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 .
Claim Status
Applicant’s amendments and remarks, filed 06/10/2026, are acknowledged.
Claims 1-24, 28-30, and 43 are canceled.
Claims 26, 31, and 40-42 are amended.
Claim 48 is new.
Claims 25-27, 31-42, and 44-48 are pending.
As such, claims 25-27, 31-42, and 44-48 are pending examination and currently under consideration for patentability under 37 CFR 1.104.
DETAILED ACTION
Information Disclosure Statement
The information disclosure statement (IDS) submitted on 06/10/2026 is acknowledged. The submission is in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statement is being considered by the examiner.
Withdrawn Objections
The specification objections are withdrawn. Issues regarding minor informalities and trademarks/names have been sufficiently addressed through amendments to the specification on 06/10/2026.
The claim objections are withdrawn. Issues regarding minor informalities have been sufficiently addressed through amendments to the claims filed on 06/10/2026.
Withdrawn Rejections
Applicant’s arguments, see pages 8-11, filed 06/10/2026, with respect to:
Claims 25, 26, and 47;
Claim 26; and,
Claim 31
rejected under 35 USC 112(b) as allegedly being indefinite have been fully considered and are persuasive. The issue regarding the claims comprising indefinite language have been sufficiently addressed through amendments to the claims. As such, the rejection under 35 USC 112(b) is withdrawn.
Applicant’s arguments, see pages 11 and 12, filed 06/10/2026, with respect to claim 43 rejected under 35 USC 112(a) as allegedly lacking written description have been fully considered and are persuasive. The issue regarding the specification failing to disclose Applicant’s possession of the broad genus of bispecific or multispecific antibodies has been sufficiently addressed through amendments to the claims. Specifically, Examiner acknowledges that claim 43 is canceled thus rendering the rejection moot. As such, the rejection under 35 USC 112(a) is withdrawn.
The rejection of claims 25-27 and 31-47 under 35 USC 112(a) as allegedly failing to comply with the enablement requirement is modified in favor of Applicant’s arguments filed 06/10/2026. Specifically, Examiner acknowledges that the in vitro models disclosed in Example 2 provide sufficient correlation for claim 27 and its dependent claims. Applicant’s arguments, see pages 12-15, filed 06/10/2026, with respect to claims 25-27 and 31-47 rejected under 35 USC 112(a) have been fully considered.
Maintained Rejections
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 40-42 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 40-42 recite the limitation “are numbered according to the Kabat definition system”. This limitation incorporates a reference in the claim. MPEP2173.05(s) states:
Where possible, claims are to be complete in themselves. Incorporation by reference “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).
As such, claims 40-42 are rejected.
Applicant’s Arguments
Application respectfully requests withdrawal of the 112(b) rejection (see page 11 of the Remarks filed 6/10/2026). Applicant argues that the Kabat definition system is a widely adopted standard for consistently numbering the residues in an antibody… Therefore, to avoid the unnecessary duplication of tables and/or sequences defining a well- known numbering scheme, the claims as amended herein recite: "are numbered according to the Kabat definition system." A skilled person reading the present claims in light of the specification and having knowledge in the pertinent art would readily understand the meaning of the recited "Kabat definition system" and how to use this system based on the well-known numbering scheme to identify the appropriate residues. Thus, per MPEP § 2173.02(II), the claims are not indefinite.
Response to Arguments
Applicant's arguments filed 06/10/2026 have been fully considered but they are not persuasive. Examiner acknowledges the amendments to the claims; however, the amendments do not overcome the rejection as the language still incorporates a reference (i.e., Kabat definition system) into the claim. As stated in the MPEP and supported by Applicant’s remarks, the claims are interpreted in light of the specification. Because the specification indicates that the sequences are numbered according to the Kabat definition (see Tables 2-4 and Table 6), the claims are complete without the incorporation of reference language.
As such, the 112(b) rejection is maintained.
Claim Rejections - 35 USC § 112(a) Enablement
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 25, 26, 32-42, and 48 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.
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.
MPEP § 2164.01 states:
The standard for determining whether the specification meets the enablement
requirement was cast in the Supreme Court decision of Minerals Separation Ltd. v. Hyde, 242 U.S.
261, 270 (1916) which postured the question: is the experimentation needed to practice the
invention undue or unreasonable? That standard is still the one to be applied. In re Wands, 858
F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). Accordingly, even though the statute does
not use the term "undue experimentation," it has been interpreted to require that the claimed
invention be enabled so that any person skilled in the art can make and use the invention without
undue experimentation. In re Wands, 858 F.2d at 737, 8 USPQ2d at 1404 (Fed. Cir. 1988).
