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 the species (A)-(T) in the reply filed on August 11, 2025 is acknowledged. Applicant states that claims 1, 3, 36, 54, 56, 82, 85, 87-88, 90, 93-94, 96 and 100-109 read upon the elected species.
2. Claims 92 and 97-98 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on August 11, 2025.
3. Claims 1, 3, 36, 54, 56, 82, 85, 87-88, 90, 93-94, 96 and 100-109 are under examination in the current office action.
Information Disclosure Statement
4. The information disclosure statements (IDSs) file 09/07/2022, 08/03/2023, and 09/30/2024 have been considered and the references therein are of record.
Specification
5. The disclosure is objected to because of the following informalities:
In the description of the drawings for Figure 10A-10H (p. 5 lines 14-19), it states that “Fig. 10F shows a sensorgram of EP03; Fig. 10G shows a sensorgram of EPIM-06”. However, in the drawings, Fig. 10F is labeled as “EP003” and Fig. 10G is labeled “EP006”. Appropriate correction is required
Similarly, in the description of the drawings for Figs. 12A-12D, the specification states “EP0001” and “EP0003” at p. 5 lines 27 and 28, respectively. In contrast, in the drawings Fig. 12B is labeled “EP001” and Fig. 12C is labeled “EP003”. Appropriate correction is required.
Claim Objections
6. Claim 82 is objected to because of the following informalities: the amendment to claim 82 (deleting the second “at”) inadvertently created a grammatical issue in the claim. The claim should be amended to revert back to its original language, reciting “…comprising a substitution at at least one of positions K35, R38, F42, and Y45…” in order for the claim to make grammatical sense (i.e., there is a substitution present within at least one of the listed positions). 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. Claims 3, 36, 87, 96 and 108 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 3 recites that “X5 is selected from I, L, T, and V”. X5 is defined as an uncharged, nonpolar residue according to claim 1. However, according to the instant specification (p. 12 lines 5-9), threonine (T) is not defined as an uncharged nonpolar residue but rather as an uncharged polar residue (p. 12, lines 3-4). Therefore, it is unclear whether T is meant to be included within the listing for X5, or if instead the description for X5 in claim 1 is incorrect. The claim is therefore indefinite.
Claims 36 and 87 each recite a selection of polypeptide sequences. However, in line 10 of claim 36 (“…(SEQ ID NO: 20): and…”) and line 26 of claim 87 (“…(SEQ ID NO: 20); and…) there is an extra “and” in the middle of the listing of sequences. This recitation renders the claims indefinite because it is unclear how it affects the selection of the sequence. Is a sequence selected from the first grouping of sequences prior to the “and” and a second grouping of sequences following the “and”? Are all of the sequences in the first grouping prior to the “and” and all of the sequences in the second grouping of sequences following the “and” each considered a selection (i.e., the entire group is a selection)? The metes and bounds of the claim therefore cannot be readily determined.
Claim 96 contains the trademark/trade name Nanobody®. Where a trademark or trade name is used in a claim as a limitation to identify or describe a particular material or product, the claim does not comply with the requirements of 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph. See Ex parte Simpson, 218 USPQ 1020 (Bd. App. 1982). The claim scope is uncertain since the trademark or trade name cannot be used properly to identify any particular material or product. A trademark or trade name is used to identify a source of goods, and not the goods themselves. Thus, a trademark or trade name does not identify or describe the goods associated with the trademark or trade name. In the present case, the trademark/trade name is used to identify/describe a single-domain or VHH antibody and, accordingly, the identification/description is indefinite.
Claim 107 recites a method of treating a disease, wherein the disease comprises cancer or immunosuppression. However, “immunosuppression” is not, per se, a disease but rather a condition or symptom that is the result of a disease or disorder, or else a side effect of a drug or treatment. The metes and bounds of the claim therefore cannot be fully determined.
The following is a quotation of 35 U.S.C. 112(d):
(d) REFERENCE IN DEPENDENT FORMS.—Subject to subsection (e), a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
The following is a quotation of pre-AIA 35 U.S.C. 112, fourth paragraph:
Subject to the following paragraph [i.e., the fifth paragraph of pre-AIA 35 U.S.C. 112], a claim in dependent form shall contain a reference to a claim previously set forth and then specify a further limitation of the subject matter claimed. A claim in dependent form shall be construed to incorporate by reference all the limitations of the claim to which it refers.
