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 .
DETAILED ACTION
Status of the Claims
1. Claims 1-16 are the original claims filed 3/22/2022. In the Preliminary Amendment of 3/22/2022, claims 3-5, 7-8, 10-13, and 16 are amended and new claim 17 is added. In the Reply of 6/4/2025, no amendments or changes are made to claims 1-17. Claims 1-17 are all the claims. In the Response of 10/7/2025, Claims 1-10, 12, and 14 are amended, claims 11 and 17 are cancelled, and new claims 18-27 are added.
Claims 1-10, 12-16, and 18-27 are all the claims.
The amendment of the claims raises new grounds for objection and rejection. The Office Action is final.
Priority
2. USAN 17/762,463, filed 03/22/2022, is a National Stage entry of PCT/EP2020/077008, International Filing Date: 09/25/2020, and claims foreign priority to EP 19199639.6, filed 09/25/2019.
Information Disclosure Statement
3. As of 11/24/2025, a total of one (1) IDS is filed: 3/22/2022. The corresponding initialed and dated 1449 form is considered and of record.
Withdrawal of Objections
Specification
4. The objection to the disclosure because of informalities is withdrawn.
a) The specification is amended to rectify the improper use of the term, i.e., ATCC, Nanobody, Tecan, Nano Drop, TSKgel, which is a trade name or a mark used in commerce.
b) The specification is amended to delete an embedded hyperlink and/or other form of browser-executable code: (http://www.ncbi.nlm.nih.gov/).
c) The specification is amended to include SEQ ID NOs for peptide sequences that are > 4 amino acids in length: (GGSGG)2,
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44
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.
d) The specification is amended in the figure legend to Figure 1 to identify the sequences depicted in the actual figure by sequence identifier.
Claim Objections
5. The objection to the Claims 1-17 because informalities is moot for the canceled claims and withdrawn for the pending claims.
a) Claims 1-17 are amended recite the full name for the EHD2 domain in the first instance for claim 1: “EH domain-containing protein 2” for the EHD2 domain.
b) Claim 3 is amended to recite “according to claim 1.”
c) Claim 10 is amended to replace “carries” with “comprises.”
d) Claim 14 is amended to recite “[of] according to claim 13”.
e) Claim 17 is canceled.
.
Withdrawal of Rejections
Claim Rejections - 35 USC § 112(b)
6. The rejection of Claims 4-5, 7-8, and 11-12 under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite is moot for canceled claim 11 and withdrawn for the pending claims.
-) Claims 4-5, 7-8, and
Claim Rejections - 35 USC § 112(a)
Enablement
7. The rejection of Claim 17 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the enablement requirement is moot for the canceled claim.
Claim Rejections - 35 USC § 103
8. The rejection of Claims 1-17 under 35 U.S.C. 103 as being obvious over Dong (PTO 892; 4/16/2025) in view of Blankenship (PTO 892; 4/16/2025) is moot for canceled claims 11 and 17 and withdrawn for the pending claims.
The instant claimed SEQ ID NO: 1 does not have sufficient correspondence at the recited amino acid residues for the instant claims to SEQ ID NO: 227 of Blankenship:
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542
1058
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no SEQ ID NO: 208 of Blankenship
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532
1030
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Rejections Withdrawn-in-Part/ Maintained-in-Part
Claim Rejections - 35 USC § 112(a)
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 the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Written Description
9. The rejection of Claims 25-27 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 moot for canceled claims 11 and 17, withdrawn-in-part, and maintained-in-part.
withdrawn-in-part
Claims 1-10, 12-16, and 18-24 are amended to identify the residue substitution for the Cys14 and Cys102 of SEQ ID NO: 1.
Insofar as the EHD2 substitutions associated with the antigen binding domain, Table 1 is accessible in its presentation for the substitutions in the Cys14 and Cys102 positions:
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1092
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Accordingly, it is clarified that at least for these examples, EHD2-1 and EHD2-2 are not modified so that the sequence “does not have a Cys at position 14” or “does not have a Cys at position 102” by way of a deletion. Instead, Table 1 also corresponds to the amino acid substitutions of claim 11 for the Cys14 and Cys102 residues, respectively. Furthermore, a review of Applicants rebuttal to the outstanding grounds for rejection under 35 USC 103 (see below) shows by their own admission of record that Ser14 and Ser102 are the preferred operative embodiments for the binding molecules of the invention.
maintained-in-part
New claims 25-27 are joined under the rejection for the same rationale used to reject canceled claim 17, namely, the specification does not support the use of the binding molecule recognizing any target antigen on a cancer to prevent the cancer.
“treatment/ treat”: the specification is unequivocal that treatment encompasses both prevention “and/or” treatment at [0132] The term “pharmaceutical composition” as used herein refers to a substance and/or a combination of substances being used for the identification, prevention or treatment of a disease or tissue status. The pharmaceutical composition is formulated to be suitable for administration to a patient in order to prevent and/or treat a disease.
The instant specification fails to describe a representative number of species to provide adequate written description of the claimed genus as per MPEP § 2163.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through establishment of a structure-function correlation (by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics) or through a sufficient description of a representative number of species. Either is considered sufficient to show the applicant was in possession of the claimed genus.
