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 16-30 are pending.
Claims 23 and 24 have been amended.
Claims 16-30 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Withdrawn Rejection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112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement is withdrawn in light of the amendments to the claims, deleting recitations, "a sequence having a percentage of identity of at least 85% with SEQ ID NO: 8" and "a variant thereof.", see Remarks submitted June 30, 2026, page 6, 4th paragraph.
Maintained Grounds of Rejection
Claim Rejections - 35 USC § 102
5. The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
6. The rejection of claim(s) 16-19, 22 and 28-30 under 35 U.S.C. 102(a)(1) as being anticipated by Gibbs et al., US 2020/0369767 (published November 26, 2020) is maintained.
Applicant asserts “the cited prior art fails to teach or suggest every feature recited in Applicant’s claims”, see Remarks submitted June 30, 2026, page 7, 6th paragraph (para.). Specifically, Applicant argues “Gibbs discloses a method of ablating hematopoietic stem cells in a patient comprising administering to the patient an immunotherapeutic agent binding to c-kit and an immunotherapeutic agent binding to CD47 or SIRP-alpha.
Gibbs further teaches that the immunotherapeutic agent of the invention, for instance, a mono- or multispecific antibody, may bind to a tumor-associated antigen selected from a very long list that includes OAcGD2 (paragraph 83, page [12]). However, there is no example of said antibody.
In addition, Gibbs discloses the possible combination of the above-described hematopoietic stem cell ablation with "agents effective to treat cancer" (paragraph 85 [on page 12] and claim 35 [on page 41]), such as a chemotherapeutic agent (claim 37 [on page 42]). Retinoic acid is recited in Gibbs as an example of a chemotherapeutic agent but never mentioned in combination.
Gibbs, however, does not explicitly disclose the specific combination of an anti-OAcGD2 compound with an anti-CD47 or anti-SIRP-alpha compound.”, see page 7 of the Remarks, paragraphs (paras.) 2-5.
Applicant’s arguments and the pointed out passages within the prior art have been carefully considered, but the arguments have not been found persuasive.
Foremost, “[w]hen the reference relied on expressly anticipates or makes obvious all of the elements of the claimed invention, the reference is presumed to be operable. Once such a reference is found, the burden is on applicant to rebut the presumption of operability. In re Sasse, 629 F.2d 675, 207 USPQ 107 (CCPA 1980). See also MPEP § 716.07. See also In re Antor Media Corp., 689 F.3d 1282, 103 USPQ2d 1555 (Fed. Cir. 2012), wherein prior art printed publications, like prior art patents are presumptively enabled barring any contrary showing by applicant or patentee and burden shifts to applicant to submit rebuttal evidence of nonenablement.
Moreover, the retinoic acid is cited as a co-therapy, effective to treat cancer and used in combination “…with an immunotherapeutic agent specifically binding…an immunotherapeutic agent specifically binding to CD47 or SIRPa…in further combination with one or more agents effective to deplete other cells of the immune system”, see page 9, sections 0071 and 0072; and segment V. beginning on page 12, sections 0085 and 0087 (2nd column, 6th line). Hence, the therapeutic agents are mentioned in combination and the rejection is maintained.
Gibbs discloses methods of co-administration regimes including an “… immunotherapeutic agent specifically binding to CD47 is an antibody specifically binding to CD47” or “the immunotherapeutic agent specifically binding to SIRPα is an antibody” with an “immunotherapeutic agent that binds an o-acetyl-GD2 ganglioside (OAcGD2)”, as well as an additional anticancer agent to treat ablation of HSPCs, as well as solid cancers (i.e. breast cancer and small cell lung cancer (SCLC)), see abstract; page 1, sections 0005; 0009 and 0010; page 2, sections 0013 and 0015; page 11, section 0082, 2nd column (col.); page 12, section 0085; sections 0118 and 0119 spanning page 16 and 17; page 17, section 0128; and page 20, section 0155.
The immunotherapeutic agent that binds OAcGD2 is a T cell receptor (TCR) or chimeric antigen receptor (CAR) antigen binding domain or the immunotherapeutic agent described herein (e.g., monospecific or multi-specific antibody or antigen-binding fragment thereof or antibody mimetic) than binds a tumor-associated antigen (TAA), such as ganglioside G2 (GD2) and OAcGD2, see page 11, section 0082; and page 14, 1st col., 10 lines from the bottom. The disclosed antibody may be a humanized antibody, see sections 0134 and 0135 spanning pages 17 and 18.
The immunotherapeutic agents administered as pharmaceutical compositions may be administered alone or in combination with other ingredients, thereby reading on simultaneously, see page 3, section 0038.
The disclosed combination of immunotherapeutic agents, CD47 antibody or SIRPa antibody with the OAcGD2 antibody may further include chemotherapeutic agents, “retinoids such as retinoic acid”, see segment V. beginning on page 12, particularly, page 13, 2nd col., line 6.
Claim Rejections - 35 USC § 103
7. 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.
8. The rejection of claim(s) 18-30 under 35 U.S.C. 103 as being unpatentable over Gibbs et al., US 2020/0369767 (published November 26, 2020), and further in view of Terme et al., European Patent Application, EP 3269739 A1 (published 17 January 2018) and Barbas, III, US 2014/0127200 A1 (published May 8, 2014) is maintained.
