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 .
DETAILED ACTION
Status of Application/Amendment/Claims
The Finality of the Office Action mailed 11/05/2025 has been withdrawn.
Applicant's response filed 12/19/2025 has been considered. Rejections and/or objections not reiterated from the previous office action mailed 11/05/2025 are hereby withdrawn. The following rejections and/or objections are either newly applied or are reiterated and are the only rejections and/or objections presently applied to the instant application. The text of those sections of Title 35, U.S. Code not included in this action can be found in a prior Office action. Arguments to withdrawn rejections will not be addressed.
With entry of the amendment filed 12/19/2025 claims 1, 23, 28, 30, 33, 40-44 and 80-104 are pending.
New Claim Rejections
Claim Rejections - 35 USC § 112
The following is a quotation 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 35 U.S.C. 112 (pre-AIA ), first paragraph:
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.
Written Description
Claims 1, 23, 28, 30, 33, 40-44 and 80-104 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 pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
The MPEP states that the purpose of the written description requirement is to ensure that the inventor had possession, as of the filing date of the application, of the specific subject matter later claimed by him. The courts have stated:
To fulfill the written description requirement, a patent specification must describe an invention and do so in sufficient detail that one skilled in the art can clearly conclude that "the inventor invented the claimed invention." Lockwood v. American Airlines, Inc., 107 F.3d 1565, 1572, 41 USPQ2d 1961, 1966 (Fed. Cir. 1997); In re Gostelli, 872 F.2d 1008, 1012, 10 USPQ2d 1614, 1618 (Fed. Cir. 1989) ("[T]he description must clearly allow persons of ordinary skill in the art to recognize that [the inventor] invented what is claimed."). Thus an applicant complies with the written description requirement "by describing the invention, with all its claimed limitations, not that which makes it obvious" and by using "such descriptive means as words, structures, figures, diagrams, formulas, etc., that set forth the claimed invention." Lockwood, 107 F.3d at 1572, 41 USPQ2d at 1966; Regents of the University of California v. Eli Lilly & Co., 43 USPQ2d 1398.
The fundamental factual inquiry is whether the specification conveys with reasonable clarity to those skilled in the art that, as of the filing date sought, applicant was in possession of the invention as now claimed. See, e.g., Vas-Cath, Inc., 935 F.2d at 1563-64, 19 USPQ2d at 1117.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of the application. These include: (1) Actual reduction to practice, (2) Disclosure of drawings or structural chemical formulas, (3) Sufficient relevant identifying characteristics (such as: i. Complete structure, ii. Partial Structure, iii. Physical and/or chemical properties, iv. Functional characteristics when coupled with a known or disclosed structure, and v. Correlation between function and structure), (4) Method of making the claimed invention, (5) Level of skill and knowledge in the art, and (6) Predictability in the art.
Moreover, the written description requirement for a genus may be satisfied through sufficient description of a representative number of species by “…disclosure of relevant, identifying characteristics, i.e., structure or other physical and/or chemical properties, by functional characteristics coupled with a known or disclosed correlation between functional and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the claimed genus.” Thus when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus.
The claims are drawn to a genus of peptides and proteins comprising an epitope for inducing an immune response against an antigen in a subject. The instant specification defines a peptide as substances comprising 2 to about 150 consecutive amino acids and defines proteins as usually having greater than 151 amino acids (0175) and can include therapeutically active fragments and variants (0176). The specification describes a peptide or protein comprising an epitope that can be a viral, bacterial, tumor or any disease-associated antigen (0246-0251). Given the diversity of the genus of peptides, proteins, fragments of and variants of, this encompasses a vast number of different amino acid sequences.
The specification describe the genus of RNA encoding a peptide or protein comprising an epitope for inducing an immune response comprising an RNA encoding extended IL-2 and IL-L attached to an albumin. The specification and claims do not indicate what distinguishing characteristics of the peptide or proteins described in the specification that are concisely shared by the members of the broad genus that would convey to one of skill in the art that these dsRNA represent the entire genus. A review of the specification shows that it provides no description or guidance that would allow one of skill to distinguish the functional species of the recited structural genus from the non-functional members without empirical determination.
The prior art of Kang et al. ("Antimicrobial and immunomodulatory properties and applications of marine-derived proteins and peptides." Marine Drugs 17.6 (2019): 350) describes different antimicrobial immune modulating peptides and proteins wherein they can be derived from synthetic amino acids sequences or natural such as from marine life (see abstract). Kang et al. lists immunomodulatory peptides and proteins in Tables 2 and 4. The reference of Kang et al. highlights the vast genus of peptides and proteins capable of inducing an immune response from even a single type such as microbial.
