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 .
Priority
The instant application is claiming the benefit as a 35 U.S.C. 371 national phase application from, and claims priority to, International Application No. PCT/US2022/074276, filing date 07/28/2022, which claims the benefit of the prior-filed United States Provisional Patent Application No. 63/228,005, filing date 07/30/2021.
Status of Application/Claims
The preliminary amendment, filed 02/27/2025, is acknowledged. Claims 3-28, 30-55, 64, 72, and 76-83 are canceled. Claims 2, 63, and 65 are currently amended. Claims 1-2, 29, 56-63, 65-71, 73-75, and 84 are currently pending and are examined on the merits herein.
Information Disclosure Statements
The information disclosure statements (IDSs) submitted on 02/27/2025 and 11/19/2025 have been fully considered by the examiner.
Specification
The use of the terms Sigma Aldrich, Peprotech, BioRad, Thermo Fisher Scientific, Life Technologies, Lonza, Santa Cruz, Cell Signaling, R&D Systems, Proteintech, Invitrogen, Addgene, Molecule Devices, Envigo, Caliper, Corning, ClonaCell, Essen BioScience, Pierce, and Vector Labs, which are trade names or marks used in commerce, have been noted in this application. The terms should be in all caps wherever they appear or, where appropriate, include a proper symbol indicating use in commerce such as ™, SM , or ® following the terms.
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.
Claim Objections
Claims 66-67, 71, 73-75, and 84 are objected to because of the following informalities:
Claims 66-67, 71, 73-74 recite “an antibody” which should be corrected to “the antibody” to clarify proper antecedent basis.
Claim 73 additionally recites “A method of manufacturing an antibody comprising…” in line 1, which should be corrected to “A method of manufacturing the antibody of claim 1 comprising…”.
Claim 75 recites the limitation “skin cancer” twice, in lines 2 and 4. One of these terms should be deleted.
Claim 84 recites “The methods…” which should be corrected to “The method…”.
Appropriate correction is required.
Claim Rejections - 35 USC § 112(b)
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 1-2, 29, 56, 60, and 84 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.
Claims 1-2 and 56 are indefinite because the B18 antibody, or an antibody comprising all six CDRs from B18, is recited as specifically binding OSMR; whereas the specification states that B18 does not specifically bind OSMR (p.67, [00236]).
Claim 29 recites the limitation "the humanized VH domain" in lines 3 and 4 (two instances). There is insufficient antecedent basis for this limitation in the claim. Additionally, the use of the term “humanized” in each of (i) through (xxvi) in claim 29 is indefinite because applicant disclosure supports that the antibodies are of human origin (p.53, [00192]). Thus, it is unclear how one would humanize a human antibody.
Claim 60 is also rejected for indefiniteness due to the use of the terms “human” and “humanized” because applicant disclosure supports that the antibodies are of human origin (p.53, [00192]). Thus, it is unclear how one would humanize a human antibody.
Claim 84 recites the limitation "the chemotherapy" in line 1. There is insufficient antecedent basis for this limitation in the claim.
Additionally, claim 84 recites dependency on claim 83 which has been canceled; thus, the claim is rendered indefinite.
Additionally, claim 84 contains the trademark/trade names Taxol®, Taxotere®, Alymsys®, Avastin®, Mvasi®, Zirabev®, Zejula®, Rubraca® and Lynparza®. 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/describe chemotherapies and ply ADP ribose polymerase (PARP) inhibitors, and, accordingly, the identification/description is indefinite.
Additionally, claim 84 recites “…(or cisplatin)…(Taxol®)… (Taxotere®)…(Alymsys®, Avastin®, Mvasi®, Zirabev®)… (such as but not limited to, niraparib (Zejula®) rucaparib (Rubraca®) and olaparib (Lynparza®)…” It is unclear whether the terms in parentheses are to be considered as merely examples or a required scope limitations. Further, the phrase "such as" renders the claim indefinite because it is unclear whether the limitations following the phrase are part of the claimed invention. See MPEP § 2173.05(d).