Applicant argues they have “…surprisingly demonstrated that the anti-SIRP-alpha antibody P84 unexpectedly increased macrophage-mediated phagocytosis of cancer cells opsonized with the anti-OAcGD2 antibody 8B6 (Figure 3D of the specification as filed)…, neither the anti-SIRP-alpha antibody nor the anti-OAcGD2 antibody promotes cancer cell phagocytosis when used alone, which shows an unexpected synergistic effect of an anti-SIRP-alpha antibody with an anti-OAcGD2 antibody in promoting phagocytosis of cancer cells.
Moreover, Applicants [show] a superior anti-tumor effect in vivo with the combination of 8B6 and P84 antibodies as compared to 8B6 and P84 monotherapies.”, see Remarks submitted June 30, 2026, page 8, 1st and 2nd paragraphs (paras.).
Applicant’s arguments directed toward primary reference, Gibbs have been presented in the pending 102 rejection herein in segment 6 beginning on page 3; and in the Remarks, page 8, paras. 3-5. The Gibbs reference does not fall.
In conclusion, Applicant argues secondary references, Terme and Barbas III “do not provide the motivation to perform the proposed modification of Gibbs” and do not remedy the alleged deficiencies of Gibbs, see page 9, paras. 1-3. “Without such motivation and absent improper hindsight reconstruction, a person of ordinary skill in the art would not be motivated to perform the proposed modification, and claim 18 is believed to be non-obvious and patentable over the applied prior art.”, see para. bridging pages 9 and 10 of the Remarks.
Applicant’s arguments and points of view have been carefully considered, but fail to persuade.
“[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, Applicants have not provided evidence that these results are unexpected.
And addressing Applicant’s concerns regarding hindsight, rather than using hindsight, 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.
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).
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.
Gibbs teaches methods of co-administration regimes including an “… immunotherapeutic agent specifically binding to CD47 is an antibody specifically binding to CD47” or “the immunotherapeutic agent specifically binding to SIRPα is an antibody” with an “immunotherapeutic agent that binds an o-acetyl-GD2 ganglioside (OAcGD2)”, as well as an additional anticancer agent to treat ablation of HSPCs, as well as solid cancers (i.e. breast cancer and small cell lung cancer (SCLC)), see abstract; page 1, sections 0005; 0009 and 0010; page 2, sections 0013 and 0015; page 11, section 0082, 2nd column (col.); page 12, section 0085; sections 0118 and 0119 spanning page 16 and 17; page 17, section 0128; and page 20, section 0155.
The immunotherapeutic agent that binds OAcGD2 is a T cell receptor (TCR) or chimeric antigen receptor (CAR) antigen binding domain or the immunotherapeutic agent described herein (e.g., monospecific or multi-specific antibody or antigen-binding fragment thereof or antibody mimetic) than binds a tumor-associated antigen (TAA), such as ganglioside G2 (GD2) and OAcGD2, see page 11, section 0082; and page 14, 1st col., 10 lines from the bottom. The taught antibody may be a humanized antibody, see sections 0134 and 0135 spanning pages 17 and 18.
The immunotherapeutic agents administered as pharmaceutical compositions may be administered alone or in combination with other ingredients, thereby reading on simultaneously, see page 3, section 0038. The taught combination of immunotherapeutic agents, CD47 antibody or SIRPa antibody with the OAcGD2 antibody may further include chemotherapeutic agents, “retinoids such as retinoic acid”, see segment V. beginning on page 12, particularly, page 13, 2nd col., line 6.
Gibbs does not teach the anti-OAcGD2 antibody compound that comprises complementary-determining regions (CDRs) set forth in claim 21 and the light chain variable region (VL) is sequence identical with Applicant’s SEQ ID NO: 7 and the heavy chain variable region (VH) is sequence identical with Applicant’s SEQ ID NO: 8, nor the cancer treated by the said antibody compound in combination with the additional antibodies is neuroblastoma, wherein the combination of antibodies can be administered sequentially, separately but simultaneously, see page 23, section 0276.
Gibbs does not teach the anti-OAcGD2 compound is bispecific and tetravalent comprising at least two antigen binding sites directed to OacGD2 and at least one antigen directed to SIRPa or CD47.
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 and light chain variable region (VL) sequences, SEQ ID NO: 13, SEQ ID NO: 14,.
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-OAcGD2 antibody of Gibbs 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 and either, SIRPa or CD47 as presented in the art.
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.
Additionally, Barbas, III teaches therapeutic compositions comprising multispecific and/or multivalent molecule that target two or more cancer targets simultaneously to treat cancer, see Figures 1 and 2; page 1, section 0012; page 4, section 0031; sections 0065-0067 spanning pages 6 and 7; page 10, section 0127; and page 19, sections 0225, 0227.
It would have been obvious to one of ordinary skill in the art at the effective filing date of the claimed invention to manufacture bispecific tetravalent antibodies with modular recognition domains (MRDs) able to target the antibodies to OAcGD2 and SIRPa or CD47 to treat cancer, see abstract 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 Barbas, III that this technology and method of making antibodies containing one or MDRs will have “…superior drug properties with substantially reduced production costs as compared to conventional bispecific antibodies and combinations of monoclonal antibodies.”, see page 4, section 0032.
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
September 8, 2026
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