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 .
Election/Restrictions
1. Applicant’s election without traverse of Group VIII, directed to the anti-C5 antibodies ATG-008 and ATG-012, and encompassing claim 12 in full and each of claims 1, 4, 13, 62-70, 72, 77 and 79 in part, in the reply filed on November 4, 2025 is acknowledged.
2. However, upon further consideration and review of the disclosure, the restriction among the different antibodies (Groups I-VIII) set forth in the restriction requirement mailed 06/04/2025 is hereby withdrawn and all antibody groups will be examined together.
3. Claims 1, 4-13, 62-70, 72, 77 and 79 are under examination in the current office action.
Information Disclosure Statement
4. The information disclosure statements (IDSs) filed 07/27/2021, 07/19/2022 and 11/04/2025 have been considered and the references therein are of record.
Specification
5. The disclosure is objected to because of the following informalities:
The use of the term “nanobody”, which is a trade name or a mark used in commerce, has been noted in this application. See p. 84 line 27 in the specification as originally filed. 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. Pendency
Appropriate correction is required.
Claim Objections
6. Claims 1 and 62 are objected to because of the following informalities:
In claim 1, there appears to be a typographical mistake at line 2, which recites “…component 5 (CS),…” instead of C5 (i.e., the “S” should be a “5”).
In claim 62, the use of numbering lists or items within a claim (i.e., “(1)”, “(2)”) is discouraged because of the similarity with, and therefore potential misperception with, claim numbering. It is therefore suggested that the listed items be amended to recite (a) and (b), or else (i) and (ii).
Appropriate correction is required.
Claim Rejections - 35 USC § 112
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.
7. Claim 62 is 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 62 recites an antibody molecule that comprises “at least one of the paratope-paratope contacts described in Table 6”. However, MPEP 2173.05(s) states that: “[w]here possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table ‘is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim. Incorporation by reference is a necessity doctrine, not for applicant’s convenience.’” Ex parte Fressola, 27 USPQ2d 1608, 1609 (Bd. Pat. App. & Inter. 1993).
Claims should not refer back to tables in the specification. Applicants are advised to copy the table contents into the claim itself.
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.
8. Claims 62-64 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.
Claim 62 is drawn to an antibody molecule capable of binding to C5, comprising LCDR1, LCDR2, LCDR3, HCDR1 and HCDR2 belonging to Chothia CDR canonical classes 2, 1, 1, 1 and 2, respectively; and the antibody comprises at least one of the paratope-paratope contacts described in Table 6. Claim 63 recites an antibody molecule that binds competes for binding to CD5 with an antibody molecule of claim 1. And claim 64 recites an antibody molecule that binds to the same or overlapping epitope as the epitope recognized by the antibody of claim 1. Hence, the claims are directed to a genus of antibodies claimed entirely by function (i.e., antigen reactivity) but with little or no defined structure.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
The factors to be considered when analyzing claims for compliance with the written description requirement include: actual reduction to practice; disclosure of drawings or structural chemical formulas; sufficient relevant identifying characteristics (e.g., disclosure of complete or partial structure, physical and/or chemical properties, structure/function correlation); method of making the claimed invention; level of skill and knowledge in the art; and predictability in the art. See MPEP §2163.
With respect to antibodies, the Federal Circuit has clarified Written Description as it applies to antibodies in the recent decision Amgen v. Sanofi, 872 F.3d 1367 (Fed. Cir. 2017). The Federal Circuit explained in Amgen that when an antibody is claimed, 35 U.S.C. 112(a) (or pre-AIA first paragraph) 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, 598 F.3d 1336, 1345 (Fed. Cir. 2010). In view of the Amgen decision, adequate written description of a newly characterized antigen alone is not considered adequate written description of a claimed antibody to that antigen, even when preparation of such an antibody is routine and conventional. Id.
The recitation of an antibody that competes for binding to an antigen against a different antibody, or that binds the same epitope as a different antibody, represent functional characteristics with no structure. The recitation of an antibody capable of binding to C5 whose CDRs belong to certain Chothia CDR canonical classes, and that comprises at least one paratope-paratope contact according to Table 6 represents a functional characteristic with broadly defined structure. While generically the structure of antibodies is known, the structure of the presently claimed antibodies can vary substantially within the above given claimed recitations. Thus, the genus is highly variant because a significant number of structural differences between genus members is permitted.
