DETAILED ACTION
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 .
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on 09/24/2025 has been entered.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. The effective filing date for the instant claims is 09/30/2019 based on the filing date of PRO 62/907,773.
Status of Claims
The amended claims filed 09/24/2025 are acknowledged and entered. Claims 2-14, 16-19, 27-28, and 31-51 are cancelled. Claim 1 is amended. Claims 1, 15, 20-26 and 29-30 are pending. Claims 1, 15, 20-26 and 29-30 are examined on their merits.
Response to Remarks filed 09-24-2025
Applicant’s arguments and amendments with respect to the 35 USC 103 rejections of claims 1, 15, 20-26 and 29-30 have been fully considered and are not persuasive.
Applicant asserts that neither Woessner or Lokich provide motivation for combining the teachings. Regarding motivation, one of ordinary skill in the art would be motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of Woessner et al and Lokich et al to arrive at a method of treating a PDL1 positive DLBCL with MEDI4736, an antisense compound targeted to STAT3, and Cisplatin. One of ordinary skill in the art would have been motivated to do so, because Woessner et al teach the treatment of a subject having PDL1 positive DLBCL with MEDI4736 and an antisense compound targeted to STAT3. Furthermore, based on the teachings of Lukich et al, one of ordinary skill in the art would have been motivated to treat refractory DLBCL with cisplatin as cisplatin works better than carboplatin in some cancers. As such one of ordinary skill in the art would have been motivated to modify the teachings of Woessner et al, which teaches the treatment of a subject having PDL1 positive DLBCL with MEDI4736 and an antisense compound targeted to STAT3, to further include treatment with cisplatin because there would have been a reasonable expectation that the resultant invention, which comprises the administration of three anti-cancer medicaments, is effective in treating DLBCL.
Regarding unexpected results, Applicant states ‘there is nothing in the combination of Woessner and Lokich that provides one of skill with a reasonable expectation that therapeutic treatment cycle including a combination of MEDI4736, a STAT3 ASO, and cisplatin would be effective to induce a complete response in subjects who have DLBCL.’ However, as discussed above, it would be obvious to combine MEDI4736, a STAT3 ASO, and cisplatin based on the teachings of Woessner et al and Lokich et al. Furthermore, Lokich et al discloses that cisplatin resulted in complete responses in cancer treatments (Lokich et al, Table 3, pg. 17).
Therefore, the 35 USC 103 rejections of claims 1, 15, 20-26 and 29-30 are maintained for reasons of record in light of Woessner et al and Lukich et al.
Response to Remarks filed 05-30-2025
Applicant’s arguments and amendments with respect to the 35 USC 103 rejections of claims 1, 15, 20-26 and 29-30 have been fully considered and are not persuasive.
Specifically, the amendments do not overcome the prior art of Woessner et al and Lokich et al. and the examiner does not agree that there is no motivation to combine the teachings of Woessner et al and Lokich et al or that the results of the instant application are unexpected.
With respect to the teachings of Woessner et al., Applicant asserts that “[e]ven though Woessner may describe a method for treating Diffuse Large B-Cell Lymphoma (DLBCL) with 1 mg/kg to 20 mg/kg MEDI4736 and an antisense compound targeted to STATS, its lacks any guidance that would motivate one of skill in the art to modify its method to include a chemotherapeutic agent such as carboplatin… Further, any guidance that Woessner provides relating to a therapy comprising a third agent only describes one specific agent, tremelimumab (see, Woessner at page 39, lines 18- 21). Accordingly, Woessner provides no suggestion or guidance that reasonably motivates one of skill to a treatment regimen that would include MEDI4736 and AZD9150 in combination with any active agent other than tremelimumab.”
