DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. Claims 16-31 are pending.
Claims 23, 24 and 26 have been amended.
Claims 16-31 are examined on the merits.
3. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Withdrawn Grounds of Rejection
Claim Rejections - 35 USC § 112
4. The rejection of claims 23 and 24 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of the amendments to the said claims, see Amendments to the Claims/Claim List submitted July 7, 2026, pages 3 and 4.
5. The rejection of claim 26 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention is withdrawn in light of the amendment to the claim deleting “or a derivative thereof”, see Amendments to the Claims/Claim List submitted July 7, 2026, page 4.
Maintained Grounds of Rejection
Claim Rejections - 35 USC § 103
6. 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.
7. The rejection of claim(s) 16-27 and 29-31 under 35 U.S.C. 103 as being unpatentable over Loew et al., US 2020/0071417 A1 (published March 5, 2020), and further in view of Terme et al., European Patent Application, EP 3269739 A1 (published 17 January 2018/ Foreign Patent Document #2 submitted October 13, 2023) is maintained.
Initially, Applicant recites independent claims 16 and 18, see Remarks, submitted July 7, 2026, page 7. Following are arguments, wherein Applicant states, “Figure 4B of the specification as filed shows that the anti-PD-1 antibody strongly potentiates the anti-metastatic effect of the anti-OAcGD2 antibody (see 8B6 alone versus 8B6+RPMI-14) and of 13-cis retinoic acid (see 13-cis RA alone versus 13-cis RA+RPMI-14). This unexpected result demonstrates a synergy between the anti-PD-1 antibody and the 13-cis retinoic acid /anti-OAcGD2 combination that relies not only on an anti-PD-1/anti-OAcGD2 interaction, but also on an anti-PD-1/13-cis retinoic acid cooperation.
Regarding Loew, Loew teaches multispecific molecules that bind to immunosuppressive myeloid cells and uses thereof in combination with immune checkpoint inhibitors such as an anti- PD1 compound or with a chemotherapeutic agent selected from a long list that includes retinoic acid.
However, Loew is silent on combining an anti-PD1 compound and retinoic acid. Moreover, Loew is silent on OAcGD2 or any anti-OAcGD2 compound, much less suggests that combining an anti-OAcGD2 compound with retinoic acid and an anti-PD1 or anti-PD-L1 compound would provide a technical effect in treating cancer.
It follows that one of ordinary skill in the art would not have been motivated to combine an anti-PD1 or anti-PD-L1 compound to retinoic acid and an anti-OAcGD2 compound for treating cancer in view of Loew.
Turning to Terme, Terme discloses anti-OAcGD2 antibodies comprising the VH/VL sequences recited in claim 23.
However, Terme is silent on any anti-PD1 or anti-PD-L1 compound, much less suggests that said anti-OAcGD2 antibodies would have a technical anti-cancer effect in combination with retinoic acid plus an anti-PD1 or anti-PD-L1 compound. Accordingly, Terme likewise does not remedy the deficiencies of Loew.
To improve the anticancer effect of an anti-PD1 or anti-PD-L1 therapy, one of ordinary skill in the art would have known that not any immunotherapy may be used with reasonable expectation of success (i.e. improved anticancer effect of the combination versus anti-PD1 single therapy). Importantly, neither Loew nor Terme mentions a combination comprising an anti-OAcGD2 compound and an anti-PD1 or anti-PD-L1 compound, let alone do they suggest a synergistic effect of combining an anti-OAcGD2 compound with retinoic acid and an anti-PD1 or anti-PD-L1 compound in treating cancer.
It follows that one of ordinary skill in the art would not have been motivated by Loew and Terme with a reasonable expectation of success to combine an anti-OAcGD2 compound with retinoic acid and an anti-PD1 or anti-PD-L1 compound for treating cancer. In other words, an attempt to bring in the isolated teaching Terme into Loew would amount to improperly picking and choosing features from different references without regard to the teachings of the references as a whole. While the required evidence of motivation to combine need not come from the applied references themselves, the evidence must come from somewhere within the record. In this case, there is nothing in the record supporting the Office Action's proposed combination.”, see Remarks spanning pages 7-9.
Applicant’s arguments and figure have been carefully considered, but the arguments have not been found persuasive.
“[A]ny superior property must be unexpected to be considered as evidence of non-
obviousness.” Pfizer, Inc. v. Apotex, Inc.,480 F.3d 1348, 1371 (Fed. Cir. 2007). The
Specification does not note the terms, “unexpected” or “superior” and other than
statements by attorney.