The instant specification teaches the production of several monoclonal antibodies (mAbs) that bind complement C5 protein (ATG-001, ATG-002, ATG-003, ATG-004, ATG-005, ATG-006, ATG-007, ATG-008, ATG-012 and ATG-013). The heavy chain and light chain CDRs for these mAbs share a high degree of similarity and/or are identical (see Tables 3 and 4), because each of the CDRs can be represented by a consensus sequence (as recited in present claim 1). The specification also describes eight pairs of exemplary paratope-paratope contacts in the anti-C5 antibodies (Table 6 at p. 155). Note also that only one of the paratope-paratope contacts is required by claim 62. However, the specification’s limited disclosure does not provide sufficient structural description, nor structure-function correlation, for the vast genus of anti-C5 antibodies encompassed by the claims.
Accordingly, the instant application is lacking sufficient guidance on the structural attributes of an antibody that correlates to the functional requirements of the claimed invention. Regardless, the relevant art recognizes that diversity of antibodies binding to any particular target antigen or epitope is extremely broad, and therefore there is no way to reasonably predict the structure of the antigen-binding region of an antibody based upon the structure of an antigen or epitope alone (see, for example, Lloyd et al. Protein Eng. Design & Select, 2009, 22(3):159-168; and Edwards et al. J. Mol. Biol. 2003, 334:103-118). Consequently, in the absence of sufficient recitation of distinguishing identifying characteristics, the specification does not provide adequate written description of the claimed genus nor guidance as to which of the myriad of molecules encompassed by the claimed antibodies would meet the limitations of the claims.
The limited examples of related monoclonal antibodies directed against the C5 antigen therefore does not represent the astronomical and potentially unknowable breadth of all possible amino acid sequences which will result in the desired binding or functional properties of the claimed antibodies. This is exemplified by the Court decision in Abbvie (Abbvie v Janssen, 759 F.3d 1285 (Fed. Cir. 2014)), where Abbvie developed over 200 antibodies that shared 99.5% identity in the variable regions and which bound the target, but in no way allowed one to envisage the unique structure of a competitor’s (Centocor) antibodies which bound the same target but shared only 50% sequence similarity. Additionally, as noted in Amgen, knowledge that an antibody binds to a particular epitope on an antigen tells one nothing at all about the structure of the antibody, wherein “instead of analogizing the antibody-antigen relationship to a ‘key in a lock,’ it [is] more apt to analogize it to a lock and ‘a ring with a million keys on it.” (Internal citations omitted, emphasis in original). Therefore, those of skill in the art would not accept a disclosure of the several, highly similar anti-C5 monoclonal antibodies as evidence that the inventor had been in possession of the genus of functionally-recited antibodies presently claimed.
Functionally defined genus claims can be inherently vulnerable to invalidity challenge for lack of written description support, especially in technology fields that are highly unpredictable, where it is difficult to establish a correlation between structure and function for the whole genus or to predict what would be covered by the functionally claimed genus. Abbvie Deutschland GMBH & Co. v. Janssen Biotech, Inc. (Fed. Cir. 2014, Appeal No. 13-1338 at page 26).
9. Claims 72 and 77 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 treating or reducing the risk of developing a Complement component (C5)-associated disorder in a subject comprising administering an anti-C5 antibody of the invention, does not reasonably provide enablement for a method of treating or preventing any disorder as broadly claimed. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to practice the invention commensurate in scope with these claims.
The factors to be considered in determining whether a disclosure would require undue experimentation include (1) the quantity of experimentation necessary, (2) the amount of direction or guidance presented, (3) the presence or absence of working examples, (4) the nature of the invention, (5) the state of the prior art, (6) the relative skill of those in the art, (7) the predictability or unpredictability of the art and, (8) the breadth of the claims. In re Wands, 8 USPQ2d, 1400 (CAFC 1988).
The claims are broadly drawn to a method of treating a disorder, or a method of preventing a disorder, wherein each method comprises administering to a subject in need thereof an antibody molecule of claim 1, in an amount effective to treat the disorder. Thus, the claims broadly encompass the treatment or prevention of any disorder comprising administering an antibody capable of binding to complement component 5 (C5).