8. Claim 3 is rejected under 35 U.S.C. 112(d) or pre-AIA 35 U.S.C. 112, 4th paragraph, as being of improper dependent form for failing to further limit the subject matter of the claim upon which it depends, or for failing to include all the limitations of the claim upon which it depends. As discussed above, claim 3 is drawn to an engineered IL2 polypeptide, wherein X5 is selected from I, L, T, and V. However, claim 1 (from which claim 3 depends) recites that X5 is an uncharged, nonpolar residue, and according to the specification (p. 12), T (threonine) is not defined as an uncharged, nonpolar residue. Accordingly, the scope of claim 3 fails to further limit the scope of claim 1 with respect to the residue T.
Applicant should note the “Infringement Test” for dependent claims in MPEP 608.01(n). The test for a proper dependent claim is whether the dependent claim includes every limitation of the parent claim. A proper dependent claim shall not conceivably be infringed by anything which would not also infringe the basic claim. In the instant case, the IL2 polypeptide of claim 3 that comprises a T at X5 could be infringed without infringing the claim from which it depends, i.e., claim 1. Therefore, the claim is improperly dependent.
Applicant may cancel the claim(s), amend the claim(s) to place the claim(s) in proper dependent form, rewrite the claim(s) in independent form, or present a sufficient showing that the dependent claim(s) complies with the statutory requirements.
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.
9. Claim 107 is 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 cancer or an immunosuppressive disorder in a subject in need thereof, does not reasonably provide enablement for a method of treating any disease 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 make and use 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).
Claim 107 is broadly drawn to a method of treating a disease in as subject in need thereof, comprising administering an effective amount of an engineered IL2 polypeptide of claim 1 to the subject. Claim 107 thus encompasses the treatment of any disease in a subject in need thereof, which method is not fully enabled by the specification.
The instant specification at p. 1 discloses that interleukin-2 (IL2) “is cytokine that modulates lymphocyte proliferation and activation.” The nature of the invention is the disclosure of IL2 polypeptides that are engineered to have improved binding to IL2Rb and/or reduced binding to IL2Ra as compared to wild-type IL2. These engineered IL2Rb agonist polypeptides are disclosed to provide the advantage of increasing stimulation of NK cells and T effector cells compared to wild-type IL2, but not T regulatory cells, and thus “are useful for modulating or activating an immune response, for example, for treatment of cancer.” (p. 10 lines 15-18)
The prior art also recognizes that because of IL2’s potential in stimulating proliferation of the main antitumor immunocytes, namely CD8+ T cells (effector T cells) and natural killer (NK) cells, it is useful in clinical immunotherapy (see, for example, Chen et al. (2018) Cell Death Dis. 9:989, pp. 1-12; listed on 09/07/2022 IDS). Accordingly, the specification reasonably provides enablement for treating a subject having cancer or that is in need of immunoenhancement, such as a subject having an immunosuppressive disease or disorder. However, the scope of the claims covers the treatment of any disease beyond cancer.
For example, there is no evidence of record to support a claim for the treatment of a subject having a neurodegenerative disease, such as Parkinson’s disease or Alzheimer’s disease, or a hereditary disease such as cystic fibrosis or Huntington’s disease. And for diseases that are associated with an overactive immune system, such as in the case of autoimmune diseases and disorders, the presently claimed IL2Rb agonists would likely adversely affect or even exacerbate disease symptoms or progression. The prior art also generally recognizes that the treatment for these types of diseases (i.e., neurodegenerative diseases, hereditary diseases and disorders, autoimmune diseases and disorders, among others) is complex and unpredictable. Accordingly, only those diseases or disorders in which subjects would benefit from the stimulation of NK cells and/or T effector cells would be expected to be amenable to treatment using the presently claimed engineered IL2 polypeptides.
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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
10. Claim(s) 56 and 82 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Ast et al. (US 2012/0244112 A1).
Ast et al. teach mutant IL2 polypeptides that have abolished or reduced affinity for the high-affinity IL-2 receptor (IL2Rabg) (i.e., IL2Ra binding) and preserved affinity to the intermediate-affinity IL-2 receptor (IL2Rbg) (i.e., IL2Rb binding), each compared to a wild-type IL2 polypeptide (see [0014]). Ast teaches that the IL2 mutant comprises a mutation at one or more of positions 35, 38, 42, 43 and 35 ([0014]), which is on point to present claim 56. Ast discloses that the mutant IL2 polypeptide has reduced affinity to the a-subunit of the IL2 receptor by at least 5-fold ([0082]) (i.e., the IL2 polypeptide binds to IL2Ra with at least 2-fold reduced binding kinetics as compared to wild-type IL2).