Since the disclosure and the prior art fail to describe the common attributes and characteristics concisely identifying members of the proposed genus, and because the claimed genus is highly variant comprising an enormous amount of different amino acid sequences, fragments or variants with the function of inducing an immune response, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus claimed.
"A sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can "visualize or recognize" the members of the genus" (AbbVie, 759 F.3d at 1297, reiterating Eli Lilly, 119 F.3d at 1568-69) (emphasis added).
Further, “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” Ex parte Kubin, 83 USPQ2d 1410, 1417 (Bd. Pat. App. & Int. 2007) citing University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states that “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116).
The MPEP further states that if a biomolecule is described only by a functional characteristic, without any disclosed correlation between function and structure of the sequence, it is “not sufficient characteristic for written description purposes, even when accompanied by a method of obtaining the claimed sequence.” MPEP 2163. The MPEP does state that for generic claim the genus can be adequately described if the disclosure presents a sufficient number of representative species that encompass the genus. MPEP 2163. If the genus has a substantial variance, the disclosure must describe a sufficient variety of species to reflect the variation within that genus. See MPEP 2163. Although the MPEP does not define what constitute a sufficient number of representative, the Courts have indicated what do not constitute a representative number species to adequately describe a broad generic. In Gosteli, the Court determined that the disclosure of two chemical compounds within a subgenus did not describe that subgenus. In re Gosteli, 872 F.2d at 1012, 10 USPQ2d at 1618.
Thus the specification and claims lack written description because it is clear that Applicant did not have possession of every peptide or protein comprising an epitope for inducing an immune response. The description requirement of the patent statute requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736 F.2d 1516, 1521,222 USPQ 369,372-372 (Fed. Cir. 1984) (affirming rejection because the specification does "little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.").
Accordingly, it is deemed that the specification fails to provide adequate written description for the genus of the claims and does not reasonably convey to one skilled in the relevant art that the inventors, at the time the application was filed, had possession of the entire scope of the claimed invention.
Claim Rejections - 35 USC § 103
In the event the determination of the status of the application as subject to AIA 35 U.S.C. 102 and 103 (or as subject to pre-AlA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis for the rejection will not be considered a new ground of rejection if the prior art relied upon, and the rationale supporting the rejection, would be the same under either status.
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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
Claims 1, 23, 28, 30, 33, 40-44 and 80-104 is/are rejected under 35 U.S.C. 103 as being unpatentable over Wittrup et al. (WO 2016025642 of record cited on IDS 05/11/2023) (hereinafter Wittrup WO), Wittrup et al. (US Application 20150017120 cited on IDS 02/05/2025) (hereinafter Wittrup et al.), Zhu et al. (Cancer cell 2015 pg 489-501), Ballance et al. (US Patent 5,766,883 cited on IDS 02/05/2025), Gilles et al. (US Patent No. 7,589,179 cited on IDS 02/05/2025), Song et al. ("In vivo antitumor activity of a recombinant IL7/IL15 hybrid cytokine in mice." Molecular Cancer Therapeutics 15.10 (2016): 2413-2421) and Kreiter et al.(Current Opinion in Immunology 2011, 23:399-406 cited on IDS filed 07/30/2020).
Regarding claims 1, 23, 28, 81, 91, 95, Wittrup WO teach a medical preparation of an extended half-life IL-2 and a tumor specific antigen as a viable treatment for tumors (see page 1 first para under Background). Wittrup WO teach the prolonged circulation half-life of extended-PK IL-2 permits in vivo serum IL-2 concentrations to be maintained within a therapeutic range, leading to the enhanced activation of many types of immune cells, including T cells (see page 27 1st full para.). Wittrup WO teach nucleic acids such as RNA can be used to encode the IL-2 (see page 30 section a).
Regarding claims 80, 91 and 94, Wittrup WO teach the groups that are used to increase the circulation half-life are proteins or peptides such as human serum albumin, Fc or Fc fragments, PEG or transferrin that are linked to the end of the IL-2 (see page 12 second para. and pages 32-38).
Regarding claims 30, 33, 92 and 93, Wittrup WO additionally teach immune checkpoint blockers can be used in combination with the extended half-life IL-2 and a tumor specific antigen wherein the immune checkpoint blocker is an antibody that targets PD-1. PD-L1 or CTLA-4 (see page 50).