However, the instant specification teaches that the disclosed antibodies are useful for treating a complement-associated disorder, such as at p. 73, lines 12-24. These disorders are stated to include “ischemia-reperfusion injury, atypical hemolytic uremic syndrome (aHUS), typical or infectious hemolytic uremic syndrome (tHUS), dense deposit disease (DDD), paroxysmal nocturnal hemoglobinuria (PNH), neuromyelitis optica (NMO), macular degeneration, thrombotic thrombocytopenic purpura (TTP), myasthenia gravis, cold agglutinin disease, Guillain-Barre Syndrome, Degos’ disease, graft rejection, sepsis, glomerulonephritis, and thrombotic microangiopathy (TMA).” Indeed, the specification at p. 80 defines the term “treat” as “e.g., a complement-associated disorder, means that a subject (e.g., a human) who has a disorder, e.g., a complement-associated disorder, and/or experiences a symptom of a disorder, e.g., a complement-associated disorder, will, in an embodiment, suffer less a sever symptom and/or recover faster when an antibody molecule is administered than if the antibody molecule were never administered.” Similarly, the term “prevent” is defined in terms of a complement-associated disorder, and that a subject is less likely to have a complement-associated disorder if the subject receives the antibody molecule. Thus, the specification’s guidance is limited to treating or preventing complement-associated disorders.
The prior art also recognizes that antibodies directed against complement C5, such as the antibody known as eculizumab, are effective for the treatment of complement-associated disorders, such as PNH or aHUS (see Wong et al. Translational Res. 2015, 165(2):306-320). However, neither the instant application nor the prior art provides evidence that the anti-C5 antibodies of the invention could reasonably be used in the treatment or prevention of non-complement-associated disorders. For example, there is no evidence of record to indicate that any of the disclosed anti-C5 antibodies would be therapeutically beneficial for the treatment of, for example, amyotrophic lateral sclerosis (ALS), diabetes (type 1 or 2), cystic fibrosis, or any other disorder that does not stem from or primarily affect the complement system. For that matter, there is no evidence to suggest that the claimed antibodies would be at all effective or beneficial in disorders not directly associated with or driven by C5 complement activation. Undue experimentation would thus be required to determine with disorders could reasonably be treated or prevented in a subject by administering an anti-C5 antibody of the invention.
The test of enablement is not whether any experimentation is necessary, but whether, if experimentation is necessary, it is undue. In view of the breadth of the claims, the lack of guidance and working examples provided in the specification, the high level of unpredictability as evidenced by the prior art, and the amount of required experimentation, it is the examiner’s position that undue experimentation would be necessary for a skilled artisan to make and use the entire scope of the claimed invention. Applicants have not provided sufficient guidance to enable one of ordinary skill in the art to practice the claimed invention in a manner reasonably correlated with the scope of the claims. The scope of the claims must bear a reasonable correlation with the scope of enablement (In re Fisher, 166 USPQ 19 24 (CCPA 1970)). Without sufficient guidance, determination of having the desired biological characteristics is unpredictable and the experimentation left to those skilled in the art is unnecessarily, and improperly, extensive and undue. See In re Wands 858 F.2d 731, 8 USPQ2nd 1400 (Fed. Cir., 1988).
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.
10. Claim(s) 63-64 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Wong et al. (Translational Res. 2015, 165(2):306-320).
Claim Interpretation
Claim 63 is directed to an antibody molecule that competes for binding to C5 with an antibody molecule of claim 1, and claim 64 recites an antibody molecule that binds to the same or overlapping epitope recognized by an antibody molecule of claim 1. The instant specification does not specifically identify the epitope(s) on or within C5 that an antibody of claim 1 binds, but instead states at p. 155 (lines 20-22) that: “[t]he antibody molecule described herein can bind to an epitope on C5 (e.g., human C5). For example, an epitope bound by an antibody molecule described herein can include one or more epitope contact points in a C5 protein sequence described herein.” Given this broad definition for epitope, therefore, the broadest reasonable interpretation (BRI) applied to present claims 63-64 is an antibody that binds to C5.
Wong et al. teach a humanized monoclonal antibody (called eculizumab) that is directed against human C5 protein (see abstract and “Eculizumab” at p. 307). Eculizumab thus binds to an epitope on human C5 protein, and therefore meets the BRI of instant claims 63-64.
Conclusion
11. Claims 62-64, 72 and 77 are rejected.
Claim 1 is objected to for minor informalities.
Claims 1, 4-13, 65-70 and 79 are directed to allowable subject matter. The prior art does not teach or reasonably suggest an anti-C5 antibody according to the presently recited claims. In particular, the CDR sequences of at least SEQ ID NOs: 22, 35, 38, 48, 49, 60, 66, 71 and 82 are novel and are not taught or suggested as prior art antibody CDRs.
Advisory Information
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Kimberly A. Ballard whose telephone number is (571)272-2150. The examiner can normally be reached Mon-Fri 8AM - 5PM EST.
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, Jeffrey Stucker can be reached at 571-272-0911. 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.
/KIMBERLY BALLARD/Primary Examiner, Art Unit 1675