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 .
Claims Status
The amendments and remarks filed 06/26/2025 are acknowledged.
Claims 1-53, 55, 64-65, 67-68, 73-75, 85-86, 95, 98, 100-105, and 108-110 are canceled.
Claims 70-71 and 87-88 are amended.
Applicant’s election of Group I without traverse, claims 54, 56-63, 66, 69-72, 76-84, 87-92, 99, and 111-125, in the response filed on 06/26/2025 is acknowledged. Applicant’s election of the following species without traverse in the response filed on 06/26/2025 is acknowledged: SEQ ID NOs: 229-231 for the VH CDRs 1-3, the fusion protein having the structure set forth in instant claim 60, L234A, L235A, and G237A for the amino acid substitutions in the antibody heavy chain, H16E, R38E, F42A, and C125A substitutions for the mutant IL-2 polypeptide, SEQ ID NO: 297 for the IL-2 polypeptide, L234A, L235A, and G237A for the amino acid substitutions of the Fc domains, SEQ ID NO: 389 for the sequence of the linker, and SEQ ID NOs: 334-336 for the first-fourth polypeptide chains of the fusion protein.
Upon further consideration, the restriction requirement between Groups I, II, and III, as set forth in the Office action mailed on 03/26/2025, is withdrawn in its entirety.
In view of the above noted withdrawal of the restriction requirement, applicant is 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Once a restriction requirement is withdrawn, the provisions of 35 U.S.C. 121 are no longer applicable.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.
Additionally, the elected species above is found to be free of the art. Therefore, the election of species requirement is withdrawn.
Thus, claims 54, 56-63, 66, 69-72, 76-84, 87-94, 96-97, 99, 106-107, and 111-149 are pending and under examination.
Priority
Applicant’s claim for the benefit of a prior-filed application under 35 U.S.C. 119(e) or under 35 U.S.C. 120, 121, 365(c), or 386(c) is acknowledged. Applicant has not complied with one or more conditions for receiving the benefit of an earlier filing date
under 35 U.S.C.119(e) as follows:
The later-filed application must be an application for a patent for an invention which is also disclosed in the prior application (the parent or original nonprovisional application or provisional application). The disclosure of the invention in the parent application and in the later-filed application must be sufficient to comply with the requirements of 35 U.S.C. 112(a) or the first paragraph of pre-AIA 35 U.S.C. 112, except for the best mode requirement. See Transco Products, Inc. v. Performance Contracting, Inc., 38 F.3d 551, 32 USPQ2d 1077 (Fed. Cir. 1994).
The disclosures of the prior-filed applications, Application Nos. 63/105,162 and 63/121,663, fails to provide adequate support or enablement in the manner provided by 35 U.S.C. 112(a) or pre-AIA 35 U.S.C. 112, first paragraph for one or more claims of this application. Regarding claims 54 and 123, there is no description of the specific CDRs.
Therefore, the effective filing date of claims 54, 56-63, 66, 69-72, 76-84, 87-94, 96-97, 99, 106-107, and 111-149 is 05/19/2021, the date that application 63/190,669 was filed. If applicant disagrees with the examiner’s factual determination above, application should point out the places within applications 63/105,162 and 63/121,663 where the relevant limitations are described in the manner required by 35 USC 112(a).
Information Disclosure Statement
The information disclosure statements (IDS) submitted on 08/29/2024 and 06/26/2025 are in compliance with the provisions of 37 CFR 1.97. Accordingly, the information disclosure statements are being considered by the examiner.
Notably, the disclosure statement filed lists a Search Report. The listing of the references cited in a Search Report itself is not considered to be an information disclosure statement (IDS) complying with 37 CFR 1.98. 37 CFR 1.98(a)(2) requires a legible copy of: (1) each foreign patent; (2) each publication or that portion which caused it to be listed; (3) for each cited pending U.S. application, the application specification including claims, and any drawing of the application, or that portion of the application which caused it to be listed including any claims directed to that portion, unless the cited pending U.S. application is stored in the Image File Wrapper (IFW) system; and (4) all other information, or that portion which caused it to be listed. In addition, each IDS must include a list of all patents, publications, applications, or other information submitted for consideration by the Office (see 37 CFR 1.98(a)(1) and (b)), and MPEP § 609.04(a), subsection I. states, "the list ... must be submitted on a separate paper." Therefore, the references cited in the Search Report have not been considered. Applicant is advised that the date of submission of any item of information or any missing element(s) will be the date of submission for purposes of determining compliance with the requirements based on the time of filing the IDS, including all "statement" requirements of 37 CFR 1.97(e). See MPEP § 609.05(a).
Note: If copies of the individual references cited on the Search Report are also cited separately on the IDS (and these references have not been lined-through) they have been considered.
