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 .
Claims Status
The Amendment filed on 03Oct2024 is acknowledged in which claim(s) 2-5, 7-9, 11, 20-22, 24-39, 42-43, 45-51, 54, 56-59, 61-68, and 70-93 were canceled by Applicant.
Applicant’s election without traverse of the following species: a) a VH domain of SEQ ID NO: 65, comprising HCDR1-3 or SEQ ID NOs: 26, 30, and 32, respectively, and b) a VL domain of SEQ ID NO: 62, comprising LCDR1-3 of SEQ ID NOs: 1-3, respectively, in the reply filed on 11Jun2026 is acknowledged.
Claim(s) 1, 6, 10, 12-19, 23, 40-41, 44, 52-53, 55, 60, and 69 is/are presented for examination on the merits.
Nucleotide and/or Amino Acid Sequence Disclosures
REQUIREMENTS FOR PATENT APPLICATIONS CONTAINING NUCLEOTIDE AND/OR AMINO ACID SEQUENCE DISCLOSURES
Items 1) and 2) provide general guidance related to requirements for sequence disclosures.
37 CFR 1.821(c) requires that patent applications which contain disclosures of nucleotide and/or amino acid sequences that fall within the definitions of 37 CFR 1.821(a) must contain a "Sequence Listing," as a separate part of the disclosure, which presents the nucleotide and/or amino acid sequences and associated information using the symbols and format in accordance with the requirements of 37 CFR 1.821 - 1.825. This "Sequence Listing" part of the disclosure may be submitted:
In accordance with 37 CFR 1.821(c)(1) via the USPTO patent electronic filing system (see Section I.1 of the Legal Framework for Patent Electronic System (https://www.uspto.gov/PatentLegalFramework), hereinafter "Legal Framework") as an ASCII text file, together with an incorporation-by-reference of the material in the ASCII text file in a separate paragraph of the specification as required by 37 CFR 1.823(b)(1) identifying:
the name of the ASCII text file;
ii) the date of creation; and
iii) the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(1) on read-only optical disc(s) as permitted by 37 CFR 1.52(e)(1)(ii), labeled according to 37 CFR 1.52(e)(5), with an incorporation-by-reference of the material in the ASCII text file according to 37 CFR 1.52(e)(8) and 37 CFR 1.823(b)(1) in a separate paragraph of the specification identifying:
the name of the ASCII text file;
the date of creation; and
the size of the ASCII text file in bytes;
In accordance with 37 CFR 1.821(c)(2) via the USPTO patent electronic filing system as a PDF file (not recommended); or
In accordance with 37 CFR 1.821(c)(3) on physical sheets of paper (not recommended).
When a “Sequence Listing” has been submitted as a PDF file as in 1(c) above (37 CFR 1.821(c)(2)) or on physical sheets of paper as in 1(d) above (37 CFR 1.821(c)(3)), 37 CFR 1.821(e)(1) requires a computer readable form (CRF) of the “Sequence Listing” in accordance with the requirements of 37 CFR 1.824.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed via the USPTO patent electronic filing system as a PDF, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the PDF copy and the CRF copy (the ASCII text file copy) are identical.
If the "Sequence Listing" required by 37 CFR 1.821(c) is filed on paper or read-only optical disc, then 37 CFR 1.821(e)(1)(ii) or 1.821(e)(2)(ii) requires submission of a statement that the "Sequence Listing" content of the paper or read-only optical disc copy and the CRF are identical.
Specific deficiencies and the required response to this Office Action are as follows:
Specific deficiency – Nucleotide and/or amino acid sequences appearing in the drawings are not identified by sequence identifiers in accordance with 37 CFR 1.821(d) [e.g., Fig. 2C-2F, 8A]. Sequence identifiers for nucleotide and/or amino acid sequences must appear either in the drawings or in the Brief Description of the Drawings.
Required response – Applicant must provide:
Replacement and annotated drawings in accordance with 37 CFR 1.121(d) inserting the required sequence identifiers;
AND/OR
A substitute specification in compliance with 37 CFR 1.52, 1.121(b)(3) and 1.125 inserting the required sequence identifiers into the Brief Description of the Drawings, consisting of:
A copy of the previously-submitted specification, with deletions shown with strikethrough or brackets and insertions shown with underlining (marked-up version);
A copy of the amended specification without markings (clean version); and
A statement that the substitute specification contains no new matter.