Reviewing Figure 4B it is clear that the therapeutic agents implemented in the assay are RPMI-14, an anti-PD-1 antibody, 8B6, an anti-OacGD2 antibody and 13-cis retinoic acid. The cancer is liver metastasis. While the combined effect expressed when the data is based upon (8B6 alone versus 8B6+RPMI-14) and (13-cis RA alone versus 13-cis RA+RPMI-14) cited in Figure 4B seems to read on synergistic, as the claims are written broadly reading on any isomeric form of a retinoic acid, an anti-PD1 antibody and any cancer the data does not provide such.
The arguments are not persuasive because when compared to the closest prior art herein, it is found to be directed to latent properties, not unexpected results. It would not have been unexpected for the claimed invention to achieve the results achieved by Applicant. The combination of references do teach the claimed invention. The teachings of all these references embody all three tenets of the requirements for establishing a proper case of obviousness.
Applicants have not established that the results achieved could be extrapolated to the claimed methods and thereby be unexpectedly superior compared to the closest prior art herein, which teaches the claimed limitations. See In re Baxter Travenol Labs., 952 F.2d 388, 392 (Fed. Cir. 1991). One of ordinary skill in the art could have reasonably expected to successfully combine the references for such a purpose because each reference indicates that a combination of anticancer therapeutic agents can be successfully administered and each agent complementing the other for the method
endpoint of treating cancer with the teachings herein, see all references.
The modification of the primary reference in light of the secondary references is
proper because the applied references are so related that the appearance of features
shown in one would suggest the application of those features to the other. See In re
Rosen, 673 F.2d 388, 213 USPQ 347 (CCPA 1982); In re Carter, 673 F.2d 1378, 213 USPQ
625 (CCPA 1982), and In re Glavas, 230 F.2d 447, 109 USPQ 50 (CCPA 1956). Further, it is
noted that case law has held that a designer skilled in the art is charged with knowledge
of the related art; therefore, the combination of old elements, herein, would have been
well within the level of ordinary skill. See In re Antle, 444 F.2d 1168,170 USPQ 285 (CCPA
1971) and In re Nalbandian, 661 F.2d 1214, 211 USPQ 782 (CCPA 1981). The combination of
references would not change the principle of operation of the prior art invention being modified, hence the teachings of the references are sufficient to render the claims prima
facie obvious. For the reasons of record and cited herein, the rejection is maintained.
Loew teaches “[m]ethods…treating a cancer in a subject by using a multispecific molecule described herein, e.g., using a pharmaceutical composition described herein.”, see page 31, section 300. Loew’s methods of treating cancer comprise a multispecific molecule comprising an anti-CSF1R antibody molecule and a PD-L1 antibody molecule, see page 11, section 0098. The multispecific molecule may further comprise a cytokine molecule, interleukin-2 (IL-2), see page 12, section 0105. A second therapeutic treatment comprises a check point inhibitor, an anti-PD1 antibody (e.g., Nivolumab, Pembrolizumab or Pidilizumab) or an anti-PD-L1 antibody, wherein the multispecific antibody molecule may further comprise a PD-L1 binding moiety, see page 13, sections 0121 and 0127; page 25, section 0226. “[T]he multispecific molecule is administered in combination with a low or small molecular weight chemotherapeutic agent. Exemplary low or small molecular weight chemotherapeutic agents include, but not limited to, 13-cis-retinoic acid (isotretinoin, ACCUTANE®).”, see page 36, section 0352.
“The multispecific molecule described herein, alone or in combination with a second therapy or a second therapeutic agent, can be used to treat a hyperproliferative disorder, a cancer,”, see page 31, section 0299. The combinatorial therapeutic regimen is able to treat breast cancer, small cell lung cancer, glioblastoma, neuroblastoma, see page 13, section 0126; page 31, section 0304; page 32, section 0305.
“In one embodiment, the multispecific molecule is administered in combination with a therapy, e.g., a cancer therapy (e.g., one or more of anti-cancer agents, immunotherapy, photodynamic therapy (PDT), surgery and/or radiation). The terms “chemotherapeutic,” “chemotherapeutic agent,” and “anti-cancer agent” are used interchangeably herein. The administration of the multispecific molecule and the therapy, e.g., the cancer therapy, can be sequential (with or without overlap) or simultaneous. Administration of the multispecific molecule can be continuous or intermittent during the course of therapy (e.g., cancer therapy).”, see page 36, section 351.
