DETAILED ACTION
The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
Status of the Application
Receipt is acknowledged of Applicants’ preliminary amendment, filed on 06/09/2023, in which claims 1-31 are canceled and claims 32-45 are newly added.
Claims 32-45 are pending and are examined on the merits herein.
Priority
The instant application is a 371 of PCT/GB2021/053182 filed on 12/06/2021, which claims foreign priority to UNITED KINGDOM 2019460.1 filed on 12/10/2020.
Information Disclosure Statement
The information disclosure statement (IDS) dated 06/09/2023 complies with the provisions of 37 CFR 1.97, 1.98 and MPEP § 609. Accordingly, the information disclosure statement has been considered by the examiner.
Claim Objections
Claims 35 and 41 objected to because of the following informalities: Claims 35 and 41 contain the obvious typographical error of lacking a period at the end of the claim. Appropriate correction is required.
Claim Rejections - 35 USC § 112(d)
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.
Claim 36 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. Claim 36 recites “wherein the patient is known to have autoimmune encephalitis” and depends from claim 32, which is limited to a patient diagnosed with autoimmune encephalitis. Thus claim 36 fails to further limit the claim from which it depends. 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.
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 32-33 and 36 are rejected under 35 U.S.C. 103 as being unpatentable over Freeman (Pediatric Neurology, 2005; PTO-892) in view of Varadkar et al. (The Lancet, 2014; IDS 06/09/2023).
Freeman discusses the state of the art in the pathology, diagnosis, and treatment of Rasmussen’s encephalitis (abstract). Freeman teaches that Rasmussen’s syndrome is now known to be a severe autoimmune process leading to destruction of a single hemisphere (page 298, paragraph 4). Freeman teaches that patients with Rasmussen’s syndrome may be treated by immunotherapy with steroids, plasmaphoresis, and intravenous immunoglobulin, which provide temporary relief to many, but patients always relapse (page 298, paragraph 3). For example, the seizures associated with Rasmussen’s syndrome are among the most intractable of all seizure types. While medications may at times result in temporary decrease in the seizures, patients inevitably become refractory. Medication only is thus but a temporizing measure (page 296, paragraph 2). Immuno-ablative therapy, in which the individual’s immune cells are wiped out with cyclophosphamide and the immune system is reconstituted by the patient’s own cyclophosphamide-resistant progenitor cells, has been used in two children with Rasmussen’s syndrome, with promising results (page 298, paragraph 3).
The teachings of Freeman differ from that of the instantly claimed invention in that Freeman does not teach administration of cladribine.
Varadkar discusses the characteristics and treatments of Rasmussen’s encephalitis. (abstract). Varadkar states that the search continues for immunological treatments that can halt both the seizures and the functional decline caused by Rasmussen’s encephalitis. Multiple sclerosis treatments are promising candidates (page 200, paragraph 3). Varadkar provides a list of candidate treatments for Rasmussen’s encephalitis, which includes cladribine as a treatment which disrupts lymphocyte cellular processes and can penetrate the CNS (Table on page 201).
It would have been prima obvious to combine the teachings of Freeman and Varadkar before the effective filing date of the claimed invention by treating the Rasmussen’s encephalitis patients of Freeman with the cladribine of Varadkar to arrive at the instantly claimed invention. It would have been prima facie obvious for one of ordinary skill in the art to treat Rasmussen’s encephalitis patients using cladribine because Varadkar teaches that cladribine is a candidate treatment for Rasmussen’s encephalitis. One of ordinary skill in the art would have a reasonable expectation of success because Freeman teaches that treatments disrupting the immune system have shown promising results and Varadkar teaches that cladribine disrupts lymphocyte cellular processes.
Claims 37-45 are rejected under 35 U.S.C. 103 as being unpatentable over Freeman (Pediatric Neurology, 2005; PTO-892) in view of Varadkar et al. (The Lancet, 2014; IDS 06/09/2023), as applied to claim 32, further in view of Costello et al. (Journal of Neuroscience Nursing, 2008; IDS 06/09/2023).
