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 .
Priority
The present application is a national stage application of International Patent Application NO. PCT/CN2020/128652, filed on November 13, 2020, which claims priority to the Chinese Patent Application No. 2020111292757, filed with the China National Intellectual Property Administration (CNIPA) on October 21, 2020.
Examiner’s Note
During a telephone conversation with Applicant’s attorney Mr. Daniel H. Bliss, on 06/24/2026, the attorney was informed of an improper claim amendment filed on 08/10/2023, 08/25/2023 and 05/03/2024. In a follow-up call on 06/25/2026, the attorney kindly acknowledged the discrepancy and confirmed the amendment of claim set filed on 08/25/2023 and that should be examined.
Status of Claims
Claims 1-5, 11-14, and 17-22 are pending.
The amendment filed on August 25, 2023, amended claims 3, 4, 18, 19, 21, and 22.
Claims 1-5, 11-14, and 17-22 are currently examined on the merits herein.
Information Disclosure Statement
The information disclosure statement including foreign patent document filed 08/10/2023 and 08/14/2023 fails to comply with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609 because a copy of translated abstract of CN’967, CN’145, CN’753, CN’156, CN’080, and CN’063 have not been provided. The information disclosure statement requires a legible copy of each cited foreign patent document. Applicant is advised that the date of any re-submission of any item of information contained in this information disclosure statement or the submission of 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 statement, including all certification requirements for statements under 37 CFR 1.97(e). See MPEP § 609.05(a).
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.
Claims 5 and 20 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 5 and 20 recite the limitation “the amino acid sequence of HSA further comprises a natural sequence” in line 1-2. The claims are indefinite because it is unclear what composition “natural sequence” is referencing. A review of the instant specification shows that the instant specification recites the same as stated in the claim language, and not any additional specifics are provided. The claims remain indefinite.
Claims 5 and 20 recite the limitation “a sequence after amino acid substitution and variation” in line 2. There is insufficient antecedent basis for this limitation in the claims because there is not prior recitation of the limitation and it is unclear what the limitation is referencing. For the purpose of compact prosecution the limitation will be interpreted to refer to the human serum albumin (HSA) of claim 1; however, the rejection will remain of record unless it is overcome by persuasive arguments and/or amendment.
Claims 5 and 20 further recite the limitation “a fragment of HSA” in line 2. This limitation renders the scope of claims 5 and 20 indefinite as it is unclear whether the recombinant fusion protein comprising the amino acid sequence of human serum albumin (HAS) is open to a polypeptide of any length, as suggested by the use of the transitional phrase further comprising, or whether said polypeptide is limited to any particular amino acid length. For purposes of examination, the recombinant fusion peptide comprising HSA of claims 5 and 20 and all dependent claims is being interpreted as stated in the specification as HSA - GeneBank number AY728024.
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-AIA 35 U.S.C. 102 and 103) is incorrect, any correction of the statutory basis (i.e., changing from AIA to pre-AIA ) 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 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 1-5, 11, 14, and 17-20 are rejected under 35 U.S.C. 103 as being unpatentable over Sasaki et. al. (“Engineered collagen-binding serum albumin as a drug conjugate carrier for cancer therapy”; Koichi Sasaki, Jun Ishihara, Ako Ishihara, Risako Miura, Aslan Mansurov, Kazuto Fukunaga, Jeffrey A. Hubbell; Sci. Adv. 2019; 5 : eaaw6081, page 1-12, published August 14, 2019; cited in IDS filed August 10, 2023) in view of WO 2020176478 (published September 3, 2020) and further in view of EP 3318124 (published May 9, 2018).
Sasaki et. al. developed an approach to retain serum albumin-drug conjugates within tumors through a combination of passive and active targeting (see Abstract). Serum Albumin (SA) was recombinantly fused with a collagen-binding domain (CBD) of von Willebrand factor to bind within the tumor stroma after extravasation due to tumor vascular permeability (see Abstract). Doxorubicin (Dox) was conjugated to the CBD-SA via a pH-sensitive linker; and Dox-CBD-SA treatment significantly suppressed tumor growth (see Abstract).