In particular, Ast teaches that amino acid substitutions can include: K35E, K35A, R38A, R38E, R38N, R38F, R38S, R38L, R38G, R38Y, R38W, F42L, F42A, F42G, F42S, F42T, F42Q, F42E, F42N, F42D, F42R, F42K, K43E, Y45A, Y45G, Y45S, Y45T, Y45Q, Y45E, Y45N, Y45D, Y45R, and Y45K ([0080]). Bolded residues are those listed in present claim 82.
Accordingly, Ast teaches an engineered IL2 polypeptide comprising a an engineered IL2Ra binding region comprising one or more substitutions at residues K35, R38, F42, or Y45 as presently claimed.
11. Claim(s) 1, 3, 88, 90, 93-94, 100-102 and 104-109 is/are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Garcia et al. (US 10,150,802 B2; issued Dec 11, 2018).
Garcia et al. teach human IL-2 muteins or variants thereof that have an increased binding capacity for IL2Rb receptor (CD122) and a decreased binding capacity to IL2Rg receptor (CD32) compared to wild-type IL-2, wherein the IL2 mutein comprises one or more amino acid substitutions that increase IL2Rb binding affinity (col. 3 lines 22-27). Garcia teaches that the amino acid substitutions that increase IL2Rb binding affinity comprise: Q74N, Q74H, Q74S, L80F, L80V, R81D, R81T, L85V, I86V, I89V, and/or I93 or combinations thereof (col. 3 lines 34-37). Note that the residues that are underlined are recited by claim 1, and those that are both underlined and bolded are on point to recited substitutions in claim 3. Garcia teaches that such IL2 muteins can have 10, 15, 20, 25, 50 or more fold greater affinity for the IL2Rb receptor than wild-type IL2 (col. 15 lines 13-16). Thus, the IL2 mutein of Garcia anticipates the engineered IL2 polypeptide of present claims 1 and 3.
Regarding claims 88 and 90, Garcia discloses an IL2 mutein fusion protein comprising one of the IL2 muteins of the invention linked to a human Fc domain (col. 4 lines 43-45), so as to increase the circulating half-life of the fusion protein in vivo (col. 25 lines 15-21). Additional heterologous polypeptides that can increase circulating half-life include human serum albumin (HSA) (col. 25 lines 23-25).
Regarding claim 93, Garcia teaches a chimeric polypeptide that is a fusion protein containing at least a mutant IL2 polypeptide and a heterologous polypeptide (col. 24 lines 15-17).
Regarding claim 94, the chimeric polypeptide can include a mutant IL2 and an antibody or antigen-binding portion thereof as the heterologous polypeptide (col. 26 lines 20-22).
With respect to claims 100-102, Garcia teaches nucleic acid molecules that encode for the IL2 mutein polypeptides of the invention (col. 26 lines 29-51). The nucleic acid molecules can be contained within a vector that is capable of directing their expression (an expression vector comprising the polynucleotide) in a cell that has been transduced with the vector (a modified cell comprising the isolated polynucleotide) (col. 27 lines 28-34).
Regarding claim 104, Garcia teaches a pharmaceutical composition comprising an IL2 mutein of the invention, or an IL2 mutein fusion protein, and a pharmaceutically acceptable carrier (col. 4 lines 46-49).
Finally, regarding claims 105-109, Garcia teaches that the IL2 mutein polypeptides of the invention may be administered in a therapeutically effective amount (col. 36 lines 46-48) to a subject, such as for the treatment of cancer (for example at col. 31 lines 62-64). The type of cancer to be treated can be renal cell carcinoma, melanoma, breast cancer, or lung cancer (col. 12 lines 9-32; col. 31 lines 64-67). The IL2 muteins were found to enhance stimulation of CD8+ T cells (effector T cells) but not regulatory T cells (Fig. 10; col. 6 lines 16-18). Thus, Garcia’s method of administering an IL2 mutein of the invention not only provides for the treatment of a subject having cancer, but also for the modulation of an immune response in a subject, wherein the modulation comprises enhancing effector T cell activity and suppressing Treg cell activity.
12. Claim(s) 1, 3, 54, 56, 82, 88, 90, 93-94, 96, 100-102 and 104-109 is/are rejected under 35 U.S.C. 102(a)(2) as being anticipated by Sahin et al. (WO 2020/020783 A1; filed 19 Jul 2019, with priority to 24 Jul 2018).