Drawings
The drawings is/are objected to because of the following informalities: Fig 4B, 14A, 15B-15C, 16A-16B: Unclear which sample is which in grayscale figures. Appropriate correction is requested.
Specification
The use of trade name(s) or mark(s) used in commerce (e.g., DVD-Ig, nanobody, FlowJo, Prism, GraphPad), has been noted in this application. The term should be accompanied by the generic terminology; furthermore the term should be capitalized wherever it appears or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the term.
Although the use of trade names and marks used in commerce (i.e., trademarks, service marks, certification marks, and collective marks) are permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner which might adversely affect their validity as commercial marks.
The disclosure is objected to because it contains an embedded hyperlink and/or other form of browser-executable code [e.g., ¶ 0707, 0253]. Applicant is required to delete the embedded hyperlink and/or other form of browser-executable code; references to websites should be limited to the top-level domain name without any prefix such as http:// or other browser-executable code. See MPEP § 608.01.
Claim Interpretation
Claim(s) 6, recite(s) “wherein the first cleaved domain consists of the amino acid sequence as set forth in SEQ ID NO: 63, 68, or 74 or the second cleaved domain consists of the amino acid sequence as set forth in SEQ ID NO: 64, 70, or 77”. Based on alignment of the full-length CDCP1 (SEQ ID NO: 273), SEQ ID NOs: 68 and 70 correspond to fragments from a cut at R368 (see alignment below). Therefore, prior art teaching CDCP1 cleavage at residue R368 are considered to teach SEQ ID NOs: 68 and 70.
Alignment of full-length CDCP1 (SEQ ID NO: 273) with cleaved CDCP1 domains (SEQ ID NOs: 68, 70):
CLUSTAL O(1.2.4) multiple sequence alignment
Seq70 ------------------------------------------------------------ 0
Seq68 -----------------------------FEIALPRESNITVLIKLGTPTLLAKPCYIVI 31
Seq273 MAGLNCGVSIALLGVLLLGAARLPRGAEAFEIALPRESNITVLIKLGTPTLLAKPCYIVI 60
Seq70 ------------------------------------------------------------ 0
Seq68 SKRHITMLSIKSGERIVFTFSCQSPENHFVIEIQKNIDCMSGPCPFGEVQLQPSTSLLPT 91
Seq273 SKRHITMLSIKSGERIVFTFSCQSPENHFVIEIQKNIDCMSGPCPFGEVQLQPSTSLLPT 120
Seq70 ------------------------------------------------------------ 0
Seq68 LNRTFIWDVKAHKSIGLELQFSIPRLRQIGPGESCPDGVTHSISGRIDATVVRIGTFCSN 151
Seq273 LNRTFIWDVKAHKSIGLELQFSIPRLRQIGPGESCPDGVTHSISGRIDATVVRIGTFCSN 180
Seq70 ------------------------------------------------------------ 0
Seq68 GTVSRIKMQEGVKMALHLPWFHPRNVSGFSIANRSSIKRLCIIESVFEGEGSATLMSANY 211
Seq273 GTVSRIKMQEGVKMALHLPWFHPRNVSGFSIANRSSIKRLCIIESVFEGEGSATLMSANY 240
Seq70 ------------------------------------------------------------ 0
Seq68 PEGFPEDELMTWQFVVPAHLRASVSFLNFNLSNCERKEERVEYYIPGSTTNPEVFKLEDK 271
