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 .
Continued Examination Under 37 CFR 1.114
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and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114.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 01/14/2026 has been entered.
Claim Status
Claims 2-3, 5-9, 11-21, 27-30, 32-35, 37, 40-42, 48-50, 52, and 52-62 have been cancelled; claim 51 has been amended; and, claim 63 has been newly added, as requested in the amendment filed on 01/14/2026. Following the amendment, claims 1, 4, 10, 22-26, 31, 36, 38-39, 43-47, 51, 53, and 63 are pending in the instant application.
Claims 1, 4, 10, 22-26, 31, 36, 38-39, 43-47, 51, 53, and 63 are under examination in the instant office action.
Priority - Updated
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged.
Claims 1, 4, 10, 22-26, 31, 36, 38-39, 43-47, 51, 53, and 63 have an effective filing date of February 20, 2020 corresponding to PRO 62/978,915.
Drawings - Objection Withdrawn
Applicant has submitted a replacement drawing sheet for Figure 1, wherein all text/labels are legible. As such, the objection to the drawings is withdrawn.
Claim Rejections - 35 USC § 112 - Withdrawn
Claims 1, 4-5, 10, 22-26, 31, 36, 38-39, 43-47, 51, and 53 were rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, regarding scope of enablement. On Pages 11-15 of Remarks (01/14/2026), Applicant argues that a person having ordinary skill in the art would understand how to make and use the claimed monoclonal antibody without undue experimentation; one having ordinary skill in the art would (i) understand that CDRs as defined by Kabat has weaknesses and may not accurately identify true CDRs responsible for antigen binding; (ii) would have been aware of several other CDR standardization approaches (e.g., Chothia, Marin (AbM), Gelfand, Contact, Wolfguy, Honneger, IMGT, etc.); and (iii) would have been aware of antibody annotation tools using integrated antibody sequence and/or structural data to provide accurate CDR information. With regard to claim 51 specifically, Applicant argues that the claim has been amended to require that the cells of the cancer express endoglin. With regard to new claim 63, Applicant argues that the claim requires the CDRs of the monoclonal antibody validated by Applicant and thus is also enabled.
Applicant’s arguments and/or amendments above are deemed persuasive. As such, the rejection of claims 1, 4-5, 10, 22-26, 31, 36, 38-39, 43-47, 51, and 53 under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, regarding scope of enablement is withdrawn.
Allowable Subject Matter
As previously indicated, an endoglin antibody or fragment thereof, including a nucleic acid sequence encoding said antibody or fragment thereof, comprising all six of the CDRs recited in claims 1 and 36 have been thoroughly searched and are free of the prior art. Additionally, with regard to claim 10, an scFv comprising the nucleic acid sequences corresponding to one of SEQ ID NOs: 13-16 and an scFv comprising both SEQ ID NOs: 17 and 18 have been thoroughly searched and are free of the prior art. It is specifically noted that the only 100% matches to SEQ ID NO: 17 are the instant application and the related WO 2021/167952 A2 document. 100% matches were found for SEQ ID NO: 18, however the 100% matches for SEQ ID NO: 18 were related to antibodies that bind antigens that are not endoglin. As such, claims 1, 4, 10, 22, 23, 31, 38-39, 43, 46-47, and 63 are allowed.
Claim Rejections - 35 USC § 112 - New
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.
Claim 36 is 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. This is a WRITTEN DESCRIPTION rejection.
The claim is drawn to an isolated nucleic acid encoding (i) a heavy chain variable region of an antibody which comprises instant SEQ ID NOs: 3, 4, and 5 wherein a complex forms between the heavy chain variable region and its complementary light chain variable region, the complex binds endoglin; and/or (ii) a light chain variable region of an antibody which comprises instant SEQ ID NOs: 6, 7, and 8 wherein a complex forms between the light chain variable region and its complementary heavy chain variable region, the complex binds endoglin.