Sahin et al. teach IL2 agonist variant polypeptides (also interchangeably referred to as IL2 mutein polypeptides) having one or more amino acid substitutions which reduce the affinity of the alpha subunit of IL2Rabg receptor and one or more substitutions which enhance the affinity for IL2Rbg in comparison to wild-type IL2 (see abstract; p. 3 lines 17-30), which is on point to the functional limitations of present claims 1 and 54. In particular, Sahin discloses that the human IL2 functional variant is substituted at at least one of positions K35, K43, E61 or E62 (p. 5 lines 6-8), which addresses a limitation of present claim 56. For example, position 35 may be substituted with glutamic acid (K35E)(p. 7 lines 16-17), which addresses claim 82(i).
Regarding claims 1 and 3, Sahin teaches that the IL2 mutein may also comprise one or more substitutions that enhance the affinity for IL2Rbg, which comprise substitutions at one or more of positions R81, L85, I86, N88, I92, L94 or E95 (p. 12 lines 1-3). Note that the sequence given by SEQ ID NO: 1 in claim 1 represents residues 81-95 of human IL2. Sahin teaches that the substitution can be a conservative substitution, and can include, for example, R81I, R81T, R81D, L85V, I86V, I89V, I92F or V93I (p. 12, lines 8-11)(bolded substitutions are those recited in present claim 3). Note also that claim 1 recites that X1 (which is position 81) can be substituted with any residue, so the R81T and R81D substitutions taught by Sahin also meet this limitation. Claim 1 further recites that X10 (which is position 92) is an uncharged residue, and the instant specification defines phenylalanine (F) as an uncharged residue (see p. 11 line 31). As such, the I92F substitution taught by Sahin is also on point to claim 1. Finally, Sahin teaches that the IL2 variant polypeptides bind to IL2Rbg with an affinity at least 10-fold greater than the affinity with which wild-type IL2 binds IL2Rbg (p. 37 lines 19-21). Accordingly, Sahin fully anticipates the IL2 polypeptide of instant claim 1.
Regarding claims 88 and 90, Sahin teaches that the IL2 variant may be fused to a heterologous polypeptide (i.e., a polypeptide that is not IL2), wherein the heterologous polypeptide can increase the circulating half-life of IL2, such as human serum albumin (HSA)(p. 35, lines 5-9; p. 38 line 28 – p.39 line 2). Sahin teaches that the IL2 variant can also be prepared as a fusion polypeptide with heterologous polypeptides such as an Fc domain or Fc fragment, transferrin, or HSA binders (p. 39 lines 8-10; p. 43 lines 29-31).
Regarding claims 93-94 and 96, Sahin teaches that in addition to HSA, transferrin, or an Fc domain, the heterologous polypeptide fused to the IL2 mutein can be an immunoglobulin fragment (p. 13 lines 5-6). The term immunoglobulin fragment is defined to include the antigen-binding portion or antigen-binding fragment of an antibody, such as Fab fragments (p. 54 line 29 – p. 55 line 1). Single chain antibodies (scFv) are also encompassed by the term antigen-binding fragment (p. 55 lines 11-12).
With respect to claim 100, Sahin discloses a polynucleotide encoding the IL2 variant polypeptide of the invention (p. 13 lines 18-19).
Regarding claim 101, Sahin teaches that an appropriate vector containing the polynucleotide may be used for transcription (i.e., an expression vector)(p. 31 lines 14-15).
Regarding claim 102, Sahin teaches a host cell comprising the polynucleotide encoding the IL2 variant polypeptide of the invention (p. 13 lines 21-22).
Regarding claim 104, Sahin discloses a pharmaceutical composition comprising the IL2 variant polypeptide (p. 13 lines 24-25), wherein the pharmaceutical composition further comprises one or more pharmaceutically acceptable carriers, diluents and/or excipients (p. 17 lines 4-6).
Regarding claims 105-109, Sahin teaches a method of treating a subject comprising administering to the subject the IL2 variant polypeptide of the invention, wherein the subject has cancer (p. 13 lines 28-32). The IL2 variant polypeptide is taught to activate effector T cells over regulator T cells (p. 5 lines 1-3). The therapeutic polypeptide is disclosed to be provided to the subject in a therapeutically effective amount (p. 26 lines 14-15). Sahin further teaches that the type of cancer to be treated can include carcinoma, lymphoma, blastoma, sarcoma, and leukemia, and more specifically: melanoma, lung cancer, breast cancer, renal cell carcinoma, pancreatic cancer, glioma (which term encompasses glioblastomas), or brain cancer, among others (p. 15 lines 24-26; p. 69 lines 1-12).