Drawings
The drawings are objected to for the following reasons: Figures 2A-2C, 3A-3C, 7, 8A-8C, 9, 12, 13A-13B, 14A-14C, 16A, 17A, and 17C-17E comprise multiple panels. 37 CFR 1.84(u) states that the different views must be numbered in consecutive Arabic numerals and that “partial view intended to form one complete view, on one or several sheets, must be identified by the same number followed by a capital letter.” Each panel should be separately numbered. 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 Objections
Claims 137 and 149 are objected to as being dependent upon a rejected base claim (i.e. claims 136 and 148, respectively) but would be allowable if rewritten in independent form including all of the limitations of the base claim and any intervening claims.
Claim Rejections - 35 USC § 112(a)
Written Description
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 54, 56-63, 66, 69-72, 76-84, 87-91, 93-94, 96-97, 99, 106-107, 111-113, 115-116, 123-131, 136-143, and 148-149 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.
The claims are drawn to a fusion protein, comprising (a) a first moiety comprising a human antibody or antigen-binding fragment thereof that specifically binds CD8b, wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain and (b) a second moiety comprising an IL-2 polypeptide; wherein the first moiety is fused to the second moiety directly or via a linker.
The claims encompass human antibodies. However, the specification teaches that the antibodies of the invention were obtained from either humanization of mouse antibodies or in vitro phage display system [see 0159 of the instant specification], but does not specify what type(s) of cell(s) were utilized in the phage library method to produce the antibodies.
There is no disclosure of a fully human antibody nor any expectation that a human antibody would comprise the same complementary determining regions (CDRs)
as those disclosed in the instant application. One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian fibroblast growth factors (FGFs) were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. In the same manner, disclosure of only humanized sequences provides no salient information regarding the sequences produced in a human.
Accordingly, as applicant does not appear to be in possession of a fully human antibody with the claimed sequences, the disclosure as a whole fails to adequately describe a human antibody. Thus, a claim to such an antibody fails to meet the written description requirements.
Enablement
Claims 106, 130, 136, 142, and 148 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 a viral infection, does not reasonably provide enablement for treating any 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 make and use the invention commensurate in scope with these claims.
As a general rule, enablement must be commensurate with the scope of claim language. MPEP 2164.08 states, “The Federal Circuit has repeatedly held that “the specification must teach those skilled in the art how to make and use the full scope of the claimed invention without undue experimentation’.” In re Wright, 999 F.2d 1557, 1561, 27 USPQ2d 1510, 1513 (Fed. Cir. 1993)” (emphasis added). The “make and use the full scope of the invention without undue experimentation” language was repeated in 2005 in Warner-Lambert Co. v. Teva Pharmaceuticals USA Inc., 75 USPQ2d 1865, and
Scripps Research Institute v. Nemerson, 78 USPQ2d 1019 asserts: “A lack of enablement for the full scope of a claim, however, is a legitimate rejection.” The principle was explicitly affirmed most recently in Auto. Tech. Int’l, Inc. v. BMW of N. Am., Inc., 501 F.3d 1274, 84 USPQ2d 1108 (Fed. Cir. 2007), Monsanto Co. v. Syngenta Seeds, Inc., 503 F.3d 1352, 84 U.S.P.Q.2d 1705 (Fed. Cir. 2007), and Sitrick v.
Dreamworks, LLC, 516 F.3d 993, 85 USPQ2d 1826 (Fed. Cir. 2008). See also In re Cortright, 49 USPQ2d 1464, 1466 and Bristol-Myers Squibb Co. v. Rhone-Poulenc Rorer Inc., 49 USPQ2d 1370.
The factors to be considered in determining whether a disclosure meets the enablement requirement of 35 U.S.C. 112, first paragraph, have been described in In re Wands, 8 USPQ2d 1400 (Fed. Cir. 1988). Among these factors are: (1) the nature or the invention; (2) the state of the prior art; (3) the relative skill of those in the art; (4) the predictability or unpredictability of the art; (5) the breadth of the claims; (6) the amount of direction or guidance presented; (7) the presence or absence of working examples; and (8) the quantity of experimentation necessary. When the above factors are weighed, it is the examiner’s position that one skilled in the art could not practice the invention without undue experimentation. Some experimentation is not fatal; the issue is whether the amount of experimentation is “undue”; see In re Vaeck, 20 USPQ2d 1438, 1444.
(1) The nature of the invention and (5) The breadth of the claims:
The claims are drawn to a method of treating infection comprising administering to an individual in need thereof an effective amount of a composition comprising a fusion protein comprising a human antibody or antigen-binding fragment thereof that specifically binds CD8b and an IL-2 polypeptide. Claims 107, 131, 137, 143, and 149 add the limitation, respectively, of wherein the infection is a viral infection.