For purposes of further examination, the scope is interpreted to be any chemotherapy that is carboplatin, taxane, docetaxel, bevacizumab; or, any poly ADP ribose polymerase (PARP) inhibitor; or any combination thereof.
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.
Claims 1-2, 29, 57-63, 65-67, 71, 73-75, and 84 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. THIS IS A WRITTEN DESCRIPTION REJECTION.
Regarding instant claim 1, the claim is inclusive of a genus of antibodies that specifically bind to OSMR and competes for binding with B01, B02, B03, B04, B05, B06, B07, B08, B09, B010, B12, B13, B14, B16, B17, B18, B19, B21, H09, H10, H11, H12, H13, H14, H15, and H16. The disclosure defines structures for 26 antibodies which were assessed for OSMR binding. The disclosure explicitly states that B18 antibody did not show any specific binding to OSMR (p.67, [00236]. Thus, specification discloses amino acid sequence structures for 25 antibodies that were found to exhibit binding activity toward OSMR: B01, B02, B03, B04, B05, B06, B07, B08, B09, B010, B12, B13, B14, B16, B17, B18, B19, B21, H09, H10, H11, H12, H13, H14, H15, and H16 (p.54, [00194]. There is otherwise no support in the disclosure for structures for antibodies that “compete for binding” with the aforementioned antibodies. Thus, the specification does not disclose, and the art does not teach, structures for the genus of antibodies with the claimed function as broadly encompassed in the claim. Claims 57-63, 65-67, and 71 are dependent on claim 1 and do not overcome the issue, and are thus also rejected. Further, claim 65 also only requires 80% identity to the antibody of claim 1 and allows for variability in the CDR regions.
Regarding claims 2 and 29: Claim 2 is inclusive of a genus of antibodies wherein the recited VH and VL CDRs for B01, B02, B03, B04, B05, B06, B07, B08, B09, B010, B12, B13, B14, B16, B17, B18, B19, B21, H09, H10, H11, H12, H13, H14, H15, and H16 are interchangeable. Claim 29 is inclusive of a genus of antibodies wherein only 80% identity in the VH and VL domains is required and variability can occur within the CDR regions. As stated above, the disclosure only provides structures for 26 antibodies with defined combinations of CDRs, wherein only 25 antibodies with a defined combination of CDRs were found to bind OSMR (p.67, [00236]. There is no other data provided to support that any of the remaining various combinations of CDRs bind OSMR.
Regarding claim 73: Claim 73 is drawn to a method of manufacturing the antibody of claim 1 by expressing one or more polynucleotides encoding the antibody of claim 1. While the disclosure provides structures for the aforementioned 25 antibodies that bind OSMR, the disclosure does not reasonably provide structures for antibodies that “compete for binding” with these antibodies so that one skilled in the art could manufacture such an antibody.
Regarding claims 74-75 and 84: Claim 74 is drawn to a method of treating cancer by administering any of antibodies B01, B02, B03, B04, B05, B06, B07, B08, B09, B010, B12, B13, B14, B16, B17, B18, B19, B21, H09, H10, H11, H12, H13, H14, H15, and H16, or any antibody that competes with these antibodies for OSMR binding. The disclosure only sets forth 2 examples of antibodies which were shown to both bind OSMR and to treat cancer : namely, B14 which is encoded by a VH of SEQ ID NO: 37 (CDR1), SEQ ID NO: 38 (CDR2), and SEQ ID NO: 39 (CDR3) and a VL of SEQ ID NO: 103 (CDR1), tripeptide ‘AAS,’ and SEQ ID NO: 104); and B21 which is encoded by a VH of SEQ ID NO: 64 (CDR1), SEQ ID NO: 53 (CDR2), and SEQ ID NO: 54 and a VL of SEQ ID NO: 113, tripeptide ‘AAS,’ and SEQ ID NO: 114). Thus, the specification does not disclose, and the art does not teach, a genus of OSMR antibodies that treat cancer as is broadly encompassed in the claims. Claims 75 and 84 are dependent upon claim 74 and do not resolve the issue.