Regarding claims 40-44, Wittrup WO further teach using other therapeutic agents including antibodies or therapeutic proteins (page 55) along with teaching pharmaceutical compositions comprising acceptable carriers or diluents (see page 59).
Wittrup WO teach the pharmaceutical composition can be in a solution, solid, dehydrated or lyophilized powder (see page 64 3" para.). Wittrup WO do not teach using IL-7 in the medical preparation or teach sequences of IL-2 or IL-7 or the amino acid sequence of human serum albumin.
Regarding claims 23, 82-90 and 96-104 having the limitations of albumin sequences, IL2 and IL-7 sequences, Gillies et al. teach human IL-7 having SEQ ID No. 37 which is identical to instantly claimed SEQ ID No. 2. Gillies et al. teach IL-7 can comprise an immunoglobulin moiety (see col. 2, lines 14-21). Gilles et al. teach cytokines like IL-2 and IL-7 can be used to treat cancer and IL-7 is known to promote survival and proliferation of T-cells (see col. 1, lines 32-40) (see alignment at the end of this office action).
Wittrup et al. teach administering a therapeutic antibody and IL-7, which is important for generation and survival of memory T cells, along with the extended IL-2 in a pharmaceutical composition for use in treatments for cancer (see [0306], [0309]) and teach the IL-2 is human ([0085]. Wittrup et al. teach IL-2 sequences having SEQ ID No. 32 which is identical to instant SEQ ID No. 1.
Ballance et al. teach the well-known amino acid sequence of human serum albumin in SEQ ID No. 14 which is identical to the instantly claimed SEQ ID No. 5. (see alignment at the end of this office action).
Zhu et al. teach a fusion protein comprising IL-2 and an immunoglobulin Fc that extended the circulation half-life in vivo (see page 490 bottom col. 1-col.2). Zhu et al. teach the IL-2/Fc fusion protein had a synergistic immune effect in cancer cells when combined with another immunostimulatory agent as compared to IL-2/Fc fusion protein alone (see Results page 490 second col.). Zhu et al. teach the IL2/Fc combined with an immunostimulatory agent promotes CD8+ T cell activation (see page 495).
The prior art of Song et al. teach using a combination of two cytokines IL7 and IL15 with an increased in vivo half-life can induce an anti-tumor effect, such as increased CD4 and CD8+ that is greater than either cytokine alone (see Discussion pages 2419 and ). This provides evidence that using multiple cytokines together provides a synergistic anti-tumor effect.
It would have been obvious to try using the RNA encoding extended IL-2 attached to albumin along with a tumor specific antigen, as taught by Wittrup WO and combine with an RNA encoding extended IL-7 attached to an albumin for use in methods of inducing an immune response. It would have been obvious to make an IL-7 attached to albumin to extend the half like given Wittrup WO teach IL-2 half-life was extended using albumin and given Wittrup et al. teach IL-7 is important for generation and survival of memory T cells. It would have been obvious to try using the combination of RNA encoding extended IL-2/albumin and IL-7/albumin together given Gilles et al. teach cytokines like IL-2 and IL-7 can be used to treat cancer and IL-7 is known to promote survival and proliferation of T-cells and Wittrup et al. teach administering a therapeutic antibody and IL-7 along with the extended IL-2 in a pharmaceutical composition for use in treatments for cancer.
Moreover, it would have further been obvious to try and make the claimed agent to use in methods of enhancing immune responses in cancers such as melanoma given Lombardi et al. teach molecular engineering of cytokines with prolonged half-life enhanced specificity or localized activity is therefore required to enhance the pharmacological properties of these proteins (see 433-434) and teach in Table 1, IL-7 as well as IL-2 are known cytokines approved for clinical use in cancer treatments. One of skill in the art would have expected a synergistic effect given Zhu et al. demonstrates extended IL-2 along with an additional immunostimulatory molecule had a synergistic effect in melanoma cancer in vivo.
With respect to the limitation of a RNA encoding a peptide or protein, Kreiter et al. teach the use of antigen encoded mRNA to elicit an immune response in a subject (see page 401, column 1) and teach it is well known and safe to use mRNA-based immunotherapeutic strategies (see page 404 col. 1). Because Kreiter et al. teach the emergence and efficiency of mRNA as drug vehicles for induction of immune response against cancer, one of skill would have been motivated to construct the medical preparation as claimed.
