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 03/30/2026, are acknowledged.
Claims 2 and 16-19 are canceled.
Claims 1, 3-11, and 13-14 are amended.
Claim 25 is new.
Claims 1, 3-15, and 20-25 are pending.
Claims 1, 3-15, 20, and 24-25 are directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(B), claims 21-23, directed to the process of making or using an allowable product, previously withdrawn from consideration as a result of a restriction requirement, are hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because all claims previously withdrawn from consideration under 37 CFR 1.142 have been rejoined, the restriction requirement as set forth in the Office action mailed on 07/14/2025 is hereby withdrawn. In view of the withdrawal of the restriction requirement as to the rejoined inventions, applicant(s) are advised that if any claim presented in a divisional application is anticipated by, or includes all the limitations of, a claim that is allowable in the present application, such claim may be subject to provisional statutory and/or nonstatutory double patenting rejections over the claims of the instant application. Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable. See In re Ziegler, 443 F.2d 1211, 1215, 170 USPQ 129, 131-32 (CCPA 1971). See also MPEP § 804.01.
As such, claims 1, 3-15 and 20-25 are pending examination and currently under consideration for patentability under 37 CFR 1.104.
DETAILED ACTION
Withdrawn Objections
The sequence disclosure objections are withdrawn. Issues regarding missing incorporation by reference paragraph and sequences not identified by sequence identifier in the specification have been sufficiently addressed through amendments to the specification on 03/30/2026.
The specification objections are withdrawn. Issues regarding minor informalities and trademarks/names have been sufficiently addressed through amendments to the specification on 03/30/2026.
The claim objections are withdrawn. Issues regarding minor informalities have been sufficiently addressed through amendments to the claims filed on 03/30/2026.
Withdrawn Rejections
Applicant’s arguments, see pages 15 and 16, filed 03/30/2026, with respect to claims 1-15, 20 and 24 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. Further, Examiner acknowledges that claim 2 is canceled thus rendering the rejection moot. As such, the rejection under 35 USC 112(b) is withdrawn.
Applicant’s arguments, see pages 16 and 17, filed 03/30/2026, with respect to claims 1, 4-9, 12-15, 20, and 24 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 large genus of pertussis toxin-binding proteins have been sufficiently addressed through amendments to the claims. As such, the rejection under 35 USC 112(a) is withdrawn.
New Objections Necessitated by Amendment
Claim Objections
Claim 5 is objected to because of the following informalities:
Claim 5: “… at least 80% sequence identity to of any one of SEQ ID NOs: 40-52” should read “… at least 80% sequence identity to .
Appropriate correction is required.
New 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 22 and 23 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.
Claim 22 is drawn to a method for preventing Bordetella pertussis infection in a subject, the method comprising administering to the subject an effective amount of the pertussis toxin-binding protein of claim 1. Infection occurs when a pathogen enters the body, and disease can result from the infection. To prevent infection would mean preventing the pathogen from entering the body. The specification does not indicate that the composition can form a physical barrier to prevent a pathogen from entering the body. Therefore, the claim scope regarding the “prevention” is indefinite.
Claim 23 recites the limitation "the control sample" in lines 3 and 7. There is insufficient antecedent basis for this limitation in the claim.
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.
Claim 22 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 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 preventing Bordetella pertussis infection comprising administering to the subject an effective amount of the pertussis toxin-binding protein. 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 or preventing Bordetella pertussis infection with VHH immunoglobulins. The art teaches there are drawbacks to VHH therapeutics. Mei et al (Front. Pharmacol. (2022) 13:963978) teach that there remains a challenge with designing optimal nanobody combinations and forms (see page 7, right col.). Mei et al disclose that bispecific nanobodies are superior to bivalent form of a single nanobody; combining the most therapeutically effective monovalent nanobodies does not necessarily produce bispecific nanobodies with superior performance, while a dual complementary site structure constructed from less therapeutically effective nanobodies may exert a better therapeutic effect (see page 7, right col.). Further, Bocancia-Mateescu et al (Pharmaceuticals 2023, 16, 863) disclose that the size of nanobodies can lead to rapid kidney elimination due to their molecular mass below threshold of glomerular filtration; the extended CDR3 loops of nanobodies can create unwanted complexations; due to their single domain nature, there can be difficulty in binding small antigens; and, to ensure the safety of the therapeutic, the nanobody would need to be humanized (see Table 1). As such, their remains unpredictability with VHH/nanobody therapeutics because the design of the VHH can completely affect the function.
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 for preventing Bordetella pertussis infection comprising administering to the subject an effective amount of the pertussis toxin-binding protein.
The working examples provided by Applicant do not demonstrate a method of preventing Bordetella pertussis infection comprising administering to the subject an effective amount of the claimed pertussis toxin-binding proteins. Applicant tested the efficacy of Fc fusion protein of the PT tetravalent antibodies in vitro (see Example 6). In one study, Applicant determined the survival rate for single dose and multiple dose administration in mice injected with PT toxin (i.e., challenged mouse model) (see Example 6.1; Table 12). For single dose and multiple dose administration, the survival rate of mice was significantly increased when iPT15n12FC and iPT12diFC were administrated at 40 ug/dose as compared with at 20 ug/dose, and there was no significant difference among other antibodies (see Figures 1-4 and Table 12). In another study, Applicant determined the survival of mice by first weighing the mice, measuring the numbers of white blood cells and lymphocytes, and injected pertussis Bacillus into the mice thus establishing a challenged mouse model (see Example 6.2). FC fusion proteins of PT tetravalent antibody iPT7n15FC, iPT42n7FC, iPT15n12Fc, iPT42n12Fc and iPT12ndiFc were injected into the challenged mouse model and mouse mortality was recorded every day (see Example 6.2; Table 13). All antibodies had protective effect on the challenge mice, among which the antibodies iPT7n15FC and iPT42n7FC had good protective effect, the survival rate of mice was significantly higher when administered iPT7n15FC and iPT15n12FC at 40 ug/dose than at 20 ug/dose (see Table 13; Figure 5).
Because the specification only studied mouse models treating PT toxin, one cannot assume that the method of preventing will work similarly to the mouse 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 preventing would result in therapeutic response as recited in the claims.
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.
Allowable Subject Matter
The combination of CDR sequences recited in claim 1, and consequent VHH sequences, appear to be free of the art. The closest prior art is WO 2011/051327 A2 (publication date: 05/05/2011; previously submitted with the Office Action mailed 10/30/2025) which teach of small antibody-like single chain proteins that comprise a bottomside epitope binding domain comprising four bottomside binding regions and this epitope binding domain is in addition to the topside epitope binding domain formed by the three CDRs (see Abstract). Specifically, the ‘327 document disclose of SEQ ID NO: 36 which shares 49.8% identity with instant SEQ ID Nos: 4-6 (see alignment below).
SEQ ID NO: 36 Alignment
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Conclusion
Claims 1, 3-4, 6-15, 20-21, and 24-25 are allowed.
Claims 22 and 23 are rejected.
Claim 5 is objected to.
Applicant's amendment necessitated the new ground(s) of rejection presented in this Office action. Accordingly, THIS ACTION IS MADE FINAL. See MPEP § 706.07(a). 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.
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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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