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 .
Applicant’s amendment and remarks filed on 12/17/2025 are acknowledged. Claims 6, 8, 16, 20, 24, 27, and 30 are amended. Claims 1-32 are pending.
Election/Restrictions
Applicant's election with traverse of Group I, OR2H1, antibody fragments with the Vh and VL sequences of 40 and 44 and CDR sequences of SEQ ID NO:41-47 in the reply filed on 12/17/2025 is acknowledged. The traversal is on the following ground(s):
1. That the examiner has not shown that it would be a serious burden to search and examine Groups I and II together.
2. That this application is a National Stage application and thus, unity of invention rules apply to the restriction. Applicant argues that claims to the different categories of invention recited in 37 CFR 1.475(b) “will be considered to have unity of invention if the claims are drawn only to one of the following combinations.” Applicant argues that Groups I and II fall under (b)(2).
3. That the number of species recited in the claims is a finite number of species and is not unreasonable, therefore, there would not be a burden to search all of the species.
This is not found persuasive for the following reasons.
Regarding argument 1, this application was filed as a National Stage application. Therefore, rules regarding unity of invention apply to restriction and burden is not relevant.
Regarding argument 2, first, in any combination of categories, the different inventions must share a special technical feature for there to be unity of invention. As set forth in the restriction requirement, the groups do not share a special technical feature. Second, as applicant pointed out, the different categories of invention recited in 37 CFR 1.475(b) “will be considered to have unity of invention if the claims are drawn only to one of the following combinations.” The instant claims do not fit any of the stated categories.
Regarding argument 3, first, as stated above, burden is not relevant to unity of invention. Second, applicant is vastly understating the search burden for the sequences recited in the claims. Each sequence requires searches in multiple databases. Even limiting the search to the elected species requires 72 separate searches. In addition, with the possible combinations of species recited, there are not only 45 separate species, there are hundreds of thousands of possible species.
The requirement is still deemed proper and is therefore made FINAL.
Claims 3-4, 7-18, and 23-32 are withdrawn from further consideration pursuant to 37 CFR 1.142(b), as being drawn to a nonelected invention or species, there being no allowable generic or linking claim. Claims 1-2, 5-6, and 19-22 are currently under examination.
Information Disclosure Statement
The information disclosure statement filed on 5/3/2024 has been considered. A signed copy is enclosed.
Drawings
The drawings are objected to because Figures 1-7B contain text and pictures that are not clearly legible. Corrected drawing sheets in compliance with 37 CFR 1.121(d) are required in reply to the Office action to avoid abandonment of the application. Any amended replacement drawing sheet should include all of the figures appearing on the immediate prior version of the sheet, even if only one figure is being amended. The figure or figure number of an amended drawing should not be labeled as “amended.” If a drawing figure is to be canceled, the appropriate figure must be removed from the replacement sheet, and where necessary, the remaining figures must be renumbered and appropriate changes made to the brief description of the several views of the drawings for consistency. Additional replacement sheets may be necessary to show the renumbering of the remaining figures. Each drawing sheet submitted after the filing date of an application must be labeled in the top margin as either “Replacement Sheet” or “New Sheet” pursuant to 37 CFR 1.121(d). If the changes are not accepted by the examiner, the applicant will be notified and informed of any required corrective action in the next Office action. The objection to the drawings will not be held in abeyance.
Specification
This application fails to comply with the requirements of 37 C.F.R. 1.821-1.825 because it contains nucleotide sequences that are not identified on pages 54-59 and 62-63. Appropriate sequence identifiers should be used to comply with sequence rules. The sequences in the specification should match the sequence listing and computer readable form (CRF) submitted with the application. Applicant is asked to review the specification for sequences that are not identified and correction is required. Applicant must provide a substitute computer readable form (CRF) copy of the “Sequence Listing”, a substitute paper copy of the “Sequence Listing”, an amendment of the specification to insert appropriate sequence identifiers, and a statement that the content of the paper and computer readable copies are the same and, where applicable, include no new matter, as required by 37 C.F.R. 1.821(e) or 1.821(f) or 1.821(g) or 1.825(b) or 1.825(d).
The use of the multiple trademarks, including TWEEN, AKYNZEO, ABRAXANE, and many others, which are trade names or marks used in commerce, have been noted in this application (particularly on pages 26-29 and 48-52). The terms 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.
It is noted that the cited occurrences of improper use are only exemplary and applicant should review the specification to correct any other use of trademarks.