Thus, the claims identify (i) a heavy chain variable region defined by partial sequence structure that comprises SEQ ID NOs: 3, 4, and 5, which may form an endoglin-binding complex with a complimentary light chain variable region and/or (ii) a light chain variable region defined by partial sequence structure that comprises SEQ ID NOs: 6, 7, and 8, which may form an endoglin-binding complex with a complimentary heavy chain variable region. Thus, the claims encompass a vast genus of isolated nucleic acid sequences encoding heavy chain variable and/or light chain variable regions, each of which may form endoglin-binding complexes with complementary light/heavy chain variable regions, respectively.
The instant specification discloses an endoglin-binding (i.e., agonist) IgM monoclonal antibody designated as “A18-384” or “A18”, wherein said antibody comprises heavy chain CDRs 1-3 corresponding to instant SEQ ID NOs: 3-5, respectively, and light chain CDRs 1-3 corresponding to instant SEQ ID NOs: 6-8, respectively (see Page 42). The specification further discloses the generation of recombinant antibodies (i.e., scFvs), wherein it is noted that the recombinant antibodies comprise heavy chain CDRs 1-3 corresponding to instant SEQ ID NOs: 3-5, respectively, and light chain CDRs 1-3 corresponding to instant SEQ ID NOs: 6-8 (see Page 43).
Thus, the instant specification discloses making four structurally similar endoglin-binding antibodies and describes the complete heavy chain CDRs 1-3 corresponding to instant SEQ ID NOs: 3-5, respectively, and light chain CDRs 1-3 corresponding to instant SEQ ID NOs: 6-8, respectively, which together endow the ability to bind endoglin; i.e., heavy chain variable domains comprising SEQ ID NOs: 3-5 and light chain variable domains comprising SEQ ID NOs: 6-8 are complementary . The specification fails to disclose any other complementary sequences that complex and subsequently possess the function of binding to endoglin.
To provide adequate written description and evidence of possession of the claimed antibody genus, the instant specification can structurally describe alternative representative antibodies/complexes that function to bind endoglin, or describe structural features common to the members of the genus, which features constitute a substantial portion of the genus. Alternatively, the specification can show that the claimed invention is complete by disclosure of sufficiently detailed, relevant identifying characteristics, functional characteristics when coupled with a known or disclosed correlation between function and structure, or some combination of such characteristics (see University of California v. Eli Lilly and Co., 119 F.3d 1559, 43 USPQ2d 1398 (Fed. Cir. 1997) and Enzo Biochem, Inc. V. Gen-Probe Inc.).
In this case, the only factor present in the claims is a recitation of the complex function, “bind endoglin”, and partial sequence structures as stated above. The instant specification fails to describe structural features common to the members of the antibody genus, which features constitute a substantial portion of the genus because the instant specification fails to disclose additional complementary variable domains that complex and function to bind endoglin. A definition by function does not suffice to define the genus because it is only an indication of what the antibody does, rather than what it is. Other than for the antibodies disclosed at Pages 42-43, the specification fails to provide the heavy chain variable region and/or light chain variable region structural features coupled to the claimed functional characteristics. The instant specification fails to describe a representative number of additional complementary variable domains that complex and function to bind endoglin for the genus of nucleic acids/antibodies that function as claimed. Accordingly, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus required to make the claimed antibodies.
Although Applicants may argue that it is possible to screen for complementary variable domains that complex (i.e., antibodies) and function to bind endoglin as claimed, the court found in (Rochester v. Searle, 358 F.3d 916, Fed Cir., 2004) that screening assays are not sufficient to provide adequate written description for an invention because they are merely a wish or plan for obtaining the claimed chemical invention. “As we held in Lilly, “[a]n adequate written description of a DNA … ‘requires a precise definition, such as by structure, formula, chemical name, or physical properties,’ not a mere wish or plan for obtaining the claimed chemical invention.” 119 F.3d at 1566 (quoting Fiers, 984 F.2d at 1171). For reasons stated above, that requirement applies just as well to non-DNA (or RNA) chemical inventions.” Knowledge of screening methods provides no information about the structure of any future antibodies yet to be discovered that may function as claimed. The endoglin antigen provides no information about the structure of an antibody that binds to it.
