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 .
Claims Status
Claims 1-18, 20, and 22 are pending and are examined on the merits.
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.
Claim 3 is 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 is rejected for making reference to Tables within the specification. Where possible, claims are to be complete in themselves. Incorporation by reference to a specific figure or table “is permitted only in exceptional circumstances where there is no practical way to define the invention in words and where it is more concise to incorporate by reference than duplicating a drawing or table into the claim.” See MPEP 2173.05(s).
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 2 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 2 depends from Claim 1 and is drawn to an “immunogenic fragment of the Rh factor” comprising “an epitope of Rh antigen”. However, Claim 1 already recites “an immunogenic fragment of an Rh factor”, and, according to the instant specification, an “epitope” and an “immunogenic fragment” are equivalent terms referring to the same structure (see ¶0043). Accordingly, Claim 2 fails to further limit the scope of the claim upon 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
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 1-18, 20, and 22 are rejected under 35 U.S.C. 103 as being unpatentable over Milone et al. 2019 (US 2019/0153064 A1; PTO-892), herein “Milone”, and in view of Urbaniak and Barker 2005 (US 2005/0069544 A1; PTO-892), herein “Urbaniak”.
Milone teaches polypeptides and polynucleotides encoding said polypeptides comprising a chimeric alloantigen receptor (“CALLAR”) specific for an alloantibody (abstract; Milone claim 1) wherein said CALLAR comprises an extracellular domain comprising an alloantigen or fragment thereof, a transmembrane domain, an intracellular costimulatory domain, and an intracellular signaling domain (¶0006; ¶0009; Fig 1-2).
Regarding instant Claims 4-5, Milone teaches that the CALLAR comprises a CD8α signal peptide (Fig. 1) comprising an identical sequence to instantly claimed SEQ ID NO: 16 (see alignment with Milone SEQ ID NO: 22 below)
SEQ16 1 MALPVTALLLPLALLLHAARP 21
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Mil22 1 MALPVTALLLPLALLLHAARP 21
Regarding instant Claims 6-7, Milone teaches that the CALLAR comprises a CD8α transmembrane domain (Fig. 1) comprising an identical sequence to instantly claimed SEQ ID NO: 17 (see alignment with Milone SEQ ID NO: 8 below)
SEQ17 1 IYIWAPLAGTCGVLLLSLVIT 21
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Mil8 1 IYIWAPLAGTCGVLLLSLVIT 21
Regarding instant Claims 8-9, Milone teaches that the CALLAR comprises a CD8α hinge region linking the extracellular domain to the transmembrane domain (Fig. 1; Fig. 2).
Regarding instant Claim 10, Milone teaches that alternatively the extracellular domain can be linked to the transmembrane domain by a GS linker (Fig. 2, second structure) wherein the GS domain comprises a sequence identical to instant SEQ ID NO: 19 (see alignment with Milone SEQ ID NO: 28 below)
SEQ19 1 GGGGSGGGGSSG 12
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Mil28 185 GGGGSGGGGSSG 196
Regarding instant Claim 11-15, Milone teaches that the intracellular signaling domain comprises a CD137 costimulatory domain and CD3ζ signaling domain, comprising sequences identical to instantly claimed SEQ ID NOs: 20 and 21, respectively (see alignments with Milone SEQ ID NOs: 14 below).
SEQ20 1 KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL 42
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Mil14 463 KRGRKKLLYIFKQPFMRPVQTTQEEDGCSCRFPEEEEGGCEL 504
SEQ21 1 RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYN 60
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Mil14 505 RVKFSRSADAPAYQQGQNQLYNELNLGRREEYDVLDKRRGRDPEMGGKPRRKNPQEGLYN 564
SEQ21 61 ELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 112
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Mil14 565 ELQKDKMAEAYSEIGMKGERRRGKGHDGLYQGLSTATKDTYDALHMQALPPR 616
Regarding instant Claims 17-18, Milone teaches vectors comprising the polynucleotide encoding the CALLAR, including plasmids and viral vectors, wherein the polynucleotide is operatively linked to a promoter sequence to drive expression of the CALLAR polypeptide (Pg. 11-13, § Vector Comprising the CALLAR).
Regarding instant Claim 20, Milone teaches engineered cells comprising a polynucleotide encoding the CALLAR (Pg. 13, § Cells Comprising a CALLAR).
Regarding instant Claim 22, Milone teaches a method of treating a subject in need thereof comprising administering T cells expressing the CALLAR (Pg. 17-18, § Therapy).
Milone teaches that T cells transduced with a CALLAR effectively mediate lysis of cells having surface expression of the target alloantibody, but not control cells (¶0232).
Milone further suggests that the CALLAR approach could be employed in managing alloreactive antibodies as an alternative to immune tolerance induction, which has previously shown only limited success (¶0003).
Milone does not teach that the extracellular domain of the CALLAR comprises an immunogenic fragment of an Rh factor. This deficiency is cured by Urbaniak.
Urbaniak teaches that complications can occur during pregnancy when a mother who is RhD negative is carrying a RhD positive fetus. Alloimmunization by the RhD positive blood of the mother’s own baby can result in the mother producing anti-RhD antibodies which can cross the placenta and cause Rh haemolytic disease in a neonate (¶0005-0006).
Urbaniak teaches the identification of immunogenic Rh fragments by means of screening a library of Rh peptides for their ability to induce proliferation in peripheral blood mononuclear cells isolated from donors previously alloimmunized with RhD-positive blood through either pregnancy or transfusion (Example 1).
Urbaniak teaches a method of using these immunogenic fragments to prevent alloreactivity to the Rh factor in a process known as immune tolerization, whereby repeated low-level exposure to an antigen over a period of time trains the immune system to no longer recognize the antigen as foreign, preventing a future immune response to said antigen (¶0018; Urbaniak claim 34).
Regarding instant Claims 2-3, Urbaniak teaches many immunogenic fragments of the Rh factor including Urbaniak SEQ ID NO: 14 – which comprises all but one amino acid from instantly claimed SEQ ID NO: 6 (as recited in instant Table 2; see alignment below).
SEQ6 2 PSGKVVITLFSIRL 15
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Urb14 1 PSGKVVITLFSIRL 14
It would have been obvious to one of ordinary skill in the art to substitute the antigenic fragment in the CALLAR taught by Milone with an antigenic fragment of the Rh factor as taught by Urbaniak, resulting in a chimeric alloantigen receptor comprising an extracellular antigenic fragment of an Rh factor, a hinge region, a transmembrane region, a costimulatory domain, and a primary signaling domain which can be used to redirect T cell cytotoxicity towards cells expressing antibodies against the Rh factor, thereby treating Rh factor alloimmunization.
The skilled artisan would have been motivated to do so because Urbaniak teaches that alloimmunization against Rh can cause complications during pregnancy, and although Urbaniak teaches that the antigenic Rh fragments can be employed in to encourage immune tolerance, Milone teaches that immune tolerance induction has shown limited success – and that as an alternative CALLAR cells can specifically target cells that produce the alloantibodies. There would have been a reasonable expectation of success because Urbaniak teaches a variety of antigenic fragments responsible for Rh factor alloreactivity, and Milone teaches that CALLAR-expressing cells effectively lyse cells expressing the target antibodies.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to BRYAN WILLIAM HECK whose telephone number is (703)756-4701. The examiner can normally be reached Mon-Fri 8:00am - 5:30pm.
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If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Julie Wu can be reached at (571) 272-5205. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
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/BRYAN WILLIAM HECK/ Examiner, Art Unit 1643
/JULIE WU/ Supervisory Patent Examiner, Art Unit 1643