Seq273 PEGFPEDELMTWQFVVPAHLRASVSFLNFNLSNCERKEERVEYYIPGSTTNPEVFKLEDK 300
Seq70 ------------------------------------------------------------ 0
Seq68 QPGNMAGNFNLSLQGCDQDAQSPGILRLQFQVLVQHPQNESNKIYVVDLSNERAMSLTIE 331
Seq273 QPGNMAGNFNLSLQGCDQDAQSPGILRLQFQVLVQHPQNESNKIYVVDLSNERAMSLTIE 360
Seq70 --------KFVPGCFVCLESRTCSSNLTLTSGSKHKISFLCDDLTRLWMNVEKTISCTDH 52
Seq68 PRPVKQSR---------------------------------------------------- 339
Seq273 PRPVKQSRKFVPGCFVCLESRTCSSNLTLTSGSKHKISFLCDDLTRLWMNVEKTISCTDH 420
Seq70 RYCQRKSYSLQVPSDILHLPVELHDFSWKLLVPKDRLSLVLVPAQKLQQHTHEKPCNTSF 112
Seq68 ------------------------------------------------------------ 339
Seq273 RYCQRKSYSLQVPSDILHLPVELHDFSWKLLVPKDRLSLVLVPAQKLQQHTHEKPCNTSF 480
Seq70 SYLVASAIPSQDLYFGSFCPGGSIKQIQVKQNISVTLRTFAPSFQQEASRQGLTVSFIPY 172
Seq68 ------------------------------------------------------------ 339
Seq273 SYLVASAIPSQDLYFGSFCPGGSIKQIQVKQNISVTLRTFAPSFQQEASRQGLTVSFIPY 540
Seq70 FKEEGVFTVTPDTKSKVYLRTPNWDRGLPSLTSVSWNISVPRDQVACLTFFKERSGVVCQ 232
Seq68 ------------------------------------------------------------ 339
Seq273 FKEEGVFTVTPDTKSKVYLRTPNWDRGLPSLTSVSWNISVPRDQVACLTFFKERSGVVCQ 600
Seq70 TGRAFMIIQEQRTRAEEIFSLDEDVLPKPSFHHHSFWVNISNCSPTSGKQLDLLFSVTLT 292
Seq68 ------------------------------------------------------------ 339
Seq273 TGRAFMIIQEQRTRAEEIFSLDEDVLPKPSFHHHSFWVNISNCSPTSGKQLDLLFSVTLT 660
Seq70 PRTVDLTVILIAAVGGGVLLLSALGLIICCVKKKKKKTNKGPAVGIYNDNINTEMPRQPK 352
Seq68 ------------------------------------------------------------ 339
Seq273 PRTVDLTVILIAAVGGGVLLLSALGLIICCVKKKKKKTNKGPAVGIYNDNINTEMPRQPK 720
Seq70 KFQKGRKDNDSHVYAVIEDTMVYGHLLQDSSGSFLQPEVDTYRPFQGTMGVCPPSPPTIC 412
Seq68 ------------------------------------------------------------ 339
Seq273 KFQKGRKDNDSHVYAVIEDTMVYGHLLQDSSGSFLQPEVDTYRPFQGTMGVCPPSPPTIC 780
Seq70 SRAPTAKLATEEPPPRSPPESESEPYTFSHPNNGDVSSKDTDIPLLNTQEPMEPAE 468
Seq68 -------------------------------------------------------- 339
Seq273 SRAPTAKLATEEPPPRSPPESESEPYTFSHPNNGDVSSKDTDIPLLNTQEPMEPAE 836
Claim(s) 44, 52-53, recite(s) “a polynucleotide or set of polynucleotides encoding” in claim 44. The phrase “set of polynucleotides” is not defined in the instant disclosure. The broadest reasonable interpretation of “a polynucleotide or a set of polynucleotides encoding” is considered to be “one or more polynucleotides encoding”.
Claim Objections
Claim(s) 10 is objected to because of the following informalities: “271 (X9X10X12SX12YSHTWW VSYGX13)” in line 6 should be “271 (X9X10X11[[2]]SX12YSHTWWVSYGX13)”. Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of 35 U.S.C. 112(b):
(b) CONCLUSION.—The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the inventor or a joint inventor regards as the invention.
Claim(s) 1, 6, 19, 40 is/are rejected 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.
