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
The Amendments and Remarks filed 11/14/25 in response to the Office Action of 5/14/25 are acknowledged and have been entered.
Claims 1, 2, 7-9, 11-13, 16-19, 23-27, and 32 are pending.
Claims 1, 11, 18, 19, and 32 have been amended by Applicant.
Claims 1, 2, 7-9, 11-13, 16-19, 23-27, and 32 are currently under examination.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Objection Withdrawn
The objection to claim 1 is withdrawn.
Rejections Withdrawn
The rejections under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, are withdrawn.
The rejection under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, is withdrawn.
Rejections Maintained
Claim Rejections - 35 USC § 103
Claims 1, 2, 9, 11-13, and 16-19 remain rejected under 35 U.S.C. 103(a) as being unpatentable over Thompson et al (Drug Discovery Today, 2010, 15(11/12): 468-473; “Thompson 1”) in view of Thompson et al (mAbs, 2009, (1-4): 348-356; “Thompson2”) and Oka (WO2021060496A1) (9/25/20; claim priority to 9/26/19; English translation at Google Patents: https://patents.google.com/patent/WO2021060496A1/en?oq=WO+2021060496+A1).
Thompson1 teaches molecules comprising reversibly inhibited therapeutic antibodies for treating cancer that are bound to photolabile moieties which when subjected to light are released from the antibodies which thereby regain their ability to provide therapeutic benefit to treat cancer (pages 469-470 and Figure 1, in particular). Thompson1 teaches such therapeutic antibodies include anti-CD3 antibodies, wherein such molecules bind CD3 and activate T-cells after UV light treatment (left column on page 470 and Figure 2, in particular). In vivo, such reversibly inhibited anti-CD3 antibodies reduced tumor growth when injected into subjects with cancer and irradiated with UV light (right column on page 470, in particular). Thompson1 teaches the benefit of using such molecules comprising reversibly inhibited therapeutic antibodies is they can reduce side-effects by using light to make activity of the antibodies region-specific (Abstract, in particular). Thompson1 further teaches 1-(2-nitrophenyl)ethanol (NPE) residues as such photolabile moieties (left column on page 470 and Figure 1, in particular).
Thompson1 does not specifically teach photolabile moieties of the reversibly inhibited therapeutic antibodies are linked to the antibodies via the hydrophilic polymer polyethylene glycol. However, these deficiencies are made up in the teachings of Thompson2 and Oka.
Thompson2 teaches NPE photolabile moieties of Thompon1 cleave upon irradiation with UV light, resulting in reversal inhibition the antibodies (left column on page 349, in particular). Thompson2 teaches, after irradiation, the moieties regain 25-30% of their original uncloaked binding capacities (right column on page 349, in particular). Further, Thompson2 specifically provides motivation to improve light cutting efficiency. At the left column on page 351, Thompson2 teaches not NPE photolabile moieties had been reactivated by 5 minutes of in vivo by UV radiation. Thompson2 addressed this by increasing the amount of injected antibody and the irradiation time.
Oka teaches a method of improving the light cutting efficacy of a photocleaving/light-cutting linker (“light-cutting linker” is defined by Oka as a compound containing a light-cutting unit that is decomposed by light irradiation) by inserting a spacer, such as the hydrophilic polymer polyethylene glycol, between the light-cutting linker and the particle to which it is bound (see Abstract and claims 1 and 4 of Oka, in particular). See Description Text and claim 5 of Oka as further teaching the linker can also be linked to a “probe molecule”, such as an antibody.
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to treat a subject with cancer comprising performing a combined method comprising administering reversibly inhibited therapeutic antibodies of Thompson1 and Thompson2 to the subject wherein the NPE photolabile moieties are attached to the therapeutic antibodies via the hydrophilic polymer polyethylene glycol because reversal of inhibition of the therapeutic antibodies of Thompson1 and Thompson2 occurs when the NPE photolabile moieties are cleaved upon irradiation with UV light and Oka teaches light cutting efficacy of a photocleaving/light-cutting linker (“light-cutting linker” is defined by Oka as a compound containing a light-cutting unit that is decomposed by light irradiation) is improved by inserting the hydrophilic polymer polyethylene glycol between the light-cutting linker and the particle to which it is bound. This is an example of some teaching, suggestion, or motivation in the prior art that would have led one of ordinary skill to modify the prior art reference or to combine prior art reference teachings to arrive at the claimed invention. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Response to Arguments
In the Reply of 11/14/25, Applicant argues Oka is silent regarding use of a photolabile moiety as part of a binding molecule to enhance immune system effectiveness. Applicant further argues a lack of motivation to improve light cutting efficiency of Thompson 1 or Thompson 2 because effective release was observed within 5-10 minutes of illumination with a low-power soft UV lamp within the UV-A range. Applicant further argues increasing “cutting efficacy” for no clear reason would be expected by one skilled in the art to complicate it intended clinical use at it would result in higher antibody activation beyond the specific area being targeted. Applicant further states use of photolabile groups with a hydrophilic polymer is particularly advantageous in the context of increasing half-life of a binding molecule following administration.