The claims are broad an inclusive of any type of infection. The breadth of the claim exacerbates the complex nature of the subject matter to which the present claims are directed. The claims are extremely broad due to the vast number of possible types of infection. There is no support provided in the instant specification or in the prior or instant art that teaches or supports the ability to treat any infection encompassed by these broad claims.
(2) The state of the prior art and (4) The predictability or unpredictability of the art:
While the state of the art is relatively high with regard to treatment of specific types of infections, the state of the art with regard to treating any infection is underdeveloped. The instant specification itself does not teach any method or treatment that would treat any infection. It is known in the prior art that infections caused by bacteria, viruses, fungus, and parasites differ in their treatments, and may not respond to treatment at all. Mayo Clinic, 2025 (instant PTO-892) teaches that antibiotics are the treatment for infections caused by bacteria, but that bacteria can develop antibiotic resistance making infections caused by these bacteria difficult to treat [see page 4]. Further, Mayo Clinic teaches antivirals are the treatment for certain infections caused by viruses, antifungals are the treatment for fungal infections, and anti-parasitics are often the treatment for infections caused by parasites, but that some parasites have developed resistance to the drugs [see pages 4-5].
The art, however, does teach that CD8b enhances T-cell receptor affinity and signaling, which underpin effective cytotoxic responses against virally infected cells (i.e. treat viral infections) [see page 1 of Harmonizome, 2013; instant PTO-892). The examples in the instant specification demonstrate that the fusion proteins activate CD8b+ cells [0136] and enhance T cell activation [see Examples]. Thus, this supports enablement for a method of treating a viral infection comprising administering to an individual in need thereof an effective amount of a composition comprising a fusion protein comprising an antibody or antigen-binding fragment thereof that specifically binds CD8b, and an IL-2 polypeptide, as encompassed by instant claims 107, 131, 137, 143, and 149.
(6) the amount of direction or guidance presented; (7) the presence or absence of working examples:
There is a lack of working examples in the specification for treating all types of infections encompassed by the instant claims. Applicant has not provided any substantive evidence of treating any infection using the claimed methods. Because the infections encompassed by the instant claims are so disparate, and no single infection can be representative of all other encompassed infections, a demonstration of treatment or support of a given condition does not provide support for the breadth of the claim.
In conclusion, the claimed invention does not provide enablement for treating all types of infection encompassed by the instant claims. Thus for the reasons outlined above, the specification is not considered to be enabling for one skilled in the art to make and use the claimed invention as the amount of experimentation required is undue, due to the broad scope of the claims, and the lack of guidance and working examples provided in the specification. Therefore, the specification is not representative of the instant claims and the specification is not fully enabled for the instant claims. In view of the above, one of skill in the art would be forced into undue experimentation to practice the claimed invention.
Concluding Remarks
The Examiner considered the written description of the genus of mutant IL-2 polypeptides that have a binding affinity to IL-2Rα, IL-2Rβ, and IL-2Rγ that is reduced by 50% or more when compared to the binding affinity of a wild-type IL-2 polypeptide, as claims in instant claims 77-78, because the mutant IL-2 is defined solely by function. However, the mutations, as defined in claim 80, are within this genus, and are therefore representative of the genus, thus meeting the requirements for written description.
Allowable Subject Matter
The art does not teach an antibody or antigen-binding fragment thereof that specifically binds CD8b, wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises SEQ ID NOs: 229-231 for the CDR-H 1-3 and wherein the VL domain comprises SEQ ID NOs: 40-42 for the CDR-L 1-3, as encompassed by instant claims 54, 92, and 114, or wherein the antibody or fragment comprises a heavy chain variable (VH) domain and a light chain variable (VL) domain, wherein the VH domain comprises SEQ ID NOs: 240-242 for the CDR-H 1-3 and wherein the VL domain comprises SEQ ID NOs: 40-42 for the CDR-L 1-3, as encompassed by instant claims 92, 114, and 123. Additionally, the Examiner completed a reverse translation search of the respective CDRs to a nucleotide sequence. The art also did not teach polynucleotide sequences encoding the specific combination of CDRs.
Conclusion
Claims 92, 114, 117-122, 132-135, and 144-147 are allowed. Claims 54, 56-63, 66, 69-72, 76-84, 87-91, 93-94, 96-97, 99, 106-107, 111-113, 115-116, 123-131, 136-143, and 148-149 are not allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Brittney E Donoghue whose telephone number is (571)272-9883. The examiner can normally be reached Mon - Fri 7:30 - 3:30.
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, 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.
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/B.E.D./Examiner, Art Unit 1675
/JEFFREY STUCKER/Supervisory Patent Examiner, Art Unit 1675