The Loew “…multispecific molecule further comprises one or more additional binding moieties (e.g., a third binding moiety, a fourth binding moiety, (e.g., a trispecific or a tetraspecific molecule)”, see page 11, section 0099.
Loew does not teach the combinatorial pharmaceutical composition comprises the taught retinoic acid and checkpoint compound with an anti-O-acetylated disialoganglioside (OAcG2) compound, wherein the anti-OacGD2 antibody compound comprises complementary-determining regions (CDRs) set forth in claim 21 and the light chain variable region (VL) with the sequence that is 100% sequence identical with Applicant’s SEQ ID NO: 7 and SEQ ID NO: 8.
Loew does not teach the anti-OAcGD2 antibody compound is comprised within the taught multispecific antibody comprising at least two antigen binding sites directed to OAcGD2 and PD1 or PD-L1.
However, Terme teaches the anti-OAcGD2 antibody compound comprising the same CDR sequences as Applicant’s cited in claim 21, and VL and VH having at least 85% sequence identity to SEQ ID NO: 7 and SEQ ID NO: 8, respectively and a humanized antibody, see sequence alignment at close of rejection; and page 2, sections 0006 and 0007. Terme also teaches the sequences that share 100% sequence identity with Applicant’s heavy chain variable region (VH) sequences for SEQ ID NO: 9, SEQ ID NO: 10, SEQ ID NO: 13, SEQ ID NO: 14, as well as variants of SEQ ID NO: 11, SEQ ID NO: 12, SEQ ID NO: 15, SEQ ID NO: 16, SEQ ID NO: 17, SEQ ID NO: 18, SEQ ID NO: 19.
Terme teaches a bispecific antibody that has binding specificity for two targets, see section 0048 spanning pages 6 and 7.
Terme further teaches the OAcGD2 ganglioside is expressed by neuroblastoma, as well as breast cancer and small cell lung cancer, see page 8, sections 0065; and page 9, sections 0073 and 0077.
It would have been obvious to one of ordinary skill in the art at the
effective filing date of the claimed invention to substitute the anti-CSF1R antibody molecule of Loew with the anti-OAcGD2 antibody compound of Terme with known structure given it has successfully targeted the OAcGD2 antigen for treatment of cancers expressing the OAcGD2 ganglioside, see the abstract; page 3, sections 0009, 0012, 0013; and entire document. Moreover, it would have been obvious to manufacture multispecific antibody with binding specificity for OAcGD2, thereby substituting the CSF1R binding moiety for the OAcGD2 binding moiety to treat OacGD2 expressing cancers.
One of ordinary skill in the art would have been motivated to do so
with a reasonable expectation of success by teachings in Terme that the target of the antibodies with known CDRs are art recognized as a plausible alternative, as well as the antibody within a pharmaceutical composition is suitable for intravenous administration for cancer therapy, see page 7, sections 0049-0053; page 8, sections 0064, 0065, 0071; and page 9, section 0073. Furthermore, one of ordinary skill in the art would have motivated to manufacture the multispecific antibody as it is art known they are able to target to molecules for the enhancement of effective treatment of cancers expressing a multitude of targets and/or antigens, Terme abstract and entire document; and entirety of Loew.
RESULT 4 from 1fus2fus3fus.aling450.rag database.
BEW79471
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BEW79471 standard; protein; 119 AA.
XX
AC BEW79471;
XX
DT 08-MAR-2018 (first entry)
XX
DE Humanized anti-OAcGD2 antibody heavy chain variable region, SEQ 70.
XX
KW OAcGD2 protein; antibody therapy; cancer; cytostatic; diagnostic test;
KW glioma; heavy chain variable region; humanized antibody; neuroblastoma;
KW neuroprotective; ophthalmological; prophylactic to disease;
KW retinoblastoma; therapeutic; tumor marker.
XX
OS Mus musculus.
OS Synthetic.
XX
CC PN EP3269739-A1.
XX
CC PD 17-JAN-2018.
XX
CC PF 15-JUL-2016; 2016EP-00001564.
XX
PR 15-JUL-2016; 2016EP-00001564.
XX
CC PA (OGDT-) OGD2 PHARMA.
XX
CC PI Terme M, Le Doussal J, Dorvillius M, Assouline B;
XX
DR WPI; 2018-04937Q/08.