Sasaki et. al. discloses design of recombinant mouse SA (CBD-SA) in which the N terminus is fused with the C terminus of the A3 domain of von Willebrand factor, and aldoxorubicin (i.e., chemotherapy drug) was conjugated to CBD-SA via a pH-dependent cleavable hydrazone linkage before injection (namely, Dox-CBD-SA) (see page 1, right col, paragraph 3). Sasaki et. al. further discloses serum albumin (SA) was expressed recombinantly with the collagen-binding domain (CBD) on the N terminus of mouse SA using a (GGGS)2 linker (see RESULTS, page 2, paragraph 1, and Amino acid sequence of CBD-SA in table S1).
Sasaki et. al. teaches CBD-SA is produced with high yield [human embryonic kidney 293 (HEK293)] cell culture; and also proposed preconjugation of Dox to CBD-SA produces high antitumor efficacy with a simple and translatable production method (see page 8, left col, paragraph 3). Sasaki et. al. discloses the sequences encoding for the fusion of human VWF A3 domain residues Cys1670-Gly1874 (907-1111 of mature VWF) and mouse SA without pro-peptide (25 to 608 amino acids of whole SA) were synthesized and subcloned into the mammalian expression vector (see page 8, right col, Production and purification of CBD-SA) {Similarly, the instant Specification states that Collagen-binding domain (CBD) is a part of the von Willebrand Factor (vWF) of human von Willebrand disease type A. vWF; this protein has multiple domains, among which the A3 domain mediates platelet aggregation; vWF-A3 domain (also known as CBD) refers to a peptide segment between 920 to 1111 of a mature peptide; instant Specification [0007] and [0008])}.
However, Sasaki et. al. is silent about ligating a human collagen-binding domain (CBD) to a C-terminal of a human serum albumin (HSA).
WO’478 discloses engineering of collagen-binding modification of anti-inflammatory agents using collagen-binding peptide (CBP) and vWF A3 to achieve targeted therapy for inflammatory diseases (see Abstract). WO’478 discloses in some embodiments, the anti-inflammatory agent operatively linked to an extracellular matrix (ECM)-affinity peptide further comprises a serum protein operatively linked to the peptide or agent. In some embodiments, the serum protein is operatively linked to the peptide. In some embodiments, the serum protein is operatively linked to the peptide through a peptide bond. In some embodiments, the serum protein comprises albumin (see [0014]). WO’478 specifies, in some embodiments, the serum protein is amino-proximal to the ECM-affinity peptide; in some embodiments, the serum protein is carboxy-proximal to the ECM-affinity peptide (see [0014]). WO’478 discloses the ECM-affinity peptides is further linked to a serum protein; serum proteins include, for example, albumin; the albumin may be mouse, human, bovine, or any other homologous albumin protein; and in some embodiments, the albumin comprises human serum albumin (see [0147]). As disclosed by WO’478, SEQ ID NO: 51 has 97.2% sequence match with the instant SEQ ID NO: 1 and SEQ ID NO: 65 has 97.5% sequence match with the instant SEQ ID NO: 3.
EP’124 teaches method for assessing one or more (several) pharmacokinetic properties of a variant human serum albumin (HSA) compared to wild type HSA. The pharmacokinetic properties of molecules where the Wt HSA and variant HSA is modified by fusion, conjugation or association with a partner such as therapeutic agents, vaccines or diagnostic agents are of particular interest (see [0010]). EP’124 elaborates the benefits of using albumin for drug delivery are longer half-life and/or controlled release of a therapeutic agent and/or targeting to selective tissues or organs (see [0005]). EP’124 summarizes the circulatory half-lives of wild-type (Wt) albumin in various animals (see Table 2) where the plasma half-life of wild type human serum albumin (HSA) has been found to be approximately 19 days vs mouse serum albumin has been found to be approximately 1.2 days (see [0035], Table 2).