With respect to the teachings of Lokich et al., Applicant asserts that while Lokich may compare the dose and response rate of carboplatin and cisplatin in several studies (Lokich et al., Tables 2 and 3), those comparisons only relate to solid tumor cancers such as ovarian cancer (Table 2) or lung, head and neck, and bladder cancers (Table 3). Further, the data tables do not demonstrate clearly that cisplatin is more effective than carboplatin. For example, the ovarian cancer studies show that carboplatin is more effective than cisplatin as a first line therapy in ovarian cancer in two of the three single agent studies and in two of the five combination studies (Lokich et al., Table 2). Thus, not only does Lokich fail to provide any guidance that compares cisplatin and carboplatin in non-solid tumors (e.g., blood cancers such as DLBCL), its disclosure merely infers that cisplatin might be more effective than carboplatin in treating some solid tumor cancers. This amount of guidance is not adequate to either cure the deficiencies of Woessner, or to motivate one of skill in the art to modify Woessner in a way that arrives at the combination of features recited in Applicant's pending claims.
Applicant further asserts that the instant application demonstrates that the combination therapy recited in the pending claims is unexpectedly more effective in inhibiting continued tumor growth when compared either to chemotherapy alone or to a combination therapy comprising an antisense compound and anti-PDI agent (see, FIGs. 2F-2M). Further, the experimental data demonstrates that at least two patients had complete response with the claimed combination therapy, where the monotherapy and the double combination therapies failed to achieve any complete responders (see FIG. 2K-2M). No such results could have been reasonably derived or expected based on the guidance provided by the combination of the Woessner and Lokich references.
Applicant’s arguments with respect to Woessner et al. and Lokich et al have been fully considered but are not deemed persuasive. It is initially noted that “[o]ne cannot show nonobviousness by attacking references individually where the rejections are based on combinations of references. In re Keller, 642 F.2d 413, 208 USPQ 871 (CCPA 1981); In re Merck & Co., Inc., 800 F.2d 1091, 231 USPQ 375 (Fed. Cir. 1986).”
Regarding the amendment to claim 1, Woessner et al teach a method for treating Diffuse Large B-Cell Lymphoma (DLBCL) (Claim 14 of Woessner et al).
Regarding the amendment to claim 21, Woessner et al teach that the DLBCL may be at least 20% PDL1 positive (Woessner et al, pg. 31, lines 3-12).
Therefore, the amendments do not overcome the prior art of the previous rejections.
Regarding motivation, one of ordinary skill in the art would be motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of Woessner et al and Lokich et al to arrive at a method of treating a PDL1 positive DLBCL with MEDI4736, an antisense compound targeted to STAT3, and Cisplatin. One of ordinary skill in the art would have been motivated to do so, because Woessner et al teach the treatment of a subject having PDL1 positive DLBCL with MEDI4736 and an antisense compound targeted to STAT3. Furthermore, based on the teachings of Lukich et al, one of ordinary skill in the art would have been motivated to treat refractory DLBCL with cisplatin as cisplatin works better than carboplatin in some cancers. As such one of ordinary skill in the art would have been motivated to modify the teachings of Woessner et al, which teaches the treatment of a subject having PDL1 positive DLBCL with MEDI4736 and an antisense compound targeted to STAT3, to further include treatment with cisplatin because there would have been a reasonable expectation that the resultant invention, which comprises the administration of three anti-cancer medicaments, is effective in treating DLBCL.
Regarding unexpected results, the results of instant Figures 2F-2M show the added affects that would be reasonably expected when combining two vs. three treatments. One of ordinary skill in the art would reasonably expect that more treatment would result in more effect. The results presented in the instant application simply show that there is more of an effect when three treatments are combined as compared to two which is obvious in the art.
Therefore, the 35 USC 103 rejections of claims 1, 15, 20-26 and 29-30 are maintained for reasons of record in light of Woessner et al and Lukich et al.
Claim Rejections - 35 USC § 103- New Rejection
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) 1, 15, 20-26, 29, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Woessner et al (WO 2016/062722, A1, published 28 April 2016) in view of Lisenko et al (Lisenko et al, BMC Cancer, 2016, 16;267, 1-7)
Regarding Claim 1, Woessner et al teaches a method for treating Diffuse Large B-Cell Lymphoma (DLBCL) with 1mg/kg to about 20mg/kg MEDI4736 (Claim 14 of Woessner et al) and an antisense compound targeted to STAT3 (Claim 14 of Woessner et al. and AZD9150 defined as an antisense oligonucleotide and an example of an antisense compound targeted to STAT3, on page 3, line 31). Additionally, Woessner et al teaches the patient has previously received treatment with at least one chemotherapeutic agent, including carboplatin. (Woessner et al, page 44, line 30). Woessner et al doesn’t teach using 55mg/m2 to about 65 mg/m2 cisplatin.