The POSA could reasonably conclude that any method claim(s) encompass prophylactic outcomes.
The rejection is maintained.
New Grounds for Objection
Claim Objections
10. Claims 1-10, 12-16, and 18-27 are objected to because of the following informalities:
a) Amend Claims 1-10, 12-16, and 18-27 for consistency to recite “selected from a VH and a VL.” Claim 1 recites “selected from VH and VL” whilst claims 4 and 7-8 recite “selected from a VH and a VL.”
b) Claims 4-9 and 18-20 are confusing and inconsistent with respect to claim construction compared to generic claim 1. Claim 1 is drawn to a (first) binding module consisting or elements a) and b) that are each set forth as a first and second polypeptide, respectively. Amending claims 4-9 and 18-20 to comport with respective modules comprising: elements a) and b) for a third (and fourth) polypeptide (claims 4-6 and 18-19); elements a) and b) for a fifth (and sixth) polypeptide (claim 7 and 20); and elements a) and b) for a seventh (and eighth) polypeptide (claims 8-9) could overcome this objection for lack of clarity and reduction in verbiage of the claims.
c) Claims 8-9 depend from claim 6. Claim 6 is drawn to a module comprising a third and fourth binding domain whilst claims 8-9 are drawn to a further binding module having seventh and eighth binding domains. The modules comprising the fifth and sixth binding domains are all together missing as between claims 6 and 8-9.
d) Claims 13-15 are drawn to “a nucleic acid” or “set of nucleic acids.” Amend the claims to replace a nucleic acid or a set of nucleic acids with one or more polynucleotides. A polynucleotide is the physical, long chain of nucleotides, while the sequence is the specific order of those nucleotides (bases) along the chain. A nucleic acid is the biological molecule itself (like DNA or RNA), which is a type of polynucleotide, and its identity is defined by its unique sequence.
e) New Claims 26-27 are objected to under 37 CFR 1.75 as being a substantial duplicate of new claim 25 much less in depending from claim 25. When two (or more) claims in an application are duplicates (or triplicates) or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 608.01(m). The claimed subject matter is not further limiting or differentiating between the three claims where claims 26-27 depend from claim 25.
f) Amend new claims 26-27 for clarity and to comport with new claim 25 to recite:
Claim 26 A method of treating cancer, comprising administering to a patient in need thereof , a therapeutically effective amount of the binding molecule according to claim 25, wherein the cancer is treated.
Claim 27 A method of treating cancer, comprising administering to a patient in need thereof , a therapeutically effective amount of the binding molecule according to claim 26, wherein the cancer is treated .
Appropriate correction is required.
New Grounds for Rejection
Claim Rejections - 35 USC § 112
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 the first paragraph of pre-AIA 35 U.S.C. 112:
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 of carrying out his invention.
Written Description
11. Claims 1-10, 12-16, 18-23 and 25-27 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.
Note: claim 24 is not included under this rejection because the construct binding molecules comprise from one to two VH/VL pair(s).
Claims 1, 4, and 7-8 specifically recite Markush groups drawn to a VH and a VL. A Markush group comprises a list of components (e.g., VH and VL), while only one member from that list needs to be part of any single embodiment of the claimed structure, not both simultaneously. The Markush group describes a list of mutually exclusive, alternatively usable members for a specific position in a chemical structure or process. See MPEP 2117.
Where a Markush grouping describes alternative chemical compounds, whether by words or chemical formulas, and the compounds do not appear to be members of a recognized physical or chemical class or members of an art-recognized class, the members are considered to share a “single structural similarity” and common use when the alternatively usable compounds share a substantial structural feature that is essential to a common use. Ex parte Hozumi, 3 USPQ2d 1059, 1060 (Bd. Pat. App. & Int. 1984). See also subsection II.B, below
While a VH and a VL share a common use in a conventional antibody binding domain, the single domain VH or VL structure is art-recognized having a structural distinction between the species. Here is the case where Applicants have not shown themselves to be in possession of a single domain antibody that possesses binding activity for just any antigen much less a cancer antigen that can be used in the treatment of just any cancer. For example, those data in Table 1 comprising the mutated EHD2-1 and EHD2-2 structures are shown for Fd/light chain combinations (VH and VL).
The instant specification fails to describe a representative number of species to provide adequate written description of the claimed genus as per MPEP § 2163.
MPEP § 2163 states that the written description requirement for a claimed genus may be satisfied through establishment of a structure-function correlation (by disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics) or through a sufficient description of a representative number of species. Either is considered sufficient to show the applicant was in possession of the claimed genus.
The POSA could reasonably conclude that the breadth and scope of the claimed subject matter is not met by the disclosure of the specification in order to satisfy the written description requirements.
Enablement
12. Claims 25-27 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 enablement requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to enable one skilled in the art to which it pertains, or with which it is most nearly connected, to make and/or use the invention.