XX
CC PT New humanized antibody against O-acetylated GD2 ganglioside (OAcGD2),
CC PT useful for preventing and/or treating cancer expressing the OAcGD2
CC PT ganglioside, e.g. neuroblastoma, glioma, and retinoblastoma.
XX
CC PS Example; SEQ ID NO 70; 122pp; English.
XX
CC The present invention relates to a novel humanized antibody against O-
CC acetylated GD2 ganglioside (OAcGD2) useful for preventing and/or treating
CC cancer. The invention further relates to: (1) a method for diagnosing a
CC cancer expressing the OAcGD2 ganglioside in a subject; and (2) a kit for
CC diagnosing a cancer expressing the OAcGD2 ganglioside in a subject. The
CC cancer chosen from neuroblastoma, glioma, retinoblastoma. The present
CC sequence is a humanized anti-OAcGD2 antibody heavy chain variable region,
CC used in the invention for preventing and/or treating cancer.
XX
SQ Sequence 119 AA;
Query Match 83.8%; Score 131.5; Length 119;
Best Local Similarity 33.7%;
Matches 28; Conservative 0; Mismatches 0; Indels 55; Gaps 2;
Qy 1 EFTFTDYY-----------------IRNRANGYTT------------------------- 18
|||||||| ||||||||||
Db 26 EFTFTDYYMTWVRQPPRKALEWLGFIRNRANGYTTEYNPSVKGRFTISRDNSQSIAYLQM 85
Qy 19 -------------ARVSNWAFDY 28
||||||||||
Db 86 NTLRTEDSATYYCARVSNWAFDY 108
RESULT 1 from 4fus5fus6fus.aling450.rag database.
BEW79488
(NOTE: this sequence has 1 duplicate in the database searched.
See complete list at the end of this report)
ID BEW79488 standard; protein; 112 AA.
XX
AC BEW79488;
XX
DT 08-MAR-2018 (first entry)
XX
DE Humanized anti-OAcGD2 antibody light chain variable region, SEQ 87.
XX
KW OAcGD2 protein; antibody therapy; cancer; cytostatic; diagnostic test;
KW glioma; humanized antibody; light chain variable region; neuroblastoma;
KW neuroprotective; ophthalmological; prophylactic to disease;
KW retinoblastoma; therapeutic; tumor marker.
XX
OS Mus musculus.
OS Synthetic.
XX
CC PN EP3269739-A1.
XX
CC PD 17-JAN-2018.
XX
CC PF 15-JUL-2016; 2016EP-00001564.
XX
PR 15-JUL-2016; 2016EP-00001564.
XX
CC PA (OGDT-) OGD2 PHARMA.
XX
CC PI Terme M, Le Doussal J, Dorvillius M, Assouline B;
XX
DR WPI; 2018-04937Q/08.
XX
CC PT New humanized antibody against O-acetylated GD2 ganglioside (OAcGD2),
CC PT useful for preventing and/or treating cancer expressing the OAcGD2
CC PT ganglioside, e.g. neuroblastoma, glioma, and retinoblastoma.
XX
CC PS Example; SEQ ID NO 87; 122pp; English.
XX
CC The present invention relates to a novel humanized antibody against O-
CC acetylated GD2 ganglioside (OAcGD2) useful for preventing and/or treating
CC cancer. The invention further relates to: (1) a method for diagnosing a
CC cancer expressing the OAcGD2 ganglioside in a subject; and (2) a kit for
CC diagnosing a cancer expressing the OAcGD2 ganglioside in a subject. The
CC cancer chosen from neuroblastoma, glioma, retinoblastoma. The present
CC sequence is a humanized anti-OAcGD2 antibody light chain variable region,
CC used in the invention for preventing and/or treating cancer.
XX
SQ Sequence 112 AA;
Query Match 79.5%; Score 97.8; Length 112;
Best Local Similarity 31.6%;
Matches 24; Conservative 0; Mismatches 0; Indels 52; Gaps 2;
Qy 1 QSLLKNNGNTFL----------------KVS----------------------------- 15
|||||||||||| |||
Db 27 QSLLKNNGNTFLSWYLQKSGQSPKLLIYKVSNRLSGVPDRFSGSGSGTYFTLKISRVEAE 86
Qy 16 -------SQSTHIPYT 24
|||||||||
Db 87 DLGVYFCSQSTHIPYT 102
RESULT 1 from 7.rag database.
BEW79446
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
ID BEW79446 standard; protein; 112 AA.