Lisenko et al teach the use of cisplatin at 25mg/m2 and 100mg/m2 doses in DLBCL (Lisenko et al, pg.1, Background section and pg. 2, Modified R-DHAP Regimen section).
One of ordinary skill in the art would be motivated with a reasonable expectation of success at the effective filing date of the invention to combine the teachings of Woessner et al and Lisenko et al to arrive at a method of treating a PDL1 positive DLBCL with MEDI4736, an antisense compound targeted to STAT3, and Cisplatin. One of ordinary skill in the art would have been motivated to do so, because Woessner et al teach the treatment of a subject having PDL1 positive DLBCL with MEDI4736 and an antisense compound targeted to STAT3. Additionally, Lisenko et al teach the use of cisplatin in refractory DLBCL. As such one of ordinary skill in the art would have been motivated to modify the teachings of Woessner et al, which teaches the treatment of a subject having PDL1 positive DLBCL with MEDI4736 and an antisense compound targeted to STAT3, to further include treatment with cisplatin because there would have been a reasonable expectation that the resultant invention, which comprises the administration of three anti-cancer medicaments, is effective in treating DLBCL.
It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Regarding Claim 15, the method of claim 1 is discussed above. Lisenko et al teach the use of cisplatin at 25mg/m2 and 100mg/m2 doses in DLBCL (Lisenko et al, pg.1, Background section and pg. 2, Modified R-DHAP Regimen section). It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art. Thus, Applicant should not merely rely upon counsel’s arguments in place of evidence in the record.
Regarding Claims 20 and 21, the method of claim 1 is discussed above. Woessner et al discloses DLBCL (page 63, claim 10 of Woessner et al) and the method wherein the cancer cells express PD-L1 (i.e., claim 20; page 63, claim 11 of Woessner et al). Thus, the cancer is a PD-L1 positive DLBCL (i.e., claim 21)
Regarding Claims 22-25, the method of claim 1 is discussed above. Woessner et al discloses the agents are administered simultaneously, separately or sequentially (page 27, line 20).
With respect to the order of steps, it is noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959)). See MPEP §2144.04 IV C. The claimed order of steps is an obvious variant of the steps of the cited prior art.
Regarding Claim 26, the method of claim 25 is discussed above. Woessner et al discloses at least three doses can be administered of each agent (page 40, paragraph 2). It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art. Thus, Applicant should not merely rely upon counsel’s arguments in place of evidence in the record.
Regarding Claim 29, the method of claim 1 is discussed above. Woessner et al discloses changes in the CD11b+/GR1 (Ly6C/Ly6G)+ population (Figure 5).
Regarding Claim 30, the method of claim 1 is discussed above. Woessner et al discloses the method wherein the method results in an increase in progression free survival and/ or overall survival as compared to the administration of either the MEDI4736 or AZD9150 alone (page 64 claim 20 of Woessner et al).
Claim Rejections - 35 USC § 103 (Previous Rejections are all Maintained)
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) 1, 15, 20-26, 29, and 30 are rejected under 35 U.S.C. 103 as being unpatentable over Woessner et al (WO 2016/062722, A1, published 28 April 2016) in view of Lokich et al (Carboplatin versus cisplatin in solid tumors: an analysis of the literature." Annals of oncology 9.1 (1998): 13-21. (Year: 1998))
Regarding Claim 1, Woessner et al teaches a method for treating Diffuse Large B-Cell Lymphoma (DLBCL) with 1mg/kg to about 20mg/kg MEDI4736 (Claim 14 of Woessner et al) and an antisense compound targeted to STAT3 (Claim 14 of Woessner et al. and AZD9150 defined as an antisense oligonucleotide and an example of an antisense compound targeted to STAT3, on page 3, line 31). Additionally, Woessner et al teaches the patient has previously received treatment with at least one chemotherapeutic agent, including carboplatin. (Woessner et al, page 44, line 30). Woessner et al doesn’t teach using 55mg/m2 to about 65 mg/m2 cisplatin.