It would have been obvious to combine the teachings of Sasaki et. al. and WO’478 along with EP’124 before the effective filing date of the claimed invention by engineering collagen-binding serum albumin as a drug conjugate carrier with extended half-life, as an effective cancer therapy. One of ordinary skill in the art would have been motivated to utilize the fusion of recombinant collagen binding domain and serum albumin along with conjugation of chemotherapeutic agents as taught by Sasaki et. al. as potent tumor-targeted drug carrier leading to improved antitumor efficacy by efficient Dox delivery to the tumor environment (see page 2, left col, paragraph 1). Thus, one skilled in the art can utilize the long circulatory half-life of human serum albumin (SA) as taught by EP’124 (see [0033]) modified along with collagen-binding peptide (CBP) as taught by WO’478 and Sasaki et. al. and thus provides broad applicability to various types of solid tumors as a drug carrier including potential for clinical translation to cancer therapy as an antitumor drug carrier (see Sasaki et. al. page 8, right col, paragraph 1).
Regarding claim 1: Sasaki et. al. teaches serum albumin (SA) was expressed recombinantly with the collagen-binding domain (CBD) on the N terminus of mouse SA using a (GGGS)2 linker (see RESULTS, page 2, paragraph 2). WO’478 discloses collagen-binding peptide (CBP) and vWF A3 to achieve targeted therapy (see [0004]) and the ECM-affinity peptides is further linked to a serum protein; serum proteins include, for example, albumin; the albumin may be mouse, human, bovine, or any other homologous albumin protein; and in some embodiments, the albumin comprises human serum albumin (see [0147]). As disclosed by WO’478, (i) SEQ ID NO: 51 has 97.2% sequence match with the instant SEQ ID NO: 1 which is equivalent to CBD-SA with human CBD ligated to the N-terminus of human SA and (ii) SEQ ID NO: 65 has 97.5% sequence match with the instant SEQ ID NO: 3 which is equivalent to SA-CBD with human CBD ligated to the C-terminus of human SA.
Regarding claims 2 and 17: WO’478 discloses the polypeptides or polynucleotides of the disclosure, such as the ECM-affinity peptide, serum protein, or cytokine polypeptide, may include 1, …. or 50 or more variant amino acids or nucleic acid substitutions or be at least 60%, … or 100% similar, identical, or homologous with at least, or at most 3, … 1000 or more contiguous amino acids or nucleic acids, or any range derivable therein, of SEQ ID NOs: 1-66 (for example SEQ ID NO: 51 is 97.2% identical with in SEQ ID NO: 1). This is in direct correlation with the instant specification which states, the amino acid sequence of HSA further includes a natural sequence, or a sequence after amino acid substitution and variation, or a fragment of HSA (see instant Specification [0022]).
Regarding claims 3 and 18: WO’478 discloses, SEQ ID NO: 65 has 97.5% sequence match with the instant SEQ ID NO: 3 which is equivalent to SA-CBD with human CBD ligated to the C-terminus of human SA including GGGS2 as linker.
Regarding claims 4 and 19: WO’478 further specifies linkers may have one or more properties that include a flexible conformation, an inability to form an ordered secondary structure or a hydrophobic or charged character which could promote or interact with either domain; examples of amino acids typically found in flexible protein regions may include Gly, Asn and Ser; for example, a suitable peptide linker may be GGGSGGGS or (GGGS)n wherein n = 1, 2, 3, 4, 5, 6, 7, 8, 9, or 10 (or any range derivable therein) (see [0016]). WO’478 teaches the recombinant polynucleotides encoding the proteins, polypeptides, and peptides of the invention, such as ECM-affinity peptide; certain embodiments relate to nucleotides encoding for an ECM-affinity polypeptide and/or an ECM-affinity polypeptide or fragment thereof (see [0172]). WO’478 specifies SEQ ID NO: 51 has 97.2% sequence match with the instant SEQ ID NO: 1 which is equivalent to CBD-SA with human CBD ligated to the N-terminus of human SA including GGGS2 as linker.