Given the lack of representative examples to support the full scope of the claimed nucleic acids/antibodies/complexes, the present claim lacks adequate written description. Thus, the specification does not provide an adequate written description of nucleic acids that are complementary and complex to bind endoglin, that are required to practice the claimed 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.
The following is a quotation of 35 U.S.C. 112 (pre-AIA ), second paragraph:
The specification shall conclude with one or more claims particularly pointing out and distinctly claiming the subject matter which the applicant regards as his invention.
Claims 24-26, 44-45, 51, and 53 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.
With regard to claims 24-26, the claims recite “[t]he agonist anti-ENG coreceptor antibody of claim 1”, “[t]he anti-ENG coreceptor-binding agonist antibody fragment of claim 1”, and “[t]he agonist anti-ENG coreceptor antibody of claim 1, which is IgM”, respectively (emphasis added). The recitation of an “agonist” antibody/antibody fragment in claims 24-26 render the claims indefinite as there is no reference to an agonist antibody in independent claim 1, and as such the agonist antibodies as recited in claims 24-26 lack proper antecedent basis.
With regard to claims 44-45 and 51, the claims recite “or a composition comprising such”; it is unclear as to what “such” encompasses. Therefore, claims 44-45 and 51 are considered to be indefinite. Claim 53 is also included in this rejection as it depends from claim 51.
Claim Rejections - 35 USC § 102 - New
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.
Claim 36 is rejected under 35 U.S.C. 102(a)(1) and (a)(2) as being anticipated by WO 1995/027045 A1 (herein after referred to as "Smith").
With regard to claim 36, Smith is drawn to methods for producing catalytic antibodies, including human catalytic antibodies, from bacteriophage. Specifically, it is noted that Figure 9 of Smith shows the genetic sequence of light chain pattern A and light chain pattern C from mouse-derived RT3 phage antibodies, including the nucleic acid sequence and corresponding amino acid sequence; the sequence of Smith Figure 9 comprises 100% matches to instant SEQ ID NOs: 6, 7, and 8, respectively. Figure 9 shows eight different light chains used with the 15 different clones from pattern A; the chain associated with clones mR6 and mR8, differs from the
germline V gene by a single silent nucleotide change, the chain used in mR9, mRl8 and
mR27 differs from mR6 and mR8 by an additional single silent mutation, and therefore these 5 clones share the same protein sequence as the germline (Page 41). Thus, Smith discloses antibody light chains, and their respective nucleic acid sequences, wherein said light chains comprise exact matches to instant SEQ ID NOs: 6, 7, and 8. Furthermore, it is noted that the wherein clause of claim 36 states the intended result of complex formation between the light chain variable region and its complementary heavy chain variable region, the complex being capable of binding endoglin. The wherein clause, however, does not require complex formation between the light chain variable domain and a complementary heavy chain and does not limit the claim to a particular structure/antigen binding functionality, and therefore is not given weight (see MPEP 2111.04).
Thus, the amino acid sequence, and corresponding nucleic acid sequence, disclosed by Figure 9 of Smith anticipates the isolated nucleic acid sequence encoding a light chain variable region of an antibody which comprises instant SEQ ID NOs: 6, 7, and 8.
Conclusion
Claims 1, 4, 10, 22-26, 31, 36, 38-39, 43-47, 51, 53, and 63 are pending. Claims 24-26, 36, 44-45, 51, and 53 are rejected. Claims 1, 4, 10, 22, 23, 31, 38-39, 43, 46-47, and 63 are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to ALYSSA RAE STONEBRAKER whose telephone number is (571)270-0863. The examiner can normally be reached Monday-Thursday 7:00 am - 5:00 pm.
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/ALYSSA RAE STONEBRAKER/Examiner, Art Unit 1642
/Laura B Goddard/Primary Examiner, Art Unit 1642