Claim(s) 1, 6, recite(s) “…does not bind to a full-length CDCP1 at a detectable level” in line(s) 4-5 of claim 1, rendering the claim(s) indefinite. The instant disclosure does not define ‘a detectable level’. Additionally, a skilled artisan would understand that limit of detection requires on a variety of factors including but not limited to (1) assay type (e.g., surface plasmon resonance, ELISA, flow cytometry, CyTOF, mass spectrometry, etc.), (2) reagents, (3) validation parameters, and (4) platform. Therefore, a skilled artisan would understand that an antibody with no detectable binding to full-length CDCP1 in one assay may exhibit detectable binding to full-length CDCP1 in another assay. Therefore, the limitation “at a detectable level” is considered indefinite. For the purposes of compact prosecution, the phrase will be considered to mean that the anti-cleaved human CDCP1 antibody preferentially binds (e.g., has a greater affinity for) cleaved CDCP1 than full-length CDCP1. This rejection may be overcome by amending claim(s) 1 to clearly recite the limitation(s) of the instant invention. Claim(s) 6, 12-17, 19, 40-41, 44, 52-53, 55, 60, 69 can overcome this rejection by amending claim(s) 1 as recited above.
Regarding claim(s) 19, the phrase "optionally" in line 8, rendering the claim indefinite because it is unclear whether the limitation(s) following the phrase are part of the claimed invention. See MPEP § 2173.05(h)(II). It is unclear if the limitation(s) following the phrase are required limitation(s). For the purposes of compact prosecution, the limitations following the phrase are not considered part of the claimed invention. This rejection may be overcome by amending claim(s) 19 to remove “optional” limitations and/or the phrase “optionally”.
Claim(s) 40 contain the trademark/trade name “DVD-Ig”. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify and/or describe a/an dual variable domain immunoglobulin (e.g., a type of bispecific antibody) and, accordingly, the identification/description is indefinite. This rejection can be overcome by amending claim(s) 40 to replace the term “DVD-Ig” with a generic phrase.
Claim Rejections - 35 USC § 112(a) – written description
Claim(s) 1, 6, 12-17, 19, 40-41, 44, 52-53, 55, 60, 69 is/are rejected 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. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention.
Claimed Invention
Claim(s) 1, 6, 12-17, 19, 40-41, 44, 52-53, 55, 60, 69, are drawn to an antibody or antigen binding fragment thereof that binds cleaved human CDCP1 antigen.
Breadth of Claims
The invention as disclosed in claim(s) 1 (and claim(s) 6) recite(s) “…antibody or antigen binding fragment thereof that specifically binds to…CDCP1…and…does not bind to a full-length human CDCP1 at a detectable level…”; claim(s) 12 (and claim(s) 13-17, 19, 40-41, 44, 52-53, 55, 60, 69) recite(s) “…wherein the VL-CDR3 comprises… SEQ ID NO: 3…”; claim(s) 13 recite(s) “…wherein the VL-CDR2 comprises… SEQ ID NO: 2…”; claim(s) 14 recite(s) “…wherein the VL-CDR1 comprises… SEQ ID NO: 1…”; claim(s) 15 recite(s) “…wherein the VH-CDR1 comprises… SEQ ID NO: 26…”; claim(s) 16 recite(s) “…wherein the VH-CDR2 comprises… SEQ ID NO: 30…”; claim(s) 17 recite(s) “…wherein the VH-CDR3 comprises… SEQ ID NO: 32…”. One of ordinary skill in the art would understand that the 6 CDRs of an antibody are responsible for antigen binding characteristics, including antigen specificity, and binding affinity. The claim does not disclose the structure (e.g., HCDR1-3 and LCDR1-3 sequences) associated with the claimed function(s). The instant disclosure does not provide a structure-function correlation that would allow for a person of ordinary skill in the art to envision light and heavy chain sequences, particularly in the CDR regions, such that the obtained structure would result in the claimed functions.
The invention as disclosed in claim(s) 19 is readable to 3CDRs, which is effectively half of an antibody binding site, as being sufficient for a functional antibody binding region. Specifically, the claim limitations as written require only the (I) VL (e.g., comprising LCDR1-3) or (II) VH (e.g., comprising HCDR1-3), which is half an antibody binding site missing either (I) VH complement (e.g., HCDR1-3), or (II) VL complement (e.g., LCDR1-3) that would create a full antibody binding site (e.g., 6 CDRs). One of ordinary skill in the art would understand that one cannot use half of an antibody binding domain (e.g., VL only, VH only) and reasonably expect to maintain cleaved human CDCP1 antigen binding function.