Regarding claims 5 and 20: WO’478 discloses serum proteins include, for example, albumin, globulin, and fibrinogen; globulins include alpha 1 globulins, alpha 2 globulins, beta globulins, and gamma globulins; the albumin may be mouse, human, bovine, or any other homologous albumin protein. In some embodiments, the albumin comprises human serum albumin, which is encoded by the ALB gene, and exemplified by the amino acid sequence SEQ ID NO: 45 and SEQ ID NO: 60 (see [0147]), SEQ ID NO: 51 (see [0150]); the polypeptides or polynucleotides of the disclosure, such as the ECM-affinity peptide, serum protein, or cytokine polypeptide, may include 1…..1000 or more contiguous amino acids or nucleic acids, or any range derivable therein, of SEQ ID NOs: 1-66 (see [0151]); or peptides, polypeptides, and proteins of the disclosure, such as the ECM-affinity peptide, serum protein, or cytokine polypeptide, having at least, having at least, or having 70, 75, 80, 85, 90, 91, 92, 93, 94, 95, 96, 97, 98, 99, 100% identity to any one of SEQ ID NO: 1-66 (see [016]).
Regarding claim 14: Sasaki et. al. teaches engineered CBD-SA could be a versatile and clinically relevant drug conjugate carrier protein for treatment of solid tumors (see Abstract). Sasaki et. al. also teaches CBD-SA acts independently of tumor type–specific antigens and thus provides broad applicability to various types of solid tumors as a drug carrier (see page 8, left col, paragraph 5 – right col, paragraph 1).
Regarding claims 11: Sasaki et. al. teaches serum albumin (SA) was recombinantly fused with a collagen-binding domain (CBD) of von Willebrand factor to bind within the tumor stroma (see Abstract). Dox is often used in combination with other chemotherapeutic agents (see page 1, right col, paragraph 2); aldoxorubicin was conjugated to CBD-SA (see page 1, right col, paragraph 3). Sasaki et. al. evaluated engineered CBD-SA as a tumor-targeted drug carrier, leading to improved antitumor efficacy by efficient Dox delivery to the tumor microenvironment (see page 2, left col, paragraph 1). Sasaki et. al. discloses Dox conjugates are taken up by cancer cells and retain cytotoxicity (see page 2, left col, paragraph 4). Sasaki et. al. teaches Dox conjugation to CBD-SA showed significantly higher accumulation of Dox within tumor tissue (see page 7, left col, paragraph 1), and Dox internalizes within cells via passive transmembrane diffusion and interferes with DNA functions, leading to death of proliferating cells (see page 1, right col, paragraph 2).
Although Sasaki et. al. does not provide many examples of other chemotherapy drugs that interferes with transcription of DNA or cytotoxic proteins that induce programmed cell death, however, Sasaki et. al. does elaborate with specific example of using Doxorubicin (Dox) to improve efficacy, Dox is often used in combination with other chemotherapeutic agents, and Dox has been reported to facilitate immune cell infiltration into tumors through induction of immunogenic cell death (see page 1, right col, paragraph 2). Sasaki et. al. further teaches Dox-CBD-SA efficiently stimulated host antitumor immunity, resulting in the complete eradication
of MC38 colon carcinoma when used in combination with anti–PD-1 checkpoint inhibitor (see Abstract). Thus, one skilled in the art would have been motivated to utilize the chemotherapeutic agents or cytotoxic protein as pharmaceutical composition conjugated with CBD-SA to serve as a versatile and clinically relevant drug conjugate carrier protein for treatment of solid tumors (Sasaki et. al. see Abstract). One of ordinary skill in the art would have been motivated to do so with an expectation to succeed in utilizing CBD-SA as tumor type–specific antigens and thus provide broad applicability to various types of solid tumors
as a drug carrier (Sasaki et. al. see page 8, right col, paragraph 1).