XX
AC BEW79446;
XX
DT 08-MAR-2018 (first entry)
XX
DE Humanized anti-OAcGD2 antibody light chain variable region, SEQ 45.
XX
KW OAcGD2 protein; antibody therapy; cancer; cytostatic; diagnostic test;
KW glioma; humanized antibody; light chain variable region; neuroblastoma;
KW neuroprotective; ophthalmological; prophylactic to disease;
KW retinoblastoma; therapeutic; tumor marker.
XX
OS Mus musculus.
OS Synthetic.
XX
CC PN EP3269739-A1.
XX
CC PD 17-JAN-2018.
XX
CC PF 15-JUL-2016; 2016EP-00001564.
XX
PR 15-JUL-2016; 2016EP-00001564.
XX
CC PA (OGDT-) OGD2 PHARMA.
XX
CC PI Terme M, Le Doussal J, Dorvillius M, Assouline B;
XX
DR WPI; 2018-04937Q/08.
XX
CC PT New humanized antibody against O-acetylated GD2 ganglioside (OAcGD2),
CC PT useful for preventing and/or treating cancer expressing the OAcGD2
CC PT ganglioside, e.g. neuroblastoma, glioma, and retinoblastoma.
XX
CC PS Claim 3; SEQ ID NO 45; 122pp; English.
XX
CC The present invention relates to a novel humanized antibody against O-
CC acetylated GD2 ganglioside (OAcGD2) useful for preventing and/or treating
CC cancer. The invention further relates to: (1) a method for diagnosing a
CC cancer expressing the OAcGD2 ganglioside in a subject; and (2) a kit for
CC diagnosing a cancer expressing the OAcGD2 ganglioside in a subject. The
CC cancer chosen from neuroblastoma, glioma, retinoblastoma. The present
CC sequence is a humanized anti-OAcGD2 antibody light chain variable region,
CC used in the invention for preventing and/or treating cancer.
XX
SQ Sequence 112 AA;
Query Match 88.5%; Score 269; Length 112;
Best Local Similarity 50.9%;
Matches 56; Conservative 0; Mismatches 54; Indels 0; Gaps 0;
Qy 3 VMTQSPXXLXXXXGXXXXXXCRXSQSXXKXXXXXXLXWXXQXPGXXPXXLIYXXSXRXXG 62
|||||| | | || ||| | | | | || | ||| | | |
Db 3 VMTQSPATLSLSPGERATLSCRSSQSLVKNQANTYLHWYQQKPGQAPRLLIYKVSNRLTG 62
Qy 63 XPXRFSGSGSGTXFTLXIXXXXXEDXXXYXCXQXXXXXYTFGXGTKVEIK 112
| ||||||||| ||| | || | | | |||| |||||||
Db 63 IPARFSGSGSGTDFTLTISSLQAEDFAVYYCSQSTHIPYTFGGGTKVEIK 112
RESULT 1 from 8.rag database.
BEW79443
(NOTE: this sequence has 2 duplicates in the database searched.
See complete list at the end of this report)
ID BEW79443 standard; protein; 119 AA.
XX
AC BEW79443;
XX
DT 08-MAR-2018 (first entry)
XX
DE Humanized anti-OAcGD2 antibody heavy chain variable region, SEQ 42.
XX
KW OAcGD2 protein; antibody therapy; cancer; cytostatic; diagnostic test;
KW glioma; heavy chain variable region; humanized antibody; neuroblastoma;
KW neuroprotective; ophthalmological; prophylactic to disease;
KW retinoblastoma; therapeutic; tumor marker.
XX
OS Mus musculus.
XX
CC PN EP3269739-A1.
XX
CC PD 17-JAN-2018.
XX
CC PF 15-JUL-2016; 2016EP-00001564.
XX
PR 15-JUL-2016; 2016EP-00001564.
XX
CC PA (OGDT-) OGD2 PHARMA.
XX
CC PI Terme M, Le Doussal J, Dorvillius M, Assouline B;
XX
DR WPI; 2018-04937Q/08.
XX
CC PT New humanized antibody against O-acetylated GD2 ganglioside (OAcGD2),
CC PT useful for preventing and/or treating cancer expressing the OAcGD2
CC PT ganglioside, e.g. neuroblastoma, glioma, and retinoblastoma.
XX
CC PS Claim 4; SEQ ID NO 42; 122pp; English.