Claim Rejections - 35 USC § 112
The following is a quotation 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 (pre-AIA ), first paragraph:
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, 5-6, and 19-22 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The instant claims are drawn to antigen binding molecules that bind to one of 13 olfactory receptors. The antigen binding molecules include RNAi, peptide, protein, chimeric antigen receptor (CAR) T cell, CAR NK cell, CAR macrophage (CARMA), siRNA, immunotoxin, diabody, antibody, and functional antibody fragments. Dependent claims recite specific CDR and V heavy and V light chain sequences.
The specification does not disclose any RNAi, CAR NK cell, CAR macrophage (CARMA), siRNA, immunotoxin, or diabodies that bind to any of the recited olfactory receptors. Likewise, no binding molecules are disclosed for any receptors other than OR5V1 and OR2H1. For OR5V1, only the sequences for a CAR and CAR T cell are disclosed. For OR2H1, the sequences for a CAR and CAR T cell are disclosed as well as the CDR and V heavy and V light chain sequences of two ScFv fragments are disclosed. The claims encompass a set of disparate molecules that bind antigens but are related only in their function. Peptides do not bind to an antigen the way siRNA would. Immunotoxins do not bind the same way a general peptide would. Antibodies do not bind the same way that RNA does. Where specific sequences are recited, it is noted that the full antibody is not required. The claims that recite Vh and Vl chains only require one of the chains. Where CDRs are recited, only one CDR is required.
The claims require binding to specific olfactory receptors, but only require one of the listed CDRs. However, the specification does not describe any antibodies that do not have six specific CDRs and the full length Vh and Vl chains.
The functional characteristics of antibodies (including binding specificity and affinity are dictated by their structure. Amino acid sequence and conformation of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. For example, Vajdos et al. (J Mol Biol. 2002 Jul 5;320(2):415-28 at 416) teaches that, “ … Even within the Fv, antigen binding is primarily mediated by the complementarity determining regions (CDRs), six hypervariable loops (three each in the heavy and light chains) which together present a large contiguous surface for potential antigen binding. Aside from the CDRs, the Fv also contains more highly conserved framework segments which connect the CDRs and are mainly involved in supporting the CDR loop conformations, although in some cases, framework residues also contact antigen. As an important step to understanding how a particular antibody functions, it would be very useful to assess the contributions of each CDR side-chain to antigen binding, and in so doing, to produce a functional map of the antigen-binding site." The art shows an unpredictable effect when making single versus multiple changes to any given CDR. For example, Brown et al. (J Immunol. 1996 May;156(9):3285-91 at 3290 and Tables 1 and 2), describes how the VH CDR2 of a particular antibody was generally tolerant of single amino acid changes, however the antibody lost binding upon introduction of two amino changes in the same region.
Recently, the U.S. Court of Appeals for the Federal Circuit (Federal Circuit) decided Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017), which concerned adequate written description for claims drawn to antibodies. The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. § 112(a) requires adequate written description of the antibody itself. Amgen, 872 F.3d at 1378-79. The Amgen court expressly stated that the so-called "newly characterized antigen" test, which had been based on an example in USPTO-issued training materials and was noted in dicta in several earlier Federal Circuit decisions, should not be used in determining whether there is adequate written description under 35 U.S.C. § 112(a) for a claim drawn to an antibody. Citing its decision in Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., the court also stressed that the "newly characterized antigen" test could not stand because it contradicted the quid pro quo of the patent system whereby one must describe an invention in order to obtain a patent. Amgen, 872 F.3d at 1378-79, quoting Ariad Pharmaceuticals, Inc. v. Eli Lilly & Co., 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone should not be considered adequate written description of a claimed antibody to that newly characterized antigen, even when preparation of such an antibody is routine and conventional. Other than the CARs and two antibodies with the disclosed CDRs described in the specification, applicant has not described any antibodies that have the required function and have provided no description or guidance as to what structural features will provide the required function.
The specification discloses only four species within the vast instant claims scope and does not provide any guidance as to which amino acids can be varied (even while keeping a single CDR, as required) while retaining the appropriate binding activity.
Therefore, neither the art nor the specification provide a sufficient representative number of antibodies or a sufficient structure-function correlation to meet the written description requirements.
Claim Rejections - 35 USC § 102
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.
Claims 1-2 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Flegel et al (Frontiers in Mol. Biosciences, 2:1-14, 2016; IDS filed 5/3/2024).
The instant claims are drawn to antigen binding molecules that selectively bind to an olfactory receptor.
Flegel et al disclose antibodies that bind to OR2H1 (see column 1, page 3).
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brian J Gangle whose telephone number is (571)272-1181. The examiner can normally be reached M-F, 9-6:30.
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, Daniel Kolker can be reached at 571-272-3181. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRIAN GANGLE/ Primary Examiner, Art Unit 1645
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