The invention as disclosed in claim(s) 19 recite(s) “…wherein the VH comprises at least about 70%...or at least about 99% sequence identity to…SEQ ID NO: 65…” and “…wherein the VL comprises at least about 70%...or at least about 99% sequence identity to…SEQ ID NO: 62…”. The claim(s) encompass a genus of heavy and/or light chain variable regions comprising variability (e.g., 70% identical) in both the heavy and/or light chain variable regions which are claimed as having the function of specifically binding to cleaved human CDCP1 antigen. This means that the variability in sequence identity can also occur in the CDRs, the domains that are critical for the antibody binding to its target, which one of ordinary skill in the art would understand to result in unpredictable binding characteristics with no reasonable expectation of maintaining cleaved human CDCP1 antigen binding. Additionally, the instant disclosure does not provide an adequate number of species of the claimed genus nor does the disclosure provide a structure-function correlation that would allow for a person of ordinary skill in the art to envision what variation can occur to the light and heavy chains, particularly in the CDR regions, such that the obtained structure would result in the claimed functions.
Scope of Disclosed Species
PNG
media_image1.png
200
400
media_image1.png
Greyscale
The anti-cleaved human CDCP1 antibodies of the elected species in the Applicant disclosure (see summary table above for details) with 100% sequence identity in the CDR regions of the heavy and light chain variable regions represents the anti-cleaved human CDCP1 antibodies of the elected species that the applicant was in possession of at the time of filing.
State of the Prior Art
At the time of filing, antibody functionality were known to depend on the entire structure, particularly a full complement of six CDRs. It is understood by one of ordinary skill in the art that that mutation to CDRs is unpredictable and that each construct requires function testing.
Sela-Culang, Kunik, and Ofran (Fron. Immuno., Vol. 4, Article 302, Oct. 2013), hereinafter “Sela-Culang”, reviews the structural basis of antibody-antigen recognition in the state of the art. Naturally occurring antibodies have six hypervariable loops are commonly termed complementary determining regions (CDRs) and are widely assumed to be responsible for antigen recognition [e.g., pg. 1, abstract; pg. 3, “The Role of CDRs and their Definition”]. A person of ordinary skill in the art would understand that although the above basics of antibody-antigen binding are known, that the specifics of antibody structure (e.g., within the CDRs) that underlie the antigen recognition are not well characterized [e.g., pg. 1, “The Motivations for…”].
Further, Herold et al. (Nature Scientific Reports, 7:12276, 25 Sep 2017), hereinafter “Herold”, teaches that it should be emphasized that there is no correlation between experimentally determined change in antibody binding affinity and a given mutation and additionally that no such correlation is expected because antigen binding is “affected by each CDR loop differently” and changes thereto “can in principle affect antigen binding affinity in an unpredictable way” [e.g., pg. 14, ¶ 2]. Further, Herold asserts that multiple determinants regulate antigen affinity and the interactions with CDRs are complex [e.g., pg. 14, ¶ 3].
At the time of filing, US 2020/0181281 A1 (hereinafter “US281”) taught anti-cleaved human CDCP1 that preferentially binds cleaved CDCP1 over full-length CDCP1 [e.g., ¶ 0784, 0818-0821; fig. 17]. US281 taught various separate species of anti-cleaved human CDCP1 antibodies [e.g., ¶ 0818-0821; fig. 17]. Therefore, the prior art demonstrates that the binding of cleaved human CDCP1 is possible by various anti-cleaved human CDCP1 antibodies. The prior art does not teach a known structure activity relationship for HCDR1-3 and LCDR1-3 in anti-cleaved human CDCP1 antibody that would allow prediction of CDR residues that specifically bind to cleaved human CDCP1 antigen.
Thus, an antibody’ six CDR’s specific antigen binding and affinity, and any alteration to CDR sequence(s) thereof, is a highly unpredictable process. One skilled in the art could not a priori make any predications regarding CDR sequences, or changes thereto, with any reasonable expectation of success nor envisage the breadth of structurally unrelated CDR combinations that would still possess the required function(s).