Factors to be considered in determining whether undue experimentation is required, are summarized in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). They include the nature of the invention, the state of the prior art, the relative skill of those in the art, the amount of direction or guidance disclosed in the specification, the presence or absence of working examples, the predictability of the art, the breadth of the claims, the quantity of experimentation which would be required in order to practice the invention as claimed.
Claim interpretation
Claim 25 A method of treating cancer, comprising administering to a patient in need thereof, a therapeutically effective amount of the binding molecule according to claim 22, wherein the cancer is treated.
Claim 26 A method of treating cancer, comprising administering to a patient in need thereof a therapeutically effective amount to treat the cancer of the binding molecule according to claim 25.
Claim 27 A method of treating cancer, comprising administering to a patient in need thereof a therapeutically effective amount to treat the cancer of the binding molecule according to claim 26.
“treatment/ treat”: the specification is unequivocal that treatment encompasses both prevention at [0132] The term “pharmaceutical composition” as used herein refers to a substance and/or a combination of substances being used for the identification, prevention or treatment of a disease or tissue status. The pharmaceutical composition is formulated to be suitable for administration to a patient in order to prevent and/or treat a disease.
The POSA could reasonably conclude that the method claims 25-27 encompass prophylactic outcomes.
The Patent Act requires that patent applicant describes the invention in explicit terms to enable any person skilled in the art to make and use the invention. 35 U.S.C. 112. Applicants seek protection for over potentially millions of binding molecules that the specification does not teach or enable absent undue amounts of experimentation. The enablement requirement is a crucial aspect of the patent “bargain”: an inventor is granted limited protection from competition in exchange for publicly disclosing their new technology. See the decision in Morse, Incandescent Lamp, and Holland Furniture, establishing the requirement that if a patent claims an entire class or genus of processes, machines, or compositions of matter, the specification must enable a person skilled in the field to make and use the entire class. If a patent claims an entire class of processes, machines, manufactures, or compositions of matter, the patent’s specification must enable a person skilled in the art to make and use the entire class. In other words, the specification must enable the full scope of the invention as defined by its claims. The more one claims, the more one must enable. See §112(a); see also Continental Paper Bag Co. v. Eastern Paper Bag Co., 210 U. S. 405 (1908) (“[T]he claims measure the invention.”)
Disclosure in the Specification
The specification does not demonstrate a single much less a representative number of examples for the full breadth and scope of Claims 25-27 in preventing any cancer in a patient using a cancer cell line or by an, in vivo, animal model correlate for a cancer.
The scope of the claims must bear a reasonable correlation with the scope of enablement. See In re Fisher, 166 USPQ 19, 24 (CCPA 1970). "[T]o be enabling, the specification of a patent must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation.'" Genentech, Inc. v. Novo Nordisk, A/S, 108 F.3d 1361, 1365 (Fed. Cir. 1997) (quoting In re Wright, 999 F.2d 1557, 1561 (Fed. Cir. 1993)).
Conclusion
13. No claims are allowed.
14. The sequences in Claim 24 for SEQ ID NOs: 11-12, 14, 16, 20, 22, 31, 36-40, 42-44, 46-50 and 52-53 are free from the art.
15. For claim 24, the sequence of SEQ ID NO: 9 is identical to SEQ ID NO: 126 in USAN 19/477,748 (KUHL; Lennart);
the sequence of SEQ ID NO: 10 is identical to SEQ ID NO: 125 in USAN 19/477,748 (KUHL; Lennart);
the sequence of SEQ ID NO: 15 is identical to SEQ ID NO: 24 in USAN 19/477,748 (KUHL; Lennart);
the sequence of SEQ ID NO: 13 is identical to: SEQ ID NO: 30 in USAN 16/982,714 (US 20210002376); SEQ ID NO: 5 in 16/326,864 (US 20190194350); Sequence 11 in 17/762,626 (US 20220396635); Sequence 30 in 18/452,699 (US 20240059779);
the sequence of SEQ ID NO: 25 is identical to sequence 243 in 15/558,372 (US 10428149); sequence 18 in 16/982,714 (US 11780926); sequence 31 in 16/326,864 (US 11008402); sequence 244 in 15,558,372 (US 10428149); sequence 18 and 20 in 18/452,699 (US 20240059779);
the sequence of SEQ ID NO:45 is identical to sequence 37 in 17/762,626 (US 20220396635);
the sequence of SEQ ID NO: 51 is identical to sequence 205, 227, 218, in 17/185,340 (US 11168128); sequence 227 in 17/384,665 (US 11479599); sequence 31 in 17/226153 (US 11192904); sequence 205 in 17/384,665 (US 11479599); sequence 31 in 17/405,246 (US 11220536); sequence 31 in 17/405,650 (US 11414479); sequence 126 in 17/501,955 (US 11440952).
16. 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.
17. Any inquiry concerning this communication or earlier communications from the examiner should be directed to LYNN A. BRISTOL whose telephone number is (571)272-6883. The examiner can normally be reached Mon-Fri 9 AM-5 PM.
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, Wu Julie 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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LYNN ANNE BRISTOL
Primary Examiner
Art Unit 1643
/LYNN A BRISTOL/Primary Examiner, Art Unit 1643