XX
CC The present invention relates to a novel humanized antibody against O-
CC acetylated GD2 ganglioside (OAcGD2) useful for preventing and/or treating
CC cancer. The invention further relates to: (1) a method for diagnosing a
CC cancer expressing the OAcGD2 ganglioside in a subject; and (2) a kit for
CC diagnosing a cancer expressing the OAcGD2 ganglioside in a subject. The
CC cancer chosen from neuroblastoma, glioma, retinoblastoma. The present
CC sequence is a humanized anti-OAcGD2 antibody heavy chain variable region,
CC used in the invention for preventing and/or treating cancer.
XX
SQ Sequence 119 AA;
Query Match 95.4%; Score 432; Length 119;
Best Local Similarity 69.5%;
Matches 82; Conservative 0; Mismatches 36; Indels 0; Gaps 0;
Qy 2 VQLXESGGGLVXPGXSLRLSCXXSXFTFXDXYMXWXRQAPGKGLEWXXXXRNXXXXXXXX 61
||| ||||||| || |||||| | ||| | || | |||||||||| ||
Db 2 VQLVESGGGLVQPGRSLRLSCTASEFTFTDYYMTWVRQAPGKGLEWLGFIRNRANAYTTE 61
Qy 62 YXXSVKGRFTISRDXXKXXXYLQMNSLXXEDTAXYYCXRVSNWXFDYWGQGTXXTVSS 119
| ||||||||||| | ||||||| |||| ||| ||||| |||||||| ||||
Db 62 YAASVKGRFTISRDNSKSILYLQMNSLKTEDTAVYYCARVSNWAFDYWGQGTLVTVSS 119
RESULT 1 from 9.rag database.
BEW79405
(NOTE: this sequence has 4 duplicates in the database searched.
See complete list at the end of this report)
ID BEW79405 standard; protein; 119 AA.
XX
AC BEW79405;
XX
DT 08-MAR-2018 (first entry)
XX
DE Humanized anti-OAcGD2 antibody heavy chain variable region, SEQ 4.
XX
KW OAcGD2 protein; antibody therapy; cancer; cytostatic; diagnostic test;
KW glioma; heavy chain variable region; humanized antibody; neuroblastoma;
KW neuroprotective; ophthalmological; prophylactic to disease;
KW retinoblastoma; therapeutic; tumor marker.
XX
OS Mus musculus.
OS Synthetic.
XX
CC PN EP3269739-A1.
XX
CC PD 17-JAN-2018.
XX
CC PF 15-JUL-2016; 2016EP-00001564.
XX
PR 15-JUL-2016; 2016EP-00001564.
XX
CC PA (OGDT-) OGD2 PHARMA.
XX
CC PI Terme M, Le Doussal J, Dorvillius M, Assouline B;
XX
DR WPI; 2018-04937Q/08.
XX
CC PT New humanized antibody against O-acetylated GD2 ganglioside (OAcGD2),
CC PT useful for preventing and/or treating cancer expressing the OAcGD2
CC PT ganglioside, e.g. neuroblastoma, glioma, and retinoblastoma.
XX
CC PS Example; SEQ ID NO 4; 122pp; English.
XX
CC The present invention relates to a novel humanized antibody against O-
CC acetylated GD2 ganglioside (OAcGD2) useful for preventing and/or treating
CC cancer. The invention further relates to: (1) a method for diagnosing a
CC cancer expressing the OAcGD2 ganglioside in a subject; and (2) a kit for
CC diagnosing a cancer expressing the OAcGD2 ganglioside in a subject. The
CC cancer chosen from neuroblastoma, glioma, retinoblastoma. The present
CC sequence is a humanized anti-OAcGD2 antibody heavy chain variable region,
CC used in the invention for preventing and/or treating cancer.
XX
SQ Sequence 119 AA;
Query Match 100.0%; Score 636; Length 119;
Best Local Similarity 100.0%;
Matches 119; Conservative 0; Mismatches 0; Indels 0; Gaps 0;
Qy 1 EVQLVESGGGLVQPGRSLRLSCTTSEFTFTDYYMTWVRQAPGKGLEWLGFIRNRANGYTT 60
||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 1 EVQLVESGGGLVQPGRSLRLSCTTSEFTFTDYYMTWVRQAPGKGLEWLGFIRNRANGYTT 60
Qy 61 EYNPSVKGRFTISRDNSKSILYLQMNSLKTEDTAVYYCARVSNWAFDYWGQGTLVTVSS 119
|||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Db 61 EYNPSVKGRFTISRDNSKSILYLQMNSLKTEDTAVYYCARVSNWAFDYWGQGTLVTVSS 119
8. The rejection of claim(s) 28 under 35 U.S.C. 103 as being unpatentable Nguyen et al. (Cancer Immunology, Immunotherapy 67: 615-626, 2018) and further in view of Terme et al., European Patent Application, EP 3269739 A1 (published 17 January 2018/ Foreign Patent Document #2 submitted October 13, 2023) and Sanchez-Correa et al. (Cancer Immunology, Immunotherapy 68: 861-870, 2019) is .
