DETAILED ACTION
Continued Examination Under 37 CFR 1.114
1. 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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 3/30/2026 has been entered.
2. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
3. New claims 26-29 have been added. Claims 10-13, 15, 17, 22 and 25-29 are pending. Claims 1-9, 14, 16, 18-21 and 23-24 are canceled. Claims 10-12, 22 and 25 have been amended.
4. Claims 10-13, 15, 17, 22 and 25-29 are under examination.
Objections Withdrawn
5. All claim objections in the Final Action mailed on 12/29/2025 are withdrawn in view of applicant’s amendments.
Rejections Withdrawn
6. The rejection of claims 2-5 under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends is withdrawn in view of applicant’s cancellation of the claims.
Rejections Maintained
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. Claims 10-13, 15, 17, 22, 25 and new claim 26-29 remain/are rejected under 35 U.S.C. 103 as being unpatentable over Harrington et al. (British J Cancer, 2016, 114: 417-426, IDS filed on 5/5/2022), in view of Burgess (US 2007/0009543A1, pub. date: 1/11/2007).
Regarding claims 10, 12, 22 and new claim 28, Harrington et al. teaches an anti-CDCP1 antibody 10D7 previously described by Deryugina et al. 2009 (page 419, column 2, para 3). The antibody 10D7 is the 10D7 antibody disclosed in the instant specification (see page 51, lines 17-21, reproduced above). The antibody 10D7 inherently comprises the CDR sequences (SEQ ID NOs: 4-9) of claims 10-12 and 22, and the VH and VL sequences (SEQ ID NOs: 2 and 3) of claim 28, as evidenced by the instant specification (see page 51, lines 17-21 and page 23, lines 10-30, reproduced below).
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The limitation “upon binding to CDCP1, the antibody-CDCP1 complex or antigen-binding fragment-CDCP1 complex is internalized” is considered as an inherent property of antibody 10D7, as evidenced by the instant specification (Example 5).
Regarding claim 15, Harrington discloses a composition comprising 10D7 antibody and media (a pharmaceutically acceptable carrier) (page 419, column 1, para 4), and a composition comprising the 10D7 antibody and at least water for administration (page 419, column 2, para 3).
Regarding claim 26, the antibody 10D7 inherently binds to the cleaved CDCP1 receptor or the uncleaved CDCP1 receptor, as evidenced by the instant specification (last sentence of Example 10: intact and cleaved CDCP1 can be functionally targeted with antibody 10D7 in PDAC cells. Thus, antibody 10D7 is effective at targeting uncleaved as well as cleaved CDCP1 that are present on the surface of cancer cells.).
Regarding claim 27, the antibody 10D7 inherently improves the efficacy of chemotherapy compared to administration of the chemotherapy alone.
Regarding claims 11-13, Harrington teaches a cytotoxin-conjugated chimeric mouse anti-CDCP1 antibody was effective at reducing subcutaneous tumor growth and lymph-node dissemination of prostate cancer PC3 cells (page 418, column 1, para 2).
However, Harrington does not teach a cytotoxin-conjugated 10D7 antibody.
Regarding claims 10, 22 and 25, Harrington does not teach that the anti-CDCP1 10D7 antibody is conjugated to a radionuclide, and the radionuclide is 111In or 90Y.
Regarding claim 29, Harrington does not teach that the antibody comprises human heavy and light chain constant region sequences.
Burgess teaches that anti-CDCP1 antibodies can be conjugated to a therapeutic agent, such as a cytotoxic agent, a radionuclide or drug moiety ([0015]), and the radionuclide is 111In or 90Y ([0017]). Burgess also teaches making chimeric and humanized anti-CDCP1 antibodies ([0034] and [0036]). Chimeric and humanized antibody comprise human heavy and light chain constant regions.