Therefore, the presently claimed invention was prima facie obvious to one of ordinary skill in the art at the time of the effective filing date.
Claims 12 and 21 are rejected under 35 U.S.C. 103 as being unpatentable over Sasaki et. al. (“Engineered collagen-binding serum albumin as a drug conjugate carrier for cancer therapy”; Koichi Sasaki, Jun Ishihara, Ako Ishihara, Risako Miura, Aslan Mansurov, Kazuto Fukunaga, Jeffrey A. Hubbell; Sci. Adv. 2019; 5 : eaaw6081, page 1-12, published August 14, 2019; cited in IDS filed August 10, 2023) and WO 2020176478 (published September 3, 2020), as previously applied to claims 1-5, 11-14, and 17-20; and further in view of Weber (“Molecular Therapies of Cancer”; Georg F. Weber; Springer International Publishing; ISBN 978-3-319-13278-5 (eBook), published 2015).
Weber teaches upon aquation of a ligand, platinum drugs become highly reactive, allowing them to coordinate DNA bases. Complexes with labile leaving groups are toxic, compounds with stable leaving groups are inactive. Modifications in the chloride leaving group affect pharmacokinetics; modifications in the ligand affect efficacy and spectrum of activity. Most platinum compounds cannot be taken orally. Early generation platinum drugs have severe adverse effects. Recent generation platinum drugs reduce toxicity and avoid cross-resistance. Drug resistance may be caused by platinum efflux, detoxification through thiols, apoptosis resistance, or enhanced DNA repair (see page 42-43, Emerging platinum drug derivatives, paragraph 5). Weber teaches that in platinum based combination therapy, a common approach is the combination of one or more non-platinum anti-cancer drugs with a platinum compound. Cisplatin, carboplatin, and oxaliplatin have been evaluated in combination with vinblastine, paclitaxel, doxorubicin, etc (see page 271, 7.2 Treatment of Solid Tumors -7.2.3 Platinum Based Chemotherapy, paragraph 2). Weber also teaches for de novo endocrine resistant (negative for Estrogen Receptor and Progesterone Receptor) metastatic breast cancer, chemotherapy is the most appropriate first-line treatment option; increasingly patients receive the most active agents, anthracyclines and taxanes, in the adjuvant setting (see page 329, right col paragraph 1). Weber further teaches intensive, multi-cyclic therapy with several drugs that have various mechanisms of action and dosing regimens includes DNA and RNA alkylation (cyclophosphamide), anti-folates (methotrexate), anti-purines and anti-pyrimidines (6-mercaptopurine, 6-thioguanine), incorporation into DNA or RNA (cytarabine), microtubule inhibition (vincristine), membrane stabilization (prednisone), and inhibition of Topoisomerase 1 (topotecan) and 2 (anthracycline) (see page 268, left col, paragraph 4). Weber adds nucleosome structure and DNA accessibility can be altered by several multi-protein remodeling complexes
or by the covalent post-translational modification (see page 272, left col, paragraph 1); and combination chemotherapy for cancer combines agents that uniformly exert DNA damage to
suppress cell division, thus predominantly reducing the adverse effects of high dose monotherapy (see Fig 7.1, page 278).
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e., applicants individual components in the composition of chemotherapy drug is selected from the group consisting of a platinum drug, an antifolate drug, an antipyrimidine drug, a vinblastine drug, a taxane drug, an anthracycline drug, a drug that disrupts structure and function of DNA, a drug that is intercalated into DNA and interferes with transcription of the DNA, and a drug that affects protein synthesis, etc. were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art. Therefore, it would have been obvious to one of ordinary skill in the art to make the instantly claimed pharmaceutical composition based on the recombinant fusion protein coupled with a chemotherapy drug with a reasonable expectation of succeed.