There are many factors to be considered when determining whether there is sufficient evidence
to support a determination that a disclosure does not satisfy the enablement requirement and whether
any necessary experimentation is "undue." These factors include, but are not limited to:
(A) The breadth of the claims;
(B) The nature of the invention;
(C) The state of the prior art;
(D) The level of one of ordinary skill;
(E) The level of predictability in the art;
(F) The amount of direction provided by the inventor;
(G) The existence of working examples; and
(H) The quantity of experimentation needed to make or use the invention based on the content
of the disclosure.
In re Wands, 858 F.2d 731, 737, 8 USPQ2d 1400, 1404 (Fed. Cir. 1988). The factors most relevant for this rejection are: (A) the breadth of the claims; (B) the nature of the invention; (E) the level of predictability in the art; (F) the amount of direction provided by the inventor; (G) the existence of working examples; and (H) the quantity of experimentation needed to make or use the invention based on the content of the disclosure.
In regard to Wands factors (A) and (B), the breadth of the claims needed to enable the invention
is determined by whether the scope of enablement provided to one skilled in the art by the disclosure is
commensurate with the scope of protection sought in the claims. AK Steel Corp. v. Sollac, 344 F.3d 1234, 1244, 68 USPQ2d 1280, 1287 (Fed. Cir. 2003); In re Moore, 439 F.2d 1232, 1236, 169 USPQ 236, 239 (CCPA 1971). The propriety of a rejection based upon the scope of a claim relative to the scope of the enablement concerns (1) how broad the claim is with respect to the disclosure and (2) whether one
skilled in the art could make and use the entire scope of the claimed invention without undue
experimentation.
The nature of the invention is a method of treating a subject having a complement-mediated disease or disorder, wherein the method comprises administering to the subject a therapeutically effective amount of a humanized antibody that binds specifically to human complement factor Bb protein, wherein the antibody comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 19 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 27. Therefore, the nature of the invention is a biochemical case, where there is natural unpredictability in performance of certain species other than those specifically enumerated; see MPEP § 2163. Accordingly, it is the Office’s position that undue experimentation would be required to practice the functionality of the claimed method, with a reasonable expectation of success, because it would not be predictable from the disclosure of any one particular species may or may not work; see MPEP § 2164.03.
In regard to Wands factors (C), (D), and (E), the state of the prior art is what one skilled in the art would have known, at the time the application was filed, about the subject matter to which the claimed invention pertains and provides evidence for the degree of predictability in the art; see MPEP § 2164.05(a). The claims encompass treating any complement-mediated disease or disorder with a humanized antibody that binds specifically to human complement factor Bb protein.
The art confirms the intricate complexity of the complement system. Morgan et al (Nat Rev Drug Discov 14, 857–877 (2015); previously submitted with the Office action mailed 03/10/2026) indicates that there will be a no ‘one size fits all’ solution to complement therapies because agents that are effective in one disease might do nothing in, or even exacerbate, another due to the inevitability that a drug that blocks any of the complement pathways will increase the risk of infections (see pg. 859, left col; pg. 861, left col). The merits of anti-complement therapy in preclinical models of disease have been explored in hundreds of papers; however, only a few drugs have entered clinical trials and fewer still have progressed beyond Phase I (see pg. 859, left col). Any drug that stops activation of the classical pathway will affect the clearance of immune complexes and apoptotic cells; and, inhibition of the activation pathways may disrupt an individual’s capacity to mount an adaptive immune response (see pg. 861, left col). Specifically, when activation fragments such as C3a, C5a, C4d, Bb and terminal complement complex (TCC) are present in the disease their levels can be monitored to demonstrate response to therapy and confirm target engagement; however, for diseases restricted to specific sites, for example, the retina, central nervous system or kidney glomerulus, plasma complement biomarkers may not reflect the response to therapy and are poor tools for assessing target engagement (see pg. 874). This is supported by Nilsson et al (Front. Immunol. 14:1334050 (2023) ; previously submitted with the Office action mailed 03/10/2026) who discuss the challenges encountered when accurately determining the complement status, particularly within the constraints of routine clinical practice including: pathway complexity, heterogeneity of complement-mediated diseases, patient heterogeneity, lack of sensitivity, sample sensitivity, and lack of standardization (see entire document). Specifically, Nilsson et al discuss that patients with complement disorders exhibit substantial clinical diversity and variations in complement profiles, and complement activation is highly dynamic and can change rapidly in response to stimuli (see pg. 2, left col).