Initially, Applicant recites claim 28, see Remarks, submitted July 7, 2026, pages 9 and 10. Following are arguments, “ Nguyen discloses the combination of anti-GD2 antibody and IL-2 treatments for promoting the ADCC capacity of NK cells on neuroblastoma cells in vitro (Figure 3). In the experiments, this combination is shown to be efficient on neuroblastoma cells previously cultured in the presence of all-trans retinoic acid (Figure 5).
However, Nguyen is silent on PD1 or PD-L1, much less suggests that adding an anti-PD1 or anti-PD-L1 compound to said combination for promoting NK cell functions such as ADCC.
Moreover, Nguyen does not disclose OAcGD2 or any anti-OAcGD2 compound, much less suggests that combining retinoic acid and an anti-OAcGD2 compound for promoting NK cell cytotoxicity.
Thus, one of ordinary skill in the art would not have been motivated by Nguyen to combine an anti-OAcGD2 compound with retinoic acid and an anti-PD1 or anti-PD-L1 compound for treating cancer.
Regarding Terme, again, Terme discloses anti-OAcGD2 antibodies comprising the VH/VL sequences recited in claim 23. However, Terme is silent on any anti-PD1 or anti-PD-L1 compound, much less suggests that said anti-OAcGD2 antibodies would have a technical effect in combination with retinoic acid plus an anti-PD1 or anti-PD-L1 compound for promoting NK cell cytotoxicity.
Moreover, Terme does not disclose any effect of said anti-OAcGD2 antibodies on NK cell cytotoxicity. Thus, Terme does not remedy the deficiency of Nguyen.
Turning to Sanchez-Correa, Sanchez-Correa discloses that anti-PD-L1 therapy improves anti-tumor efficacy of NK cell-based immunotherapy.
However, Sanchez-Correa is silent on retinoic acid. Further, similarly to Nguyen, Sanchez- Correa is silent on OAcGD2 or any anti-OAcGD2 compound, much less suggests combining retinoic acid and an anti-OAcGD2 compound for promoting NK cell cytotoxicity. Thus, Sanchez- Correa does not remedy the deficiency of Nguyen, even in combination with Terme.
It follows that one of ordinary skill in the art would not have been motivated by Nguyen, Terme, and Sanchez-Correa with a reasonable expectation of success to combine a therapeutically effective amount of allogenic NK cells treated with retinoic acid, an anti-OAcGD2 compound with retinoic acid, and an anti-PD1 or anti-PD-L1 compound for treating cancer. In other words, an attempt to bring in the isolated teaching from Nguyen, Terme, and Sanchez-Correa would amount to improperly picking and choosing features from different references without regard to the teachings of the references as a whole. While the required evidence of motivation to combine need not come from the applied references themselves, the evidence must come from somewhere within the record. In this case, there is nothing in the record supporting the Office Action's proposed combination.”, see Remarks spanning pages 9 and 10.
Applicant’s arguments and figure have been carefully considered, but the arguments have not been found persuasive.
Foremost, there is no Figure 5 of record in the instant application. And while Applicant asserts “there is nothing in the record supporting the Office Action's proposed combination” that is not true. The last paragraph of the instant rejection makes clear the rationale of why the combination of references teach the claimed invention. To arrive at a proper determination under 35 U.S.C. 103, the Examiner must undertake the role of the person of ordinary skill in the art utilizing factual information and arriving at a legal conclusion based on the facts, devoid impermissible hindsight and rationale for making a proper case of prima facie of obviousness. The Examiner has provided articulated reasoning with rational underpinning to support the legal conclusion of obviousness.
The Examiner points to specific disclosures in the prior art that describe the
limitations of Applicant’s claimed invention. The Examiner’s obviousness conclusion is
based on sufficiently articulated reasoning that overcomes any concerns about
hindsight bias. See KSR, 550 U.S. at 418. In summary, there must be some suggestion or motivation; a reasonable expectation of success; and the prior art references must teach or suggest all the claim limitations.