Because there is a design need to make an agent capable of eliciting immune responses, such as against tumor cells and because there was a finite number of cytokines discussed above that have proven to be capable of eliciting an immune response, a person of ordinary skill in the art has good reason to pursue known options within their technical grasp. Furthermore, given it has been shown in the art that using a combination of cytokines together to elicit an immune response results in a synergistic immune response effect than when compared to individual cytokine treatments, there is an expectation of an advantage and thus a motivation to combine the prior art references for treatment of fibrosis (see MPEP 2144). Conclusive proof of efficacy is not required to show a reasonable expectation of success and obviousness does not require absolute predictability, but at least some degree of predictability is required (MPEP 2143.02).
Thus in the absence of evidence to the contrary, the invention as a whole would have been prima facie obvious to one of ordinary skill in the art at the time the invention was filed.
Response to Applicant’s argument
Applicant argues Wittrup WO does not teach an RNA encoding extended IL-2. Wittrup WO teach nucleic acids such as RNA can be used to encode the IL-2 (see page 30 section a). Thus it would have been obvious to use an RNA to encode the extended IL-2 and IL-7.
Applicant argues Wittrup WO does not teach a pharmaceutical composition. Wittrup WO teach the extended IL-2 and an immunomodulatory agent can be in pharmaceutical composition that can be in a solution, solid, dehydrated or lyophilized powder (see page 64). Thus it would have been obvious to use a pharmaceutical composition comprising the extended cytokines IL-2 and IL-7.
Applicant argues the Examiner mistakenly conflates data presented in Zhu et al. with data provided in the instant application. Zhu et al. was relied upon for teaching a combination therapy of extended IL-2 and a second immunostimulatory molecule provided a synergistic effect and thus the results of combining an extended IL-2 and IL-7 would be expected to produce a synergistic result as described in the 103 rejection above. Moreover, Zhu et al. and newly cited reference of Song et al. teach the combination agents induced an immune response such as increased CD8+ responses. Zhu et al. was never cited for the teaching the claimed data, but was cited in combination with the rest of the prior art cited to negate Applicant’s assertion of unexpected results.
Maintained Rejections
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. See 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);and, 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 a nonstatutory double patenting ground provided the reference application or patent either is shown to be commonly owned with this 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 §§ 706.02(l)(1) - 706.02(l)(3) 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 USPTO Internet website contains terminal disclaimer forms which may be used. Please visit www.uspto.gov/forms/. The 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 http://www.uspto.gov/patents/process/file/efs/guidance/eTD-info-I.jsp.
Claims 1-3, 6, 8-13, 16, 21-23, 28 and 80-84 are provisionally rejected under the judicially created doctrine of double patenting over claims 1-6 and 37 of co-pending Application No. 18,268,124 App ‘124). This is a provisional double patenting rejection since the conflicting claims have not yet been patented. Although the conflicting claims are not identical, they are not patentably distinct from each other because the instant claims and the claims of the patent are drawn to patently indistinguishable subject matter.
Both the instant claims and App ‘124 are drawn to a medical preparation comprising an RNA encoding a human IL-2 and IL-7 comprising human serum albumin. App ‘124 do not teach the medical preparation has an RNA encoding a peptide or protein. Kreiter et al. (cited above) teach the use of antigen encoded mRNA to elicit an immune response in a subject (see page 401, column 1) and teach it is well known and safe to use mRNA-based immunotherapeutic strategies (see page 404 col. 1).
It would have been obvious to combine the IL-2 and IL-7 comprising albumin with an antigen encoding mRNA as taught by Kreiter et al. to make a medical preparation for treating cancer. It would have further been obvious to use the instantly claimed medical preparation in the methods of treating cancer of Application ‘124 given it was taught in the art that this composition is useful for eliciting an immune response for treatment in cancer. The Court of Appeals for the Federal Circuit in Pfizer Inc, v Teva pharmaceuticals USA Inc., 86 USPQ2d 1001 at page 1008 (March 2008), indicated that there is no patentable distinction between claims to a product and a method of using that product disclosed in the specification of the application. Thus, the co-pending product could be used in the method of the instant claims.
This is a provisional obviousness-type double patenting rejection.
Re: Double Patenting
Acknowledgement is made of Applicant's argument that the application is a later filed application and should be withdrawn. If the instant application is determined to be allowed, then the later filed application will be withdrawn.
Conclusion
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/KIMBERLY CHONG/
Primary Examiner Art Unit 1636