It would have been prima facie obvious to one of ordinary skill in the art at the time the invention was made to have conjugated the 10D7 antibody to a cytotoxic agent or a radionuclide such as 111In or 90Y in view of Harrington and Burgess. One would have been motivated to do so with a reasonable expectation of success because Harrington teaches that a cytotoxin-conjugated chimeric mouse anti-CDCP1 antibody was effective at reducing subcutaneous tumor growth and lymph-node dissemination of prostate cancer PC3 cells (page 418, column 1, para 2), targeting of CDCP1 by the antibody 10D7 impedes high-grade serous ovarian cancer (HGSC) PDX (patient derived xenograft) growth in vivo (page 423 and Fig. 6), and Burgess teaches that anti-CDCP1 antibodies can be conjugated to a therapeutic agent, such as a cytotoxic agent, a radionuclide or drug moiety ([0015]), wherein the anti-CDCP1 antibodies are humanized or chimeric ([0034] and [0036). Note that humanized or chimeric antibody comprises human heavy and light chain constant region sequences. A radionuclide such as 111In or 90Y can be used either as a detecting agent or a cytotoxic agent.
Regarding claim 17, Harrington et al. further teaches detecting CDCP1 in tissue sample of patients by immunohistochemistry using a rabbit anti-CDCP1 antibody (page 418, column 2 and Fig. 6A). However, Harrington et al does not teach detecting CDCP1-expressing cancer cell in tissue sample of patients by immunohistochemistry using the antibody 10D7.
Burgess et al. teaches that an anti-CDCP1 antibody can be used in a method for screening for or diagnosis of ovarian cancer in a subject ([0119]), the method comprising contacting a biological sample of human tissue with an anti-CDCP1 antibody ([0119], [0128]) and [0129]).
It would have been prima facie obvious to one of ordinary skill in the art before the effective filing date of the claimed invention to have used the antibody 10D7 for detection of CDCP1-exrpessing cancer cell in view of Harrington and Burgess. One of ordinary skill in the art would have been motivated to do so with a reasonable expectation of success because the substitution of one known element (the anti-CDCP1 antibody 10D7) for another (another anti-CDCP1 antibody) would have yielded predictable results in detecting CDCP1 expressing cancer cells to one of ordinary skill in the art at the time of invention.
Argument A
The Examiner's Inherency Point Does Not Resolve the Relevant Expectedness Questions
The Office Action states that the internalization limitation is "an inherent property of the antibody 10D7" based on Applicants' own specification. That point does not resolve the distinct expectedness questions presented here, which arise in two discrete contexts: (1) the requirement for a prima facia case of obviousness to present a reasonable expectation of success regarding what claimed (here, now, the functionality of internalization); and (2) the use of evidence of unexpected superior results to rebut any prima facia case of obviousness that may have been made.
As the Federal Circuit has explained, "[w]hat is important regarding properties that may be inherent, but unknown, is whether they are unexpected. All properties of a composition are inherent in that composition, but unexpected properties may cause what may appear to be an obvious composition to be nonobvious." Honeywell Int'lInc. v. Mexichem Amanco HoldingSA. de C.V, 865 F.3d 1348, 1355-56 (Fed. Cir. 2017). Thus, even if internalization is now shown to be a property of Applicants' 1OD7-based constructs, that does not establish that the cited art taught or made reasonably expected (in either context noted above) the now- claimed internalization feature.
Here, the relevant question for the reasonable-expectation-of-success prong is not whether internalization, once later discovered, may be characterized as inherent. The question is whether a person of ordinary skill in the art, starting from Harrington and Burgess, would have had a reasonable expectation of successfully achieving what is now explicitly claimed - namely, 1OD7-based conjugates and labeled constructs that, upon binding to CDCP1, internalize the bound antibody-CDCP1 complex. The Office does not identify any teaching in Harrington or Burgess that would have supplied that expectation. Instead, the Office points only to Applicants' own specification to show that Applicants later demonstrated the property. That does not satisfy the Office's burden on reasonable expectation of success, and it likewise does not answer the separate question whether the demonstrated internalization property and its practical significance were unexpected.