Claims 13 and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Sasaki et. al. (“Engineered collagen-binding serum albumin as a drug conjugate carrier for cancer therapy”; Koichi Sasaki, Jun Ishihara, Ako Ishihara, Risako Miura, Aslan Mansurov, Kazuto Fukunaga, Jeffrey A. Hubbell; Sci. Adv. 2019; 5 : eaaw6081, page 1-12, published August 14, 2019; cited in IDS filed August 10, 2023) and WO 2020176478 (published September 3, 2020), as previously applied to claims 1-5, 11-14, and 17-20; and further in view of Shapira et. al. (“Toxin-Based Therapeutic Approaches”; Assaf Shapira and Itai Benhar; Toxins 2010, 2, 2519-2583; published October 28, 2010).
Shapira et. al. provides a review of pharmaceutical potential of toxins used to impair essential cellular processes and/or damage the integrity of their target cells and summarizes the advances in the field of toxin based therapeutics and offers a comprehensive description of
the mode of action of each applied toxin (see Abstract). Shapira et. al. teaches that therapeutic agents composed of toxins conjugated to antibodies against cell surface antigens were shown to kill tumor cells; since then, many hybrid molecules consisting of a toxin coupled with a specific targeting antibody/ligand were developed; most of them are targeted against tumor cells (see Figure 1, page 2521, Ligand Targeted Toxins—Immunotoxins, paragraph 1). Shapira et. al. also discloses that although more specific, and better tolerated by animals, immunotoxins from the second generation were still chemically heterogeneous and their large size hindered them from penetrating solid tumors (see page 2521, Ligand Targeted Toxins—Immunotoxins, paragraph 2). Shapira et. al teaches the in vivo stability and cytotoxicity of diphtheria toxin-based polypeptides, artificially modified to initiate with short sequences derived from the FLAG peptide epitope differing only in their N-terminal amino acids, were assessed; and when the first N terminal amino acid of the modified toxins were Phe, Tyr, Trp, Asp, Asn, Glu, Gln, Lys, Arg or His, the proteins were highly unstable, with half-lives in the range 0.2–1.6 hours, while the toxins initiated with either of the remaining amino acids were considerably more stable, with half-lives ranging from 3 to >12 hours (see page 2545, paragraph 2). Shapira et. al. elaborates in the review regarding mechanism of action of cytotoxic agents ricin, diphtheria toxin, human chorionic gonadotropin (see Table 1, page 2523), deoxyribonuclease activity (see Figure 5), Pseudomonas Exotoxin A (see 2.2. Pseudomonas Exotoxin A Based Immunotoxins, page 2528-2531), etc. Shapira et. al. further teaches cytotoxic polypeptide in which human epidermal growth factor (EGF) and interleukin-4 (IL-4) are linked to the B-cell epitopes-deleted PE38, and when administrated to a mouse model of metastatic breast carcinoma, immunogenicity was reduced by about 90% (in comparison to the non-mutated construct) with no apparent loss of anti-tumor activity (see page 2547, paragraph 2; Table 1). Thus review by Shapira et. al. provides highlights of several studies evaluated clinically, or are currently undergoing clinical evaluation, mostly in context of oncological diseases (see page 2521, paragraph 1).
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e., applicants individual components in the composition of cytotoxic protein is selected from the group consisting of ricin, diphtheria toxin, Pseudomonas aeruginosa exotoxin, an inhibitor of apoptosis protein, human epidermal growth factor, gonadotropin-releasing hormone, and deoxyribonuclease II, etc. were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art. Therefore, it would have been obvious to one of ordinary skill in the art to make the instantly claimed pharmaceutical composition based on the recombinant fusion protein coupled with a cytotoxic protein with a reasonable expectation of succeed.
Therefore, the presently claimed invention was prima facie obvious to one of ordinary skill in the art at the time of the effective filing date.
Conclusion
No claim is allowed.
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/KOYELI BANERJEE/Examiner, Art Unit 1658
/Melissa L Fisher/Supervisory Patent Examiner, Art Unit 1658
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