DETAILED ACTION
Notice of Pre-AlA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 12, 2025, has been entered.
Claim Disposition
3. Claims 5-13, 20-21 and 30-47 have been cancelled. Claims 1-4, 14-19 and 21-29 are pending and are under examination.
Claim Objection
4. Claims 1-4, 14-19 and 21-29 are objected to for the following informalities:
For clarity and precision of claim language it is suggested that claim 1 is amended to read, “A method of treating colon cancer in a patient [[in need thereof]], comprising:
Intravenously……”. The dependent claims hereto are also included.
For clarity it is suggested that claim 2 is amended to read, “The method of claim 1, wherein the protein [[has 100% sequence identity]] is set forth in SEQ ID NO:1”.
Duplicate Claims, Warning
5. Applicant is advised that should claim 1 be found allowable, claims 2-3 will be objected to under 37 CFR 1.75 as being a substantial duplicate thereof. When two claims in an application are duplicates or else are so close in content that they both cover the same thing, despite a slight difference in wording, it is proper after allowing one claim to object to the other as being a substantial duplicate of the allowed claim. See MPEP § 706.03(k).
Correction of the above is required.
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.
6. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
7. Claim(s) 1-4, 14-19 and 21-20 is/are rejected under 35 U.S.C. 103 as being unpatentable over Abribat (US2012/0100121, cited on the IDS) in view of El-Ahmady El-Naggar et al. (Scientific Reports, 2016) and Chang et al. (cited on IDS 11/30/23).
Abribat teaches a method of treating a disease treatable by L-asparagine depletion in a patient (see paragraph [0123],"The conjugates of the invention can be used in the treatment of a disease treatable by depletion of asparagine. For example, the conjugate is useful in the treatment or the manufacture of a medicament for use in the treatment of acute lymphoblastic leukemia (ALL), in both adults and children comprising administering an effective amount conjugate paragraph[0022],"administering an effective amount of the conjugate of the invention") of a protein having substantial L- asparagine aminohydrolase activity and polyethyleneglycol (PEG), wherein the Polyethylene glycol has a molecular weight less than or equal to about 5000Da, wherein the protein is a L-asparaginase from Erwinia (see abstract "a protein having substantial L-asparagine amino hydrolase activity and polyethyleneglycol. In particular, the polyethyleneglycol has a molecular weight less than or equal to about 5000 Da and the protein is an L-asparaginase from Erwinia.";[0149],"Erwinase (R)isa commercially available crisantaspase (L-asparaginase derived from Erwinia chrysanthemi)" [0174],"As shown in FIG.11,the production of anti-conjugate antibodies remained of low intensity and frequency for the 2kDa and 5kDa mPEG-r-crisantaspase conjugates"). Abribat teach a structure that matches SEQ ID NO:1 with percentages as well as the full-length which makes obvious claim 2 and claim 3 since the Erwinia derived
enzyme is taught (see paragraph [0054]). Abribat also teach the PEG has a molecular weight of about 5000 Da, 4000 Da, 3000 Da, 2500 Da or 2000 Da (see abstract, FIG 11, and paragraph[0174]). At paragraph [0019], Abribat discloses that, the PEG is covalently linked to one or more amino groups (wherein "amino groups" includes lysine residues and/or the N-terminus) of the L-asparaginase. In a more specific embodiment, the PEG is covalently linked to the one or more amino groups by an amide bond. In another specific embodiment, the PEG is covalently linked to at least from about 40% to about 100% of the accessible amino groups (e.g., lysine residues and/or the N-terminus of the protein) or at least from about 40% to about 90% of total amino groups (e.g., lysine residues and/or the N-terminus of the protein). In one embodiment, the conjugate has the formula:
Asp-[NH--CO--(CH2)x-CO--NH-PEG]n
wherein Asp is the L-asparaginase, NH is one or more of the NH groups of the lysine residues and/or the N-terminus of the Asp, PEG is a polyethylene glycol moiety, n is a number that represents at least about 40% to about 100% of the accessible amino groups (e.g., lysine residues and/or the N-terminus) in the Asp, and x is an integer ranging from about 1 to about 8, more specifically, from about 2 to about 5. In a specific embodiment, the PEG is monomethoxy-polyethylene glycol (mPEG). Administration of the conjugate is disclosed by Arbitat at paragraph [0022], wherein it is stated that, the invention is directed to a method of treating a disease treatable by L-asparagine depletion in a patient comprising administering an effective amount of the conjugate of the invention. In one embodiment, the disease is a cancer. In a specific embodiment, the cancer is ALL. In another specific embodiment, the conjugate is administered at an amount of about 5 U/kg body weight to about 50 U/kg body weight. In another specific embodiment, the conjugate is administered at a dose ranging from about 10,000 to about 15,000 IU/m.sup.2 (about 20-30 mg protein/m.sup.2). In some embodiments, the administration may be intravenous or intramuscular and may be less than once per week (e.g., once per month or once every other week), once per week, twice per week, or three times per week. In other specific embodiments, the conjugate is administered as monotherapy and, more specifically, without an asparagine synthetase inhibitor. In other embodiments, the conjugate is administered as part of a combination therapy (but in some embodiments, the combination therapy does not comprise an asparagine synthetase inhibitor). In a specific embodiment, the patient receiving treatment has had a previous hypersensitivity to an E. coli asparaginase or PEGylated form thereof or to an Erwinia asparaginase. In another specific embodiment, the patient receiving treatment has had a disease relapse, in particular a relapse that occurs after treatment with an E. coli asparaginase or PEGylated form thereof. Further, Arbitat discloses at paragraph [0125], that the invention is directed to a method for treating acute lymphoblastic leukemia comprising administering to a patient