With respect to the autoimmune diseases, an autoimmune disease is a condition arising from an abnormal immune response to a normal body part. Nearly any body part can be involved. Common symptoms include low grade fever and feeling tired. The cause is generally unknown. Examples include, multiple sclerosis, rheumatoid arthritis, and lupus.
Blumberg et al. (Nat Med. (2012); 18(1): 35–41; previously submitted with the Office action mailed 03/10/2026) teach that one of the greatest problems in translating therapies into clinical practice in autoimmunity are the numerous failures that have been the results of clinical trials. Despite the rapid progress that has been made in understanding the immune system, most of the underlying data has come from animal models, which necessarily only partially represent what is observed in humans. To compound this limitation, there exists no standardized definition of the normal human immune system, no comprehensive understanding of how this normal system is altered in autoimmune diseases and no understanding of the relationship between these immunophenotypic characteristics and either the genetic composition of the host or the environmental stimuli that either promote or protect from the development of autoimmunity (see pages 1-3). It is important to remember that the claims are even broader than the field of autoimmune disorders, including diseases such as, for example, fetal loss, ischemia/reperfusion injury and traumatic brain injury which are beyond the scope of autoimmune disorders.
As such, the art indicates complement diseases can affect the efficacy of therapeutics used to treat it. Therefore, the art is unpredictable regarding treatment of all complement diseases with a single compound or class of compounds.
In regard to Wands factors (F), (G) and (H), the amount of guidance or direction needed to enable the invention is inversely related to the amount of knowledge in the state of the art as well as the predictability in the art. In re Fisher, 427 F.2d 833, 839, 166 USPQ 18, 24 (CCPA 1970). The “amount of guidance or direction” refers to that information in the application, as originally filed, that teaches exactly how to make or use the invention. The more that is known in the prior art about the nature of the invention, how to make, and how to use the invention, and the more predictable the art is, the less information needs to be explicitly stated in the specification. In contrast, if little is known in the prior art about the nature of the invention and the art is unpredictable, the specification would need more detail as to how to make and use the invention in order to be enabling. See, e.g., Chiron Corp. v. Genentech
Inc., 363 F.3d 1247, 1254, 70 USPQ2d 1321, 1326 (Fed. Cir. 2004).
The claims are drawn to a method of treating a subject having a complement-mediated disease or disorder, wherein the method comprises administering to the subject a therapeutically effective amount of a humanized antibody that binds specifically to human complement factor Bb protein, wherein the antibody comprises a heavy chain variable region (VH) comprising the amino acid sequence of SEQ ID NO: 19 and a light chain variable region (VL) comprising the amino acid sequence of SEQ ID NO: 27.
The working examples provided by Applicant do not demonstrate a method of treating any complement-mediated disease or disorder in a subject comprising administering a humanized antibody that binds specifically to human complement factor Bb protein. Applicant has tested the kinetic parameters of several humanized variants and reference antibodies binding to Factor Bb (see Examples 1 and 2; Tables 7-11). Additionally, the Applicant has tested the inhibition activity of AP-mediated MAC deposition and AP-mediated hemolysis by the humanized variants (see Example 2; Tables 12 and 13). However, the working examples do not support that the claimed antibody would treat the vast genus of complement-mediated diseases or disorders. Because the specification only studied in vitro models of two complement pathway activities, one cannot assume that the method of treating a vast variety of disorders or diseases will work similarly to the in vitro models provided in the specification. In the absence of empirical determination, one skilled in the art would be subjected to undue experimentation to determine if the claimed method of treating any complement-mediated disease or disorder would result in therapeutic response as recited in the claims.
Applicant is reminded that “a patent is not a hunting license. It is not a reward for search, but compensation for its successful conclusion” and “[p]atent protection is granted in return for an enabling disclosure of an invention, not for vague intimations of general ideas that may or may not be workable”. See Genentech, 108 F.3d 1361, 1366 (Fed. Cir. 1997).
In view of all of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention, and thus, the claimed invention does not satisfy the requirements of 35 U.S.C. 112 first paragraph.
Applicant’s Arguments
Applicant respectfully disagrees and submits that the rejection fails to support a prima facie case of lack of enablement (see pages 12-15 of the Remarks filed on 06/10/2026).
