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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in
37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on November 7, 2025 has been entered.
Election/Restrictions
Claim 1 is directed to an allowable product. Pursuant to the procedures set forth in MPEP § 821.04(b), claims 23-25 and 28-30, directed to the process of making or using the allowable product, previously withdrawn from consideration as a result of a restriction requirement, is hereby rejoined and fully examined for patentability under 37 CFR 1.104.
Because a claimed invention previously withdrawn from consideration under 37 CFR 1.142 has been rejoined, the restriction requirement between Groups I - III and Species (C)-(D) as set forth in the Office action mailed on 11/21/2024 is hereby withdrawn.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Once the restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable.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.
Claim Status
Claim listing filed on November 7, 2025 is pending. Claims 7, 11-17, 21, and 27 are canceled. Claims 1-5, 9-10, 18, and 25 are amended. Claims 35-75 are new. Claims 1-6, 8-10, 18-20, 22-26, and 28-75 are examined upon their merits.
Information Disclosure Statement
The information disclosure statements filed on 11/07/2025 and 11/14/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Withdrawn Claim Rejections
The rejection of Claims 1-6, 8-10, 18-20, 22, 26, and 31-34 under 35 U.S.C. 112(b) as being indefinite is withdrawn in view of Applicant’s amendments to Claims 1-4. It is clear that the claims are directed to a fusion protein comprising a mutant IL-2 polypeptide comprising SEQ ID NO: 1 with amino acid substitutions H16E, R38E, F42A, and C125A.
The rejection of Claims 1-6, 8-10, 19-20, 22, 26, and 31-34 on the ground of nonstatutory double patenting as being unpatentable over Claims 1-2, 4-38, and 41-45 of U.S. Patent No. 12,024,559 is withdrawn in view of the terminal disclaimer filed on November 7, 2025.
Specification (New)
The disclosure is objected to because of the following informalities:
Paragraph [0076], line 8 recites “uterine cancer, ,” wherein the second comma should be deleted to recite “uterine cancer,”
Table 4 on page 66 recites “foraat C” in the first row wherein “format C” is correct.
Appropriate correction is required. Applicant is urged to carefully review the specification for additional informalities.
Drawings (New)
The drawings are objected to because the “Wild-type IL-2 polypeptide” and “Mutant IL-2 polypeptide” symbols in Fig. 3 are the same (as shown below). Based on the figure, Examiner believes that the “Wild-type IL-2 polypeptide” symbol is intended to have the black dots removed.
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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.
Claim Rejections - 35 USC § 112 (New)
Claims 18, 39, 45, and 51 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 18, 39, 45, and 51 are rejected for recitation of intended results/effects that do not confer some structural, material, or manipulative difference on the scope of the parent claim. The claims recite wherein the fusion protein binds human CD8β, and wherein the binding of the fusion protein to CD8β does not block the interaction of CD8β with MHC class I. It is unclear how these claims further structurally limit the scope of the parent claims. The specification teaches that the anti-CD8β antibody xmCD8ab2 blocks MHC wherein the anti-CD8β antibody xmCD8ab3 does not block MHC (paragraph [0151]). This teaching demonstrates that MHC blocking/non-blocking varies between anti-CD8β antibodies, and without known structure-to-function correlation, it is unclear what anti-CD8β structures are MHC non-blocking. The specification further teaches that whether an anti-CD8 antibody or fusion protein blocks the interaction of CD8 with MHC class I can be assayed, e.g. by assaying activation status of CD8+ T cells in the presence or absence of the anti-CD8 antibody or fusion protein (paragraph [0098]). Thus, experimental assays would be required to determine what fusion proteins are capable of binding/not binding MHC class I. MPEP 2173.05(g) states: “the use of functional language in a claim may fail ‘to provide a clear-cut indication of the scope of the subject matter embraced by the claim' and thus be indefinite.” It further states: “Examiners should consider the following factors when examining claims that contain functional language to determine whether the language is ambiguous: (1) whether there is a clear cut indication of the scope of the subject matter covered by the claim; (2) whether the language sets forth well-defined boundaries of the invention or only states a problem solved or a result obtained; and (3) whether one of ordinary skill in the art would know from the claim terms what structure or steps are encompassed by the claim” (emphasis added). Since the claims fail to meet all (3) criteria set forth in MPEP 2173.05(g), Claims 18, 39, 45, and 51 are rejected for indefiniteness.