in need of the treatment a therapeutically effective amount of a conjugate of the invention. In a specific embodiment, treatment will be administered at a dose ranging from about 1500 IU/m.sup.2 to about 15,000 IU/m.sup.2, typically about 10,000 to about 15,000 IU/m.sup.2 (about 20-30 mg protein/m.sup.2), at a schedule ranging from about twice a week to about once a month, typically once per week or once every other week, as a single agent (e.g., monotherapy) or as part of a combination of chemotherapy drugs, including, but not limited to glucocorticoids, corticosteroids, anticancer compounds or other agents, including, but not limited to methotrexate, dexamethasone, prednisone, prednisolone, vincristine, cyclophosphamide, and anthracycline. The claimed method of treatment has a single method step of administration, and although Arbitat does not per se mention colon cancer, the administration of the same protein conjugate would necessarily treat cancer in the patient’s body. Furthermore, El-Ahmady El-Naggar et al. teach that L-asparaginase can be used to treat colon cancer cells (see page1 and page 12). Further, Chang et al. teaches mutations in genes such as KRAS and found that the mutations were found higher in tumors and related to patient outcome, namely patient survival for treatment of colorectal cancer (see abstract, and pages 2-3). Based on the combined teaching rendering the claimed invention as obvious with respect to the conjugate, claims reciting resulting effects would also be deemed obvious such as the conjugate having a longer half-life. In addition, the combined teaching in the art of the activity of the L-asparaginase known in the art to deplete asparagine to affect the growth of the cancer cells renders the claimed invention obvious.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed invention as a whole because administration of L-asparaginase pegylated is known in the art as demonstrated by the primary reference to treat cancer. Albeit, the art is treating ALL, however, the claimed invention has a single method step of ‘administration’, thus the administration of the conjugate in the art would necessarily treat the cancer claimed, absent evidence to the contrary. In addition, the primary reference discloses the L-asparaginase as an anti-colon cancer protein as established in the secondary reference. Therefore, the claimed invention of treating colon cancer is obvious based on the disclosure in Chang et al. One of ordinary skill in the art would be motivated to combine the references as they are analogous art both teaching cancer treatment with the same protein.
Moreover, the Supreme Court pointed out in KSR, “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR, 127 S. Ct. at 1741. The Court thus reasoned that the analysis under 35 U.S.C. 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the “inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 1741. The Court further advised that “[a] person of ordinary skill is…a person of ordinary creativity, not an automation.” Id. at 1742. Therefore, the claimed invention was obvious to make and use at the time the invention was made and was prima facie obvious.
Response to Arguments
8. Applicant’s comments have been considered in full. Withdrawn objections/rejections will not be discussed herein as applicant’s comments are moot. Note that the rejections under 103 remains for the reasons stated above and herein (and the rejections have been amended to reflect changes made to the claims).
Note the 103 rejection remains and has been modified for the reasons stated above. Applicant traverses the rejection by stating that ALL is different from colon cancer and so is the treatment and that simply administering of the same protein conjugate to an ALL patient would not necessarily treat colon cancer in the patient in need. This argument is not persuasive when the instantly claimed method has one method step which is administration of the conjugate, with no dosage or treatment regimen (see claim 1). Although the claim has been amended to recite colon cancer the secondary reference by El-Ahmady E.-Naggar et al. teaches that L-asparaginase can be used to treat colon cancer, thus was known in the art. Claim 1 is very broad and is obvious over the combined teaching in the art. A patient with presentation of ALL and colon cancer would absolutely be treated with the simply administration intravenously of the conjugate. In addition, applicant separately attacks the references, however, the combined teaching renders the claimed invention as obvious. Applicant also argues limitations that are no longer present in the instant claims such as the effects of sensitivity to L-asparaginase. Furthermore, treatment does not equate to cure and the cited references in combinations meets the burden of treatment. The 103 statute requires a mere teaching or suggestions and as previously stated the KSR reasoning is appropriately applied and the motivation to combine is established, and the references are analogous art. The claim language also remains broad. The art teaches KRAS for instance which like NRAS is part of the RAS family (also included is HRAS gene). An ordinary skilled worker in the field would be able to understand that these are functionally equivalent (and the claims have been amended to recite a limitation not supported by the instant disclosure). Furthermore, In KSR v Teleflex (500 US 398 2007) (pages 12-13) " ... the Court has held that a "when a work is available in one field of endeavor, design incentives and other market forces can prompt variations of it, either in the same field or a different one (emphasis added). If a person of ordinary skill can implement a predictable variation, § 103 likely bars its patentability. For the same reason, if a technique has been used to improve one device, and a person of ordinary skill in the art would recognize that it would improve similar devices in the same way,using the technique is obvious unless its actual application is beyond his or her skill."
Thus, for all these reasons herein and above the rejections remain.
Conclusion
9. No claims are presently allowable.
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/HOPE A ROBINSON/Primary Examiner, Art Unit 1652