Response to Argument A
Applicant’s arguments have been carefully considered but are not persuasive. It is undisputed that the antibody 10D7 of the prior art (Harrington) is structurally identical to the claimed antibody. Therefore, the antibody 10D7 of the prior art would inherently have the property “upon binding to CDCP1, the antibody-CDCP1 complex or antigen-binding fragment-CDCP1 complex is internalized”.
MPEP 2112 states “Where applicant claims a composition in terms of a function, property or characteristic and the composition of the prior art is the same as that of the claim but the function is not explicitly disclosed by the reference, the examiner may make a rejection under both 35 U.S.C. 102 and 103. "There is nothing inconsistent in concurrent rejections for obviousness under 35 U.S.C. 103 and for anticipation under 35 U.S.C. 102." In re Best, 562 F.2d 1252, 1255 n.4, 195 USPQ 430, 433 n.4 (CCPA 1977). This same rationale should also apply to product, apparatus, and process claims claimed in terms of function, property or characteristic.”
It appears that applicant’s argument that there was no reasonable expectation of success relates to discovering the inherent property. This is not found persuasive.
MPEP 2112 states "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977). In In re Crish, 393 F.3d 1253, 1258, 73 USPQ2d 1364, 1368 (Fed. Cir. 2004), the court held that the claimed promoter sequence obtained by sequencing a prior art plasmid that was not previously sequenced was anticipated by the prior art plasmid which necessarily possessed the same DNA sequence as the claimed oligonucleotides. The court stated that "just as the discovery of properties of a known material does not make it novel, the identification and characterization of a prior art material also does not make it novel." Id.
The only difference between Harrington and independent claims is Harrington does not teach the antibody 10D7 is conjugated to a cytotoxic agent or a detectable label. However methods of making antibody conjugates were well known in the art before the effectively filing date of the instant invention, as evidenced by the cited references. Harrington teaches a cytotoxin-conjugated chimeric mouse anti-CDCP1 antibody (page 418, column 1, para 2). Burgess teaches that anti-CDCP1 antibodies can be conjugated to a therapeutic agent, such as a cytotoxic agent, a radionuclide or drug moiety ([0015]). Therefore, one would have had a reasonable expectation of succuss to make a 10D7 conjugate.
Argument B
Harrington Does Not Teach or Suggest That 10D7 Internalizes CDCP1
Professor Hooper explains that delivery of a conjugated antibody into a cell depends on internalization of the targeted cell-surface antigen bound to the antibody, but that there can be no generalization that all cell-surface-binding antibodies-even antagonistic antibodies-cause internalization. Hooper Decl. 12. He further explains that Harrington did not probe the mechanism of action of 10D7 beyond its ability to reduce CDCP1-mediated signaling via Src, and did not include any experiment designed to determine whether 10D7 binding causes internalization of CDCP1. Id. 14(a)-(b).
That testimony is consistent with the scientific context known in the art. As discussed in the Hooper Declaration and in Cesar et al., 10D7 was understood as a cleavage-blocking antibody acting at the cell surface to prevent CDCP1 cleavage and the downstream survival signaling that follows. Hooper Decl. 14(b)-(c). The art therefore did not direct the skilled person to infer that 10D7 functioned through internalization, or that internalization was required for 10D7's known functional- blocking activity. Accordingly, even if Harrington supplied some motivation to continue studying CDCP1-targeted therapeutics, Harrington did not teach, suggest, or render reasonably predictable that 10D7 would internalize CDCP1 upon binding, much less that a 1OD7-based conjugate or labeled construct would retain that behavior and successfully deliver a payload.
Response to Argument B
Applicant’s arguments, the Declaration of John Hooper and Casar et al have been carefully considered but are not persuasive. It is true that one cannot predict if a given antibody internalizes or not without testing. However, in the instant case, the prior art antibody 10D7 is identical to the instant antibody. Any properties of the instant antibody are inherent property of prior art 10D7.