Claim Rejections - 35 USC § 103
The following is a quotation of 35 U.S.C. 103 which forms the basis for all obviousness rejections set forth in this Office action:
A patent for a claimed invention may not be obtained, notwithstanding that the claimed invention is not identically disclosed as set forth in section 102, if the differences between the claimed invention and the prior art are such that the claimed invention as a whole would have been obvious before the effective filing date of the claimed invention to a person having ordinary skill in the art to which the claimed invention pertains. Patentability shall not be negated by the manner in which the invention was made.
The factual inquiries for establishing a background for determining obviousness under 35 U.S.C. 103 are summarized as follows:
1. Determining the scope and contents of the prior art.
2. Ascertaining the differences between the prior art and the claims at issue.
3. Resolving the level of ordinary skill in the pertinent art.
4. Considering objective evidence present in the application indicating obviousness or nonobviousness.
13. Claim(s) 102-103 is/are rejected under 35 U.S.C. 103 as being unpatentable over Ma et al. (WO 2016/210293 A1) in view of Sahin et al. (WO 2020/020783 A1).
Ma et al. teach engineered cells comprising at least one chimeric antigen receptor (CAR) polypeptide (abstract; p. 3 lines 15-22), wherein the cells can include T cells or NK cells (p. 33 lines 8-19). Ma teaches that the engineered cells may also express an enhancer (a biological molecule that promotes or enhances the activity of the engineered cell having the CAR polypeptide), wherein the enhancer may be IL-2 (p. 41 line 20 – p. 42 line 10). Ma discloses that CD8+ T cells, for example, can be modified to express autocrine growth factors such as IL-2, IL-7, IL21 or IL-15, to sustain survival following transfer in vivo (p. 42 line 22 – p. 43 line 2).
Thus, Ma teaches a modified cell that expresses a CAR and IL2. However, Ma does not teach that the IL2 polypeptide that is expressed is an engineered IL2 polypeptide as in present claim 1.
The teachings of Sahin et al. are discussed above and provide for an IL2 mutein or variant comprising an engineered IL2Rb binding region motif as in present claim 1, which Sahin teaches has at least 10-fold great affinity for the b-subunit of IL2R than wild-type IL2. Sahin further teaches that administration of such IL2 variant RNA is a promising approach to boost the therapeutic efficacy of multiple T and NK cell-based (cancer) immunotherapies (p. 3 lines 13-15), and that treatment using the IL2 variants would favor activation of T cells such as CD8+ T cells over Tregs in the tumor microenvironment to provide anti-tumor efficacy (p. 4 lines 8-10).
Accordingly, it would have been obvious to one of ordinary skill in the art at the time of filing to have substituted the IL2 variant of Sahin for wild-type IL2 for expression within the engineered immune cell of Ma and thereby arrive at the presently claimed invention. The motivation to do so comes from Sahin, which teaches that the engineered IL2 variants can enhance the therapeutic efficacy of anti-tumor immunotherapies, such as the CAR-T cells and CAR-NK cells as taught in Ma. Given that the modification of immune cells to express chimeric antigen receptors as well as immune enhancers such as IL2 was already known and practiced in the art (as evidenced by Ma), the skilled artisan would have had a reasonable expectation that the expression of Sahin’s IL2 variants within the immune cells of Ma would have been successful. Therefore, the combination of prior art references renders obvious the presently claimed invention of claims 102-103.
Double Patenting
The nonstatutory double patenting rejection is based on a judicially created doctrine grounded in public policy (a policy reflected in the statute) so as to prevent the unjustified or improper timewise extension of the “right to exclude” granted by a patent and to prevent possible harassment by multiple assignees. A nonstatutory double patenting rejection is appropriate where the conflicting claims are not identical, but at least one examined application claim is not patentably distinct from the reference claim(s) because the examined application claim is either anticipated by, or would have been obvious over, the reference claim(s). See, e.g., In re Berg, 140 F.3d 1428, 46 USPQ2d 1226 (Fed. Cir. 1998); In re Goodman, 11 F.3d 1046, 29 USPQ2d 2010 (Fed. Cir. 1993); In re Longi, 759 F.2d 887, 225 USPQ 645 (Fed. Cir. 1985); In re Van Ornum, 686 F.2d 937, 214 USPQ 761 (CCPA 1982); In re Vogel, 422 F.2d 438, 164 USPQ 619 (CCPA 1970); In re Thorington, 418 F.2d 528, 163 USPQ 644 (CCPA 1969).