In regards to claims to a product defined by function, without a correlation between structure and function, the claims do little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement.
The state of the prior art is such that it is well established in the art that the formation of an intact antigen-binding site of antibodies generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs or hypervariable regions, which provide the majority of the contact residues for the binding of the antibody to its target epitope (see Paul. Fundamental Immunology, 3rd Edition, 1993, pp. 292-295; herein referred to as Paul). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity, which is characteristic of the immunoglobulin. It is expected that all of the heavy and light chain CDRs in their proper order and in the context of framework sequences which maintain their required conformation, are required in order to produce a protein having antigen-binding function and that proper association of heavy and light chain variable regions is required in order to form functional antigen binding sites (p.293, col.1-2, lines 3-8, line 31, and lines 27-30).
The instant specification fails to provide sufficient descriptive information, such as definitive structural features that are common to the genus. That is, the specification provides neither a representative number of antibodies that encompass the genus of antibodies with the claimed function nor does it provide a description of structural features that are common to the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus. Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
The “claims merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any compound later actually invented and determined to fall within the claim’s functional boundaries— leaving it to the pharmaceutical industry to complete an unfinished invention.” Ariad Pharmaceuticals, Inc. v. EliLilly and Co.,598 F.3d 1336, 1353 (Fed. Cir. 2010).
Because the disclosure fails to describe common attributes or characteristics that adequately identify members of the genus, and because the genus is highly variant, the disclosure of antibodies B01, B02, B03, B04, B05, B06, B07, B08, B09, B010, B12, B13, B14, B16, B17, B19, B21, H09, H10, H11, H12, H13, H14, H15, and H16 is insufficient to describe the genus. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
Claim Rejections - 35 USC § 103
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 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.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
Claim 69 is rejected under 35 U.S.C. 103 as being unpatentable over Walker, L.— US20200239550A1 (publication date: 7/30/2020; effective filing date: 10/13/2017; herein referred to as Walker).
[AltContent: textbox (Walker SEQ ID NO: 324 vs. Instant B01 CDRs 1-3 (underlined)[img-media_image1.png])]Walker teaches antibodies and antigen-binding polypeptides, and heavy and light chain sequences thereof. Walker teaches “Ab162,” which is encoded by variable light (VL) chain amino acid sequence SEQ ID NO: 324 which harbors instant CDR1-3 sequences for B01 (i.e., instant SEQ ID NO: 79-SSNIGAGYD, tripeptide GNS, and SEQ ID NO: 80-QSYDSSLSGWV, respectively; see below figure and Walker p.85, CDRs in boxes).
Walker does not explicitly teach that Ab162 is expressed via a polypeptide that is recombinantly produced (instant claim 69).
However, Walker also teaches that antibodies of the invention may be recombinant human antibodies (i.e., produced from recombinant polypeptides).
It would have been prima facie obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to combine the teachings of Walker by using a recombinant polypeptide to produce the VL chain comprising instant CDRs 1-3 of SEQ ID NO: 79, tripeptide GNS, and SEQ ID NO: 80, respectively, in order to arrive at the instantly claimed invention, because the combination of prior art elements according to known methods results in a predictable result of using a recombinant polypeptide to produce the VL antibody chain. One of ordinary skill in the art would have a reasonable expectation of success because Walker teaches a VL sequence that harbors all three CDRs.
Allowable Subject Matter
Claims 68 and 70 are allowed.
The following is an examiner’s statement of reasons for allowance: The closest prior art for a recombinant polypeptide encoding CDRs 1-3 is provided by Walker, which provides VL CDRs1-3 for B01 but not the VH CDRs1-3,as described in the prior art rejection above.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee. Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Jami M Gurley whose telephone number is (571)272-0117. The examiner can normally be reached Monday - Friday, 8am - 4pm.
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, Joanne Hama can be reached at 571-272-2911. 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.
/JAMI MICHELLE GURLEY/Examiner, Art Unit 1647
/JOANNE HAMA/Supervisory Patent Examiner, Art Unit 1647
Prosecution Insights