Teachings amongst other embodiments do not preclude those teachings from
reading on the claim limitations. “[W]hen the species is clearly named, the species
claim is anticipated no matter how many other species are additionally named”, see
Ex parte A, 17 USPQ2d 1716 (Bd. Pat. App. & Inter. 1990).
Moreover, it must be recognized that any judgment on obviousness is in a
sense necessarily a reconstruction based upon hindsight reasoning. But so long as it
takes into account only knowledge which was within the level of ordinary skill at the
time the claimed invention was made, and does not include knowledge gleaned only
from the applicant's disclosure, such a reconstruction is proper. See In re McLaughlin,
443 F.2d 1392,170 USPQ 209 (CCPA 1971).
For the reasons cited herein, the rejection is maintained and made for the
reasons of record and cited herein.
Nguyen teaches allogenic killer (NK) cells exposed to interleukin (IL)-2 are able to enhance NK cell function during adoptive transfer of said cells, see Abstract; sentence bridging pages 619 and 620. The NK cells were also exposed to the anti-GD2 antibody and all-trans retinoic acid, see Abstract; and Figure 2 on page 620.
Nguyen does not teach the treated allogenic NK cells were treated with an anti-O-acetylated disialoganglioside (OAcGD2) compound and with an anti-PD1 or anti-PD-L1 compound.
However, Terme teaches an anti-OAcGD2 antibody compound, see page 2, sections 0006 and 0007. Terme teaches the OAcGD2 ganglioside is expressed by neuroblastoma, as well as breast cancer and small cell lung cancer, see page 8, sections 0065; and page 9, sections 0073 and 0077.
Moreover, Sanchez-Correa teaches in an “… experimental model the use of activated NK cells, that secrete high amounts of IFN-γ in combination with anti-PD-L1 significantly improves anti-tumour efficacy of NK cell-based adoptive immunotherapy, supporting the use of anti-PD-L1 in combination with NK cell therapy regardless of initial tumour PD-L1 status and indicate that NK cell therapy would likely augment the applicability of anti-PD-L1 treatment.”, see page 866, 2nd column (col.).
It would have been obvious to one of ordinary skill in the art at the
effective filing date of the claimed invention to substitute the anti-GD2 antibody of Nguyen with the anti-OAcGD2 antibody of Terme, as well as add an anti-PD-L1 when culturing NK cells in order to enhance NK cell-mediated cytotoxicity against neuroblastoma cells, augment ADCC, increase NK function in cancer patients and improve NK cell-based immunotherapy for patients with neuroblastoma, see last sentence of Nguyen and entire document; and Sanchez-Correa abstract, Conclusion and entire document.
One of ordinary skill in the art would have been motivated to do so
with a reasonable expectation of success by teachings in Nguyen and Terme that these antibodies both target neuroblastoma cells that express their respective antigens, see both references in their entirety. And Nguyen teaches differentiation with all-trans retinoic acid stabilized GD2 expression on tumor cells and enhanced ADCC as well. It would reasonably follow that the all-trans retinoic acid would have the same effect on OAcGD2 expression on neuroblastoma cells. And Sanchez-Correa teaches with the addition of an anti-PD-L1 when culturing NK cells has evidenced “[a]nti-PD-1/anti-PD-L1 therapies have shown success in the treatment of some types of cancer, mainly in those expressing PD-L1 and with lymphocyte infiltration…PD-1 or PD-L1 blockade is associated with prolonged overall survival in PD-L1-positive and PD-L1-negative patients. The long-term clinical benefits are observed independently of the interventional agent, cancer histotype, method of randomization stratification, type of immunohistochemical scoring system, drug target, type of control group, and median follow-up time.”, see Sanchez-Correa, page 866, 1st col., 2nd paragraph (para.).
Conclusion
9. 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.
10. Any inquiry concerning this communication or earlier communications from the Examiner should be directed to ALANA HARRIS DENT whose telephone number is (571)272-0831. The Examiner works a flexible schedule, however can generally be reached between 8AM-8PM, Monday through Friday.
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, Julie Wu can be reached at 571-272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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ALANA HARRIS DENT
Primary Examiner
Art Unit 1643
18 September 2026
/Alana Harris Dent/Primary Examiner, Art Unit 1643
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