Note, Claims 6, 8-10, 22, 31-34, 36-38, 42-44, and 48-50 are interpreted as inherent properties of the structures outlined in the parent claims (MPEP § 2112.01).
Note, the variable heavy chain domains and variable light chain domains that bind to an epitope on human CD8β as defined in Claims 1-3 and the antigen-binding domain that binds to an epitope on human CD8β as defined in Claim 4 are interpreted to comprise the structures outlined in the specification and those known in the art prior to filing. For example, an anti-CD8β antibody termed 5F2 was known in the art as early as 1991 as evidenced by DiSanto et al. J. Immun. Methods 1991 (of record in IDS). It is of record in the non-final office action filed 03/31/2025 that Strittmatter-Keller et al. PLoS One. 2018 (of record) teaches that an anti-CD8β antibody (SIDI8BEE) was commercially available before the effective filing date of the claimed invention. Kley et al. US 2019/0071500 (published March 7, 2019) teaches that non-antibody CD8β-binding domains (such as affimers, aptamers, or DARPins) were also known in the art prior to filing (paragraph [0038]).
Claim Rejections - 35 USC § 112 (New, necessitated by amendment)
Claims 28, 57, 65, and 73 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 treating cancer by administering the fusion protein of Claims 1-4, does not reasonably provide enablement for treating any type of chronic infection. The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to use the invention commensurate in scope with these claims.
MPEP § 2164.01(a) states that 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, 8 USPQ2d, 1400 (CAFC 1988) and MPEP 2164.01.
The breadth of the claims and nature of the invention:
The nature of the invention is complex, encompassing the treatment of any chronic infection. Note, “treating” is not defined in the specification and is interpreted as alleviating the symptoms or complications of an established disease, delaying the progression of an established disease, and/or curing or eliminating an established disease. “Chronic infection” is not defined in the specification, and the broadest reasonable interpretation encompasses any long-lasting or persistent infection caused by an agent such as a virus, bacteria, or parasite wherein the infection can be symptomatic or asymptomatic. Non-limiting examples of chronic infections are Human Immunodeficiency Virus (HIV), Hepatitis B and C, tuberculosis, lyme disease, etc.
When analyzing the scope of enablement, the claims are analyzed with respect to the teachings of the specification and are to be "given their broadest reasonable interpretation consistent with the specification." See MPEP 2111 [R-5]; Phillips v. AWH Corp., 415 F.3d 1303, 75 USPQ2d 1321 (Fed. Cir. 2005); and In re Hyatt, 211 F.3d 1367, 1372, 54 USPQ2d 1664, 1667 (Fed. Cir. 2000). Applicant always has the opportunity to amend the claims during prosecution, and broad interpretation by the examiner reduces the possibility that the claim, once issued, will be interpreted more broadly than is justified. In re Prater, 415 F.2d 1393, 1404-05, 162 USPQ 541, 550- 51 (CCPA 1969).
The state of the prior art and level of predictability in the art:
The level of predictability in the art depends, most importantly, on whether the claimed invention can be practiced by one of ordinary skill in the art. There is no support in the art that a single agent can treat any type of chronic infection. Infectious diseases are caused by vastly different pathogens (such as bacteria, viruses, fungi, and parasites) that require specific treatments (such as antibiotics, antivirals, antifungals, or antiparasitics) to combat the diverse disease etiologies. The state of the art shows a lack of predictability in administering a single agent to treat any type of chronic infection, and there is no support in the Applicant’s disclosure leading one of ordinary skill to overcome the lack of predictability.