Lokich et al discloses that in some cancers cisplatin elicits an improved response rate in patients when compared to carboplatin (Lokich et al, Table 3, page 17) making it obvious for one skilled in the art to try using cisplatin instead of carboplatin. Furthermore, Lokich et al discloses a dose of cisplatin at 50mg/m2 (Lokich et al, page 18, column 2, line 6).
It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists (see In re Wertheim, 541 F.2d 257, 191 USPQ 90 (CCPA 1976); In re Woodruff, 919 F.2d 1575, 16 USPQ2d 1934 (Fed. Cir. 1990); Titanium Metals Corp. of America v. Banner, 778 F2d 775. 227 USPQ 773 (Fed. Cir. 1985) (see MPEP 2144.05.01).
The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” In re Aller, 220 F.2d 454, 456, 105 USPQ 233, 235 (CCPA 1955). See MPEP 2144.05 II.
Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art.
Regarding Claim 15, the method of claim 1 is discussed above. Lokich et al discloses low dose of cisplatin at 50mg/m2 (Lokich et al, page 18, column 2, line 6). It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art. Thus, Applicant should not merely rely upon counsel’s arguments in place of evidence in the record.
Regarding Claims 20 and 21, the method of claim 1 is discussed above. Woessner et al discloses DLBCL (page 63, claim 10 of Woessner et al) and the method wherein the cancer cells express PD-L1 (i.e., claim 20; page 63, claim 11 of Woessner et al). Thus, the cancer is a PD-L1 positive DLBCL (i.e., claim 21)
Regarding Claims 22-25, the method of claim 1 is discussed above. Woessner et al discloses the agents are administered simultaneously, separately or sequentially (page 27, line 20).
With respect to the order of steps, it is noted that the courts have held that any order of performing process steps is prima facie obvious in the absence of new or unexpected results (In re Gibson, 39 F.2d 975, 5 USPQ 230 (CCPA 1930); Ex parte Rubin, 128 USPQ 440 (Bd. App. 1959)). See MPEP §2144.04 IV C. The claimed order of steps is an obvious variant of the steps of the cited prior art.
Regarding Claim 26, the method of claim 25 is discussed above. Woessner et al discloses at least three doses can be administered of each agent (page 40, paragraph 2). It is noted that the courts have stated where the claimed ranges “overlap or lie inside the ranges disclosed by the prior art” and even when the claimed ranges and prior art ranges do not overlap but are close enough that one skilled in the art would have expected them to have similar properties, a prima facie case of obviousness exists. The courts have also found that “where the general conditions of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation.” Therefore, the claimed ranges merely represent an obvious variant and/or routine optimization of the values of the cited prior art. Thus, Applicant should not merely rely upon counsel’s arguments in place of evidence in the record.
Regarding Claim 29, the method of claim 1 is discussed above. Woessner et al discloses changes in the CD11b+/GR1 (Ly6C/Ly6G)+ population (Figure 5).
Regarding Claim 30, the method of claim 1 is discussed above. Woessner et al discloses the method wherein the method results in an increase in progression free survival and/ or overall survival as compared to the administration of either the MEDI4736 or AZD9150 alone (page 64 claim 20 of Woessner et al).
It is noted that the subject matter of a properly construed claim is defined by the terms that limit its scope. It is this subject matter that must be examined. As a general matter, the grammar and intended meaning of terms used in a claim will dictate whether the language limits the claim scope. Language that suggests or makes optional but does not require steps to be performed or does not limit a claim to a particular structure does not limit the scope of a claim or claim limitation. “Wherein” clauses are examples of language that may raise a question as to the limiting effect of the language in a claim. See MPEP 2103 I.C. and MPEP § 2111.04.
It is also noted that a “wherein” clause, such as that in claims 29 and 30, must give “meaning and purpose to the manipulative steps.” See, MPEP § 2111.04.
Conclusion
No claims are 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 extension fee 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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/J.K.D./Examiner, Art Unit 1642
/NELSON B MOSELEY II/Primary Examiner, Art Unit 1642