Argument C.
The Prior Art Does Not Permit a Credible Extrapolation from Other Anti- CDCP1 Antibodies to 10D7
The Examiner's reasoning depends on extrapolating from Siva's 25A11 antibody and from Burgess's polyclonal anti-CDCP1 antibodies to the specific monoclonal 10D7 antibody now recited by CDR sequence. The record does not support that extrapolation.
Professor Hooper explains that Siva did not elucidate a mechanism of action for 25A11 that would permit comparison to 10D7. Hooper Decl. 15(a). Siva reported an internalizing 25A11-cytotoxin construct, but did not show that naked 25A11 had
the same functional properties as naked 10D7. Id. Indeed, Siva further suggested naked anti-CDCP1 antibodies as less toxic alternatives to cytotoxin-conjugated approaches. Id. 15(b)-(d). Thus, Siva does not provide a basis to conclude that 25A11 and 10D7 bind CDCP1 similarly, function similarly, or could be expected to behave similarly when conjugated. Burgess likewise does not fill the gap. As Professor Hooper explains, the internalization result reported in Burgess concerns a polyclonal antibody mixture. Hooper Decl. 20. Internalization observed for a mixture of many antibodies cannot reasonably be extrapolated to any particular monoclonal antibody, let alone the sequence-defined 10D7 antibody recited in the amended claims. Nor does Burgess disclose data showing that its polyclonal antibody had the therapeutic or cancer-cell- killing functionality on which the Examiner's extrapolation depends. Id.
Response to Argument C
Applicant’s arguments and the Declaration have been carefully considered but are not persuasive. The examiner did not compare and/or extrapolate the property of the antibody of Siva or Burgess to the antibody 10D7. Burgess is cited to teach making an antibody conjugate.
Argument D
The Cited Art Fails To Establish a Reasonable Expectation of Success
The relevant success here is not merely making a chimera or attaching a label or payload. The relevant success is successfully achieving the claimed 10D7-based construct with the recited internalization function. See Hooper Decl. 7. Whether that function may be described as inherent is immaterial to that ex ante expectedness inquiry: what may be inherent is not necessarily known or reasonably predicted. Honeywell, 865 F.3d at 1355-56. Known methods for chimerization or conjugation therefore do not establish that the specific 10D7-based conjugates and labeled agents now claimed would have retained the binding, internalization, trafficking, and payload-delivery behavior required by the amended claims. OSI Pharmaceuticals confirms that, particularly in the cancer-therapeutics context, the law requires more than speculation or hindsight optimism. See OSI Pharms., LLC v. Apotex Inc., 939 F.3d 1375, 1384-85 (Fed. Cir. 2019). Here, the Hooper Declaration directly addresses the state of the art and explains why a skilled person would not have extrapolated from Siva or Burgess to conclude that 10D7 would internalize CDCP1 and function as a useful payload carrier.
For the same reasons, claim 17 is not rendered obvious by the Examiner's generic substitution rationale. Claim 17 incorporates the antibody of claim 10, which is not a generic anti-CDCP1 antibody but a specific sequence-defined, labeled 10D7- based construct now further limited by the internalization requirement. Neither Harrington nor Burgess teaches using that specific construct for the claimed detection method, and the cited art does not provide a reasonable expectation of success in doing so.
Response to Argument D
Applicant’s arguments have been carefully considered but are not persuasive. Independent claims have been amended to recite “ wherein, upon binding to CDCP1, the antibody-CDCP1 complex or antigen-binding fragment-CDCP1 complex is internalized”. The claims do not specifically recite “upon binding to CDCP1, the antibody conjugate is internalized”.