The combined teachings of Freeman and Varadkar teach the method of claim 32, as discussed in detail above.
The combined teachings of Freeman and Varadkar do not teach the dose form of the cladribine.
Costello discusses the formulation of cladribine in the treatment of MS (abstract). Costello teaches that cladribine targets both T and B lymphocytes (page 276, paragraph 1). Costello discloses an oral formulation of cladribine with improved safety profiles and improved routes of administration (abstract). Costello teaches that this formulation is in the form of a 10 mg tablet of oral cladribine. The number of tablets administered is standardized based on patient weight (page 278, paragraph 2). One treatment course with cladribine tablets is defined as once-daily therapy (page 278, paragraph 4). Costello teaches that oral formulations can be of great benefit to patients in terms of convenience, quality of life, and improved adherence (page 276, paragraph 1).
One of ordinary skill in the art would have been motivated to administer the cladribine in the method of Freeman and Varadkar in the form of the oral cladribine tablets taught by Costello because Costello teaches that oral formulations can be of great benefit to patients in terms of convenience, quality of life, and improved adherence. One of ordinary skill in the art would have had a reasonable expectation of success because Costello teaches that this formulation is used in the treatment of MS and Varadkar teaches that promising candidates for Rasmussen’s encephalitis come from multiple sclerosis treatments.
Claims 32, 34-35, 36, and 39 are rejected under 35 U.S.C. 103 as being unpatentable over Dale et al. (Developmental Medicine & Child Neurology, 2012; PTO-892) in view of Ceronie et al. (Journal of Neurology, 2018; PTO-892).
Dale discusses the pathology and treatment of N-methyl-D-aspartate receptor (NMDAR) encephalitis (abstract). Dale teaches NMDAR encephalitis is an autoimmune encephalitis defined by the presence of autoantibodies that bind to the NMDAR (abstract). The instant specification defines antibodies to the NMDA receptor as anti-brain antibodies (Specification page 5, paragraph 4). Cerebrospinal fluid immunophenotyping has demonstrated B-cell expansion in opsoclonus–myoclonus and neuromyelitis optica, and has been used to support the humoral autoimmune hypothesis, and the use of drugs that deplete B-cell populations such as rituximab (page 191, paragraph 3). In particular, Dale discloses a study of NMDAR encephalitis patients observed to have very significant B-cell expansion (page 192, paragraph 3), and teaches that these B-cells are CD19+ B-cells (page 192, paragraphs 1-2). Dale teaches that this finding supports the use of drugs, such as rituximab, that deplete B-cells in severe or refractory cases of NMDAR encephalitis (abstract).
The teachings of Dale differ from that of the instantly claimed invention in that Dale does not teach administration of cladribine.
Ceronie discloses the mechanism of action of oral cladribine (abstract). Ceronie teaches that immunophenotyping data demonstrated that effective doses of oral cladribine induced marked (80–85%) CD19+ B cell depletion (page 1200, paragraph 4). Cladribine therefore behaves as a chemical CD19-depleter (paragraph bridging pages page 1207-1208).
It would have been prima facie obvious to administer the oral cladribine of Ceronie to the NMDAR encephalitis patients of Dale before the effective filing date of the claimed invention to arrive at the instantly claimed invention because the NMDAR encephalitis patients of Dale demonstrated B-cell expansion of CD19+ B-cells, and Ceronie teaches that cladribine therefore behaves as a chemical CD19-depleter. One of ordinary skill in the art would have a reasonable expectation of success because Dale suggests that drugs that deplete B-cells should be used in severe or refractory cases of NMDAR encephalitis.
Conclusion
No claims are allowed.
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/S.G.S./Examiner, Art Unit 1693
/SCARLETT Y GOON/Supervisory Patent Examiner, Art Unit 1693