The amendments to the claims and the arguments found in the Reply of 11/14/25 have been carefully considered, but are not deemed persuasive. In regards to the argument Oka is silent regarding use of a photolabile moiety as part of a binding molecule to enhance immune system effectiveness, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). However, it is noted Thompson1 teaches use of a photolabile moiety as part of a binding molecule to enhance immune system effectiveness by binding CD3 and activating T-cells after UV light treatment (left column on page 470 and Figure 2, in particular).
In regards to the argument of a lack of motivation to improve light cutting efficiency of Thompson 1 or Thompson 2 because effective release was observed within 5-10 minutes of illumination with a low-power soft UV lamp within the UV-A range, Thompson2 specifically provides motivation to improve light cutting efficiency. At the left column on page 351, Thompson2 teaches not enough NPE photolabile moieties had been reactivated by 5 minutes of in vivo by UV radiation. Thompson2 addressed this by increasing the amount of injected antibody and the irradiation time. As opposed to increasing the amount of injected antibody and irradiation time, the combined method improves light cutting efficiency by inserting a spacer, such as the hydrophilic polymer polyethylene glycol, between the light-cutting linker and the antibody. Therefore, the combined method has the benefit of requiring less administered antibody due to improved light cutting efficiency.
In regards to the statement that use of photolabile groups with a hydrophilic polymer is particularly advantageous in the context of increasing half-life of a binding molecule following administration, such a benefit would naturally flow from the combined method. Further, antibodies attached to hydrophilic polymer PEG are well-known in the prior art to exhibit reduced immunogenicity and increased half-lives (see Abstract of Chapman (Advanced Drug Delivery Reviews, 2002, 54: 531-545)).
Claim Rejections - 35 USC § 103
Claim(s) 1, 2, 7-9, 11-13, 16-19, 23-27, and 32 remain rejected under 35 U.S.C. 103 as being unpatentable over Thompson et al (Drug Discovery Today, 2010, 15(11/12): 468-473; “Thompson 1”) in view of Thompson et al (mAbs, 2009, (1-4): 348-356; “Thompson2”) and Oka (WO2021060496A1) (9/25/20), as applied to claims 1, 2, 9, 11-13, and 16-19 above, and further in view of Ngo et al (Cell Reports, 2016, 16: 1701-1716).
Teachings of Thompson1, Thompson2, and Oka are discussed above.
Thompson1, Thompson2, and Oka do not specifically teach methods of treating melanoma. However, these deficiencies are made up in the teachings of Ngo et al.
Ngo et al teaches methods of treating subjects with malignant melanoma comprising administering anti-CD47 antibodies to the subjects, which inhibit a “don’t-eat-me signal” on cancer cells, in combination with anti-CD271 antibodies (Figure 3 and left column on page 1702, in particular).
One of ordinary skill in the art would have been motivated, with a reasonable expectation of success, to perform the combined method of Thompson1, Thompson2, and Oka wherein the subject has malignant melanoma and the administered therapeutic antibodies of the reversibly inhibited therapeutic antibodies are an effective dose of anti-CD47 and anti-CD271 antibodies of Ngo that are irradiated with UV light at any tumor site of the subject because the combined method efficiently targets therapeutic antibodies with UV light at tumor sites and Ngo teaches anti-CD47 and anti-CD271 antibodies therapeutically target melanoma tumors. Therefore, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art, absent unexpected results.
Response to Arguments
In the Reply of 11/14/25, Applicant repeats arguments addressed above. Applicant further argues Ngo does not describe use of a photolabile moiety.
The amendments to the claims and the arguments found in the Reply of 11/14/25 have been carefully considered, but are not deemed persuasive. In regards to the argument Ngo does not describe use of a photolabile moiety, one cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. See In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986). However, it is noted Thompson1 teaches use of a photolabile moiety as part of a binding molecule to enhance immune system effectiveness by binding CD3 and activating T-cells after UV light treatment (left column on page 470 and Figure 2, in particular).
Conclusion
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.
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/SEAN E AEDER/Primary Examiner, Art Unit 1642