Level of skill in the art:
The level of skill would be high encompassing immunology, virology, microbiology, epidemiology, etc.
Amount of direction provided by inventor and the existence of working examples:
The specification demonstrates anti-tumor efficacy of fusion proteins comprising (i) anti-CD8β antibodies and (ii) IL-2 mutants comprising mutations that reduce binding to both IL-2Rα and IL-2Rβγ in melanoma mouse models and colorectal cancer mouse models (Examples 4-7). However, there are no examples of administering the fusion proteins to treat any type of chronic infection.
A person having ordinary skill in the art would have to make a substantial inventive contribution in order to treat any type of chronic infection, since there is no guidance within the disclosure as filed pertaining to this embodiment.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure:
Given that the nature of the claims is in vivo treatment, a person having ordinary skill in the art would have to perform multiple further experiments, in human clinical trials or in animal models, that are predictive of treatment in a representative number of chronic infections in order to demonstrate the invention could be used with a reasonable expectation of success. The amount of experimentation required for enabling guidance, commensurate in scope with what is claimed, goes beyond what is considered ‘routine' within the art, and constitutes undue further experimentation in order to use the treatment with a reasonable expectation of success.
The instant specification does not enable the invention to treat chronic infection (Claims 28, 57, 65, and 73).
Double Patenting (Maintained)
1. Claims 1-6, 8-10, 19-20, 22-26, 28, 31-38, 40-44, 46-50, 52-57, 60-65, and 68-73 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 54, 56, 58-63, 66, 69-72, 76-84, 87-94, 96-97, 99, 106, and 111-123 of copending U.S. App. No. 18/662,910 (of record). Note, the rejection of record applies to Claims 1-6, 8-10, 19-20, 22, 26, and 31-34 and now applies to Claims 1-6, 8-10, 19-20, 22-26, 28, 31-38, 40-44, 46-50, 52-57, 60-65, and 68-73 due to Applicant’s amendments.
Applicant's arguments filed November 7, 2025 have been fully considered but they are not persuasive. Applicant argues that the ‘910 application has a later patent term filing date than the instant application, and it would be appropriate to withdraw the instant provisional nonstatutory double patenting rejection if it is the only rejection remaining of record. Because the provisional nonstatutory double patenting rejection is not the only rejection remaining in the instant application, the rejection is maintained.
2. Claims 1-6, 8-10, 22, 26, 28-29, 31-34, 36-38, 42-44, 48-50, 56-58, 64-66, and 72-74 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 1-3, 15-25, 52-53, 60-63, 65-69 of copending U.S. App. No. 18/859,452 (of record). Note, the rejection of record applies to Claims 1-5, 8-10, 26, and 31 and now applies to Claims 1-6, 8-10, 22, 26, 28-29, 31-34, 36-38, 42-44, 48-50, 56-58, 64-66, and 72-74 due to Applicant’s amendments.
Applicant's arguments filed November 7, 2025 have been fully considered but they are not persuasive. Applicant argues that the ‘452 application has a later patent term filing date than the instant application, and it would be appropriate to withdraw the instant provisional nonstatutory double patenting rejection if it is the only rejection remaining of record. Because the provisional nonstatutory double patenting rejection is not the only rejection remaining in the instant application, the rejection is maintained.
Allowable Subject Matter
Claims 30, 59, 67, and 75 are objected to as being dependent upon a rejected base claim, but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims. Note, if the 112(b) and 112(a) rejections of record are overcome, the provisional nonstatutory double patenting rejections of record would be withdrawn.
Conclusion
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SARAH COOPER PATTERSON whose telephone number is (703)756-1991. The examiner can normally be reached Monday - Friday 8:00am - 5:00pm EST.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Jeffrey Stucker can be reached on (571) 272-0911. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/SARAH COOPER PATTERSON/Examiner, Art Unit 1675
/STACEY N MACFARLANE/Examiner, Art Unit 1675