The cited teachings in these references relate to challenges associated with clinical trials and individual patient response, but these teachings are not relevant to a proper enablement analysis of the present claims. The present claims do not expressly require clinical efficacy, and the USPTO and the courts have made clear that in such circumstances, considerations relating to clinical efficacy are not relevant to an enablement determination… The rejection seeks to apply a heightened standard based on the level of predictability of clinical efficacy and FDA approval, but this is not the standard by which enablement is evaluated. Thus, the conclusions with respect to Wands factors (C), (D), and (E) fail to support a prima facie case of lack of enablement because they are based on considerations that the USPTO and the courts have distinguished from findings that should be made for a proper enablement analysis… The present application includes experimental results relating to the humanization and evaluation of anti-factor Bb antibodies, including an antibody as recited in the present claims. The results in Example 2 demonstrate that the recited antibody inhibits membrane attack complex (MAC) deposition and alternative pathway (AP)-mediated hemolysis… Throughout the Specification and Examples, there is description of the mechanisms by which an effective amount of the recited anti-factor Bb antibody can elicit a therapeutic response (see, e.g. Specification [0232]-[0249], and Example 2). These mechanisms highlight certain qualities associated with effective treatment of complement-mediated disorders as recited in the claims. Moreover, these descriptions of activity and common knowledge in the art would allow for a skilled person to readily evaluate complement-mediated disease states for which treatment with the claimed anti-factor Bb antibody would be appropriate… Thus, even according to the art identified by the Examiner, methods for evaluating complement therapy in preclinical models of disease have been described in "hundreds of papers" that "date back more than 50 years," and proof-of-principal for therapeutic response is "readily obtained." The art therefore typically engages in any experimentation that may be required by a skilled person, and such experimentation would not be undue. Therefore, no undue experimentation is required in order to carry out the methods of the present claims, which are properly and sufficiently enabled by the present disclosure.
Response to Arguments
Applicant's arguments filed 06/10/2026 have been fully considered but they are not persuasive. Examiner respectfully disagrees with Applicant’s assertion that the rejection seeks to apply a heightened standard based on the level of predictability of clinical efficacy and FDA approval. Page 60 of the specification states that the term “treating” or “treatment” refers to at least an amelioration of the symptoms associated with pathological condition afflicting a subject, where amelioration is used in a broad sense to refer to at least a reduction in the magnitude of a parameter, e.g., symptom, associated with the pathological condition being treated, such as a complement-mediated disease or disorder. As such, treatment also includes situations where the pathological condition, or at least symptoms and/or secondary effects associated therewith, are completely inhibited, e.g., prevented from happening, or stopped, e.g., terminated, such that subject no longer suffers from the pathological condition, or at least the symptoms that characterize the pathological condition. Based on this definition, the working examples do not provide sufficient support or correlation that the claimed antibody is enabled for the method of treating claims (i.e., claims 25, 26, 32-42, and 48). Further, the examples provided in the specification are demonstrated via in vitro models. The MPEP is clear that an in vitro model example in the specification constitutes as a “working example” if that example correlates with a disclosed or claimed method invention (see MPEP 2164.02(II)). While the in vitro examples in the present specification may correlate to inhibiting MAC deposition and AP-mediated hemolysis, these examples do not correlate to treating a subject having a complement-mediated disease/disorder. Furthermore, due to the novelty of the antibody and consequently the lack of prior art regarding said antibody, it’s claimed functions within a subject would be unpredictable without undue experimentation.
As such, the enablement rejection is maintained.
Allowable Subject Matter
Claims 27, 31, and 44-47 are allowed. SEQ ID Nos: 19 and 27 appear to be free of the art. The closest prior art is Panicker et al (US 2019/0153079 A1; publication date: 05/23/2019) which teach of anti-complement factor Bb antibodies and methods of using said antibodies (see Abstract). The antibodies of Panicker et al are structurally different from the claimed antibody of the present invention (see alignment below). Additionally, as stated above, the present specification provides in vitro examples in the present specification which correlate to inhibiting MAC deposition and AP-mediated hemolysis (see Example 2); thus, the method of claim 27 is enabled.
SEQ ID NO: 19 Alignment
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SEQ ID NO: 27 Alignment
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238
648
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Conclusion
Claims 27, 31, and 44-47 are allowed.
Claims 25, 26, 32-42, and 48 are rejected.
THIS ACTION IS MADE FINAL. 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.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to DANAYA L MIDDLETON whose telephone number is (571)270-5479. The examiner can normally be reached M-F 9:30AM - 6PM with flex.
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, Vanessa Ford can be reached at (571) 272-0857. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/DANAYA L MIDDLETON/Examiner, Art Unit 1674
/VANESSA L. FORD/Supervisory Patent Examiner, Art Unit 1674
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