Conclusion
As indicated by the art, a full complement of 6 CDRs are required for antigen binding and one cannot predict which (I) HCDR1-3 and LCDR1-3 sequences would bind cleaved human CDCP1, or (II) CDR residue(s) may be changed and still result in an antibody that binds cleaved human CDCP1. Written description can be met if the claims recite the minimal structure that is needed to perform the function recited in the claims. Above, the art indicates that the 6 CDRs in an antibody antigen-binding domain are the minimal structure that binds to a target antigen. Specifically, Applicant claim(s) 1 and 19 would need to recite the 6 CDRs (e.g., LCDR1-3 and HCDR1-3 sequences) in the antibody that bind cleaved human CDCP1 antigen, without variability in the sequences thereof. Claim(s) 6, 12-17, 40-41, 44, 52-53, 55, 60, 69 can overcome this rejection by amending claim(s) 1 as recited above. It is noted for the record, that after amending claim 1 as recited above, either claim(s) 10 or claim(s) 12-18, depending on how Applicant decides to amend claim 1, would no longer be considered further limiting.
Claim Rejections - 35 USC § 112(a) – scope of enablement
Claim(s) 69 is/are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for a method of killing a tumor wherein the tumor cell has cleaved CDCP1 on the tumor cell surface, does not reasonably provide enablement for the treatment of all cancers (e.g., including those without the cleaved CDCP1 on the surface of the tumor cell). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation."' (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (A) The nature of the invention; (B) The breadth of the claims; (C) The amount of direction provided by the inventor; (D) The existence of working examples; (E) The state of the prior art; (F) The level of predictability in the art; (G) The quantity of experimentation needed to make or use the invention based on the content of the disclosure and (H) The level of one of ordinary skill. While all of these factors are considered, a sufficient amount for amount for a prima facie case are discussed below.
The nature of the invention
Claims 69 is/are drawn to a method killing a tumor cell comprising administering to the subject an anti-cleaved human CDCP1 antibody.
The breadth of the claims
The claim is broad in that it encompasses the killing of all tumor cells.
The instant specification discloses “…The present disclosure provides antibodies that specifically bind to a cleaved CDCP1 (e.g., human or mouse CDCP1), and antigen-binding fragments thereof, compositions comprising such antibodies, and methods of using such antibodies for preventing or treating diseases or conditions which comprise a tumor (e.g., cancers that have cleaved CDCP1 present on the cancer cell surface) in a subject.” [e.g., paragraph 0003].
The amount of direction provided by the inventor/the existence of working examples
The examples of the instant disclosed studies include: schematic of CDCP1 antibody, various analyses of CDCP1 antigen(s), protein fusions (e.g., Fc fusions), and antibody interactions [e.g., Figs. 1A-1K]; proteolytic studies [e.g., Figs. 2A-2F]; CDCP1 ectodomain engineering studies [e.g., Figs. 3A-3N]; HEK293T cells stably transduced with CDCP1 ectodomain strategy and studies [e.g., Figs. 4A-4I]; anti-cleaved CDP1 antibody generation and testing [e.g., Figs. 5A-5O]; NTF-Fc immobilization [e.g., Figs. 6A-6E]; BLI assays [e.g., Figs. 7A-7B]; mouse CDCP1 and tumor killing studies [e.g., Figs. 8A-8G]; mouse anti-cleaved CDCP1 antibody studies [e.g., Figs. 9A-9G, 11]; in vitro CL03 Fab studies [e.g., Fig. 10]; EM, Fourier shell studies [e.g., Figs. ]; CL03 binding ELISA [e.g., Fig. 13]; CL03 competition assay [e.g., Figs. 14A-14B]; graphical representations of tumor volume and weight [e.g., Figs. 15A-15B]; survival graph [e.g., Fig. 15C]; BLI assay results graph [e.g., Fig. 16A]; and SEC traces of antibodies [e.g., Fig. 16B].