It appears that applicant argued that conjugation might affect the antibody function including internalization. This is not persuasive. The methods of making antibody conjugates while maintaining the antibodies’ function including antigen binding affinity, epitope recognition and internalization were well known in the art. This principle is the basis of many successful antibody-drug conjugates (ADCs), wherein the conjugated antibody binds the target and is then internalized into the cell. Although large payloads may affect internalization, they are not recited in the claims. The claims encompass an antibody 10D7 conjugated to a small detectable label, or a small cytotoxic agent such as a radioisotope. Such antibody conjugate is expected by one of ordinary skill in the art to retain the internalizing ability of antibody 10D7. This is further evidenced by Braslawsky et al. (Cancer Immunol Immunother, 1991, 33:367-374). Braslawsky et al. shows that immunoconjugates prepared from internalizing antibody G28.1 are capable of internalizing after binding to cell-surface antigens (page 371, last paragraph).
Argument E
The Record Independently Establishes Unexpected Superior Results
Even assuming arguendo that the Office has stated a prima facie case, Applicants' evidence independently rebuts that case. Honeywell explains that "[w]hat is important regarding properties that may be inherent, but unknown, is whether they are unexpected," and that "unexpected properties may cause what may appear to be an obvious composition to be nonobvious." 865 F.3d at 1355-56. In re Soni likewise recognizes that unexpected superior results may establish nonobviousness. 54 F.3d 746, 750-51 (Fed. Cir. 1995). Such evidence is evaluated against the closest specific embodiments in the prior art, or examples that are even closer to what is claimed than the closes specific examples in the prior art. Bristol-Myers Squibb Co. v. Teva Pharms. USA, Inc., 752 F.3d 967, 977 (Fed. Cir. 2014).
Here, the closest specific embodiment in the prior art is, at most, Siva's 25A11 cytotoxin-conjugated antibody and Burgess's polyclonal anti-CDCP1 work. Neither taught or predicted that the specific 10D7 antibody-previously known as a function- blocking, cleavage-blocking antibody-would, upon binding, internalize CDCP1 and thereby provide an effective platform for intracellular payload delivery and in vivo theranostic targeting. Hooper Decl. 12, 14, 15, 17, 19-20.
The unexpected superior result here is not merely a newly proposed mechanism in the abstract. Rather, the record shows a previously unappreciated and practically significant property of the claimed constructs: 10D7 induces rapid clustering and internalization of CDCP1, trafficking of the antibody-receptor complex into acidified intracellular vesicles, degradation of targeted CDCP1, effective in vivo tumor accumulation of radionuclide-labeled 10D7 constructs, and successful intracellular delivery of cytotoxic payloads. See Hooper Decl. 7; see also the specification, Examples 4, 7, 10, and 11.
Because amended claims 10, 11, 12, and 22 now expressly recite the internalization function, and because claims 15, 17, 25, and new claims 26-29 depend from those amended claims, the nexus between the objective evidence and the pending claims is direct. At a minimum, the evidence of unexpected superior and materially beneficial results must be weighed as part of the ultimate obviousness determination, and on this record it compels withdrawal of the rejection.
Response to Argument E
Applicant’s arguments of unexpected results are not persuasive as internalization is an inherent property of antibody 10D7. MPEP 2112 states "[T]he discovery of a previously unappreciated property of a prior art composition, or of a scientific explanation for the prior art’s functioning, does not render the old composition patentably new to the discoverer." Atlas Powder Co. v. IRECO Inc., 190 F.3d 1342, 1347, 51 USPQ2d 1943, 1947 (Fed. Cir. 1999). Thus the claiming of a new use, new function or unknown property which is inherently present in the prior art does not necessarily make the claim patentable. In re Best, 562 F.2d 1252, 1254, 195 USPQ 430, 433 (CCPA 1977).
For the foregoing reasons, the rejection is deemed proper and is therefore maintained.
Conclusion
9. No claims are allowed.
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/HONG SANG/Primary Examiner, Art Unit 1646
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