A timely filed terminal disclaimer in compliance with 37 CFR 1.321(c) or 1.321(d) may be used to overcome an actual or provisional rejection based on nonstatutory double patenting provided the reference application or patent either is shown to be commonly owned with the examined application, or claims an invention made as a result of activities undertaken within the scope of a joint research agreement. See MPEP § 717.02 for applications subject to examination under the first inventor to file provisions of the AIA as explained in MPEP § 2159. See MPEP § 2146 et seq. for applications not subject to examination under the first inventor to file provisions of the AIA . A terminal disclaimer must be signed in compliance with 37 CFR 1.321(b).
The filing of a terminal disclaimer by itself is not a complete reply to a nonstatutory double patenting (NSDP) rejection. A complete reply requires that the terminal disclaimer be accompanied by a reply requesting reconsideration of the prior Office action. Even where the NSDP rejection is provisional the reply must be complete. See MPEP § 804, subsection I.B.1. For a reply to a non-final Office action, see 37 CFR 1.111(a). For a reply to final Office action, see 37 CFR 1.113(c). A request for reconsideration while not provided for in 37 CFR 1.113(c) may be filed after final for consideration. See MPEP §§ 706.07(e) and 714.13.
The USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/patent/patents-forms. The actual filing date of the application in which the form is filed determines what form (e.g., PTO/SB/25, PTO/SB/26, PTO/AIA /25, or PTO/AIA /26) should be used. A web-based eTerminal Disclaimer may be filled out completely online using web-screens. An eTerminal Disclaimer that meets all requirements is auto-processed and approved immediately upon submission. For more information about eTerminal Disclaimers, refer to www.uspto.gov/patents/apply/applying-online/eterminal-disclaimer.
14. Claims 1, 3, 36, 54, 56, 82, 85, 87, 93-94, 96 and 100-109 are provisionally rejected on the ground of nonstatutory double patenting as being unpatentable over claims 27, 38-39, 79-82, 89 and 91 of copending Application No. 18/262,122 (reference application). Although the claims at issue are not identical, they are not patentably distinct from each other because in each case the claims encompass identical engineered IL-2 polypeptide sequences. In particular, the claims of the ‘122 co-pending application are directed to a bifunctional protein that comprises an antigen-binding site that binds to PD-L1 and the engineered IL-2 polypeptide of the instant claims. For example, SEQ ID NO: 124 of the ‘122 application (claim 39) is identical to the instant SEQ ID NO: 183 (in claim 85), and SEQ ID NO: 96 of the ‘122 application (claim 39) is identical to the instant SEQ ID NO: 2 (instant claim 36). Multiple other sequences are also identical between the instant and co-pending applications. The claims of the ‘122 application further recite polynucleotides encoding the bifunctional protein, vectors and host cells comprising same, a pharmaceutical composition comprising the bifunctional protein, a method of modulating an immune response comprising administering the bifunctional protein, and a method of treating cancer, such as breast cancer, pancreatic cancer, lung cancer, glioblastoma, renal cell carcinoma or melanoma.
Therefore, the co-pending ‘122 claims anticipate the engineered IL-2 polypeptide fusion polypeptide comprising an engineered IL-2 polypeptide of the instant invention. This is a provisional nonstatutory double patenting rejection because the patentably indistinct claims have not in fact been patented.
Conclusion
15. No claims are allowed.
16. Co-pending Appl. No. 18/864,369, contains claims directed to an engineered IL2 polypeptide comprising an engineered IL2 receptor b (IL2Rb) binding region motif 2 is noted to contain some of the same amino acid substitutions within the same region (residues 81-95 of hIL2; i.e., an IL2Rb binding region) as the present claims. However, claim 1 of the ‘369 application recites that the engineered IL2 polypeptide binds to IL2Rb at a reduced affinity compared to wild-type IL2, which is the opposite of what is presently claimed. Therefore, it is the examiner’s opinion that the scope of the IL2 polypeptide recited in the ‘369 claims is distinct from that of the present invention.
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.
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/KIMBERLY BALLARD/Primary Examiner, Art Unit 1675