The examples provided do not demonstrate the killing tumors with full-length human CDCP1. There is no rationale found in the prior art or the instant disclosure to suggest that an antibody that doesn’t bind to the
The state of the art/the level of predictability in the art
One of ordinary skill in the art would understand that there is no rationale, nor was any found during prior art searching, to suggest that an anti-cleaved human CDCP1 antibody would be enabled to kill tumor cells that do not express surface cleaved human CDCP1. In fact, a skilled artisan would expect an antibody to not mediate killing of cells it does not/cannot bind.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
Based on the instant disclosure and prior art, there is reason to expect an anti-cleaved human CDCP1 antibody to mediate killing of tumors without the target antigen on the surface. Therefore, in order to practice the invention as claimed, one of ordinary skill in the art would have to perform undue experimentation to determine if there are mechanisms by which an anti-cleaved human CDCP1 antibody could possibly mediate killing of tumor cells that do not express the target antigen on the tumor cell surface. Applicant is enabled for killing of tumor cells expressing surface cleaved human CDCP1.
Conclusion
In view of the Wands factors as discussed above, one of ordinary skill in the art would have to engage in undue experimentation to practice the full scope of the instant claimed invention. As such, instant claim(s) 69 was/were determined to not meet the scope of enablement requirement of 35 USC § 112(a).
Enablement can be met by amending claim(s) 69 to specify that the tumors express the cleaved human CDCP1 target antigen on the tumor cell surface.
Claim Rejections - 35 USC § 102
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action.
Claim(s) 1, 6 is/are rejected under 35 U.S.C. 102(a)(1) and 102(a)(2) as being anticipated by US 2020/0181281 A1 (hereinafter “US281”).
Regarding instant claim(s) 1, US281 teaches an anti-cleaved human CDCP1 antibody that preferentially binds cleaved CDCP1 (e.g., does not detectably bind full-length CDCP1; see 112b rejection for details) [e.g., ¶ 0784, 0818-0821; fig. 17].
Regarding instant claim(s) 6, US281 teaches the CDCP1 cleavage site is R368 (see claim interpretation above for details) [e.g., tbl. 5; fig. 1A].
Allowable Subject Matter
Claim(s) 10, 18, 23 is/are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Specifically, the anti-cleaved human CDCP1 antibody and/or antigen binding domain thereof comprising (1) HCDR1-3 of SEQ ID NOs: 26, 30, 32 and LCDR1-3 of SEQ ID NOs: 1-3 (e.g., claim 18); (2) a VH/VL of SEQ ID NOs: 65/62 (e.g., claim 23); or (3) HCDR1-3 of SEQ ID NOs: 269, 270, 271 and LCDR1-3 of SEQ ID NOs: 1, 2, 268 (e.g., claim 10), were found to be nonobvious in view of the closest prior art (see summary tables below for sequence details). Briefly, a sequence search of the prior art returned no 100% matches to any of the instant claimed HCDR1-3 sequence sets, and therefore cannot return any 100% matches to the instant claimed anti-cleaved human CDCP1 antibodies as indicated in the summary tables below (see closest prior art alignments below).
PNG
media_image1.png
200
400
media_image1.png
Greyscale
PNG
media_image2.png
200
400
media_image2.png
Greyscale
PNG
media_image3.png
200
400
media_image3.png
Greyscale
Alignment of anti-cleaved human CDCP1 “CL03 Fab” HCDR1-3 (SEQ ID NOs: 26, 30, 32) with WO2005012531-A2 (Clone YS6-NTV from library YS-A/B that binds target neutravidin protein):
PNG
media_image4.png
158
623
media_image4.png
Greyscale
Alignment of anti-cleaved human CDCP1 HCDR1-3 (SEQ ID NOs: 269-271) with WO2005012531-A2 (Clone YS6-NTV from library YS-A/B that binds target neutravidin protein):
PNG
media_image5.png
148
620
media_image5.png
Greyscale
Conclusion
No claims are currently allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to AMY M CHATTIN whose telephone number is (571)270-0646. The examiner can normally be reached T-F 0600-1600 PST.
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.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
/AMY M. CHATTIN/Examiner, Art Unit 1643
/GARY B NICKOL/Primary Examiner, Art Unit 1643
Prosecution Insights