13,16,18,20-24,30,33,41,49,51,52 and 54 of copending Application No. 17/630,854 as stated in the office action
mailed 4/3/25.
Applicant notes that if a provisional nonstatutory double patenting rejection is the only rejection remaining in an application having the earlier patent term filing, the examiner should withdraw the rejection in the application having the earlier patent term filing and permit that application to issue as a patent. The Applicant respectfully requests withdrawal of the provisional nonstatutory double patenting rejection because the US Application No. 17/630,854 is a later-filed application and the present application was filed first.
The provisional nonstatutory double patenting rejection of copending Application No. 17/630,854 is not the only remaining rejection in the application and therefore, the rejection is maintained.
Conclusion
No claims are allowed at this time.
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 MELISSA JEAN PERREIRA whose telephone number is (571)272-1354. The examiner can normally be reached M9-3, T9-3, W9-3, Th9-2, F9-2.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Michael Hartley can be reached at 571-272-0616. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/MELISSA J PERREIRA/Examiner, Art Unit 1618
/Michael G. Hartley/Supervisory Patent Examiner, Art Unit 1618