Office Action 1: Non-Final Rejection (2024-04-04)
Rejection types: 112 - Written Description/Enablement

CLAIMS:
Amendments to the Claims

Please cancel Claims 10-12, 21-23, 26, 40-41, and 48. Please amend Claims 2, 3, 5-6, 8- 9, 13, 16-17, 19-20, 24-25, 27, 30-31, 33-35, 38-39, 42-45, 47, and 49.

The amendments are made to expedite prosecution of this application. Applicant is not conceding that the claims prior to amendment are not patentable. No inference should be made that applicant is disclaiming any subject matter of the present application, and applicant reserves the right to pursue the unamended claims or any other broader or narrower claims supported by the disclosure at a later date, including in one or more continuing applications.

The Claim Listing below will replace all prior versions of the claims in the application: Claim Listing

1\. (Original) A method of measuring the activity of a FAMIN protein comprising;
providing an isolated FAMIN protein; and
determining the adenosine deaminase activity, purine nucleoside phosphorylase activity and/or methylthioadenosine phosphorylase activity of the FAMIN protein.

2\. (Currently Amended) A method of screening for a compound that modulates the activity of a FAMIN protein comprising;
determining the adenosine deaminase activity, purine nucleoside phosphorylase activity and/or methylthioadenosine phosphorylase activity of an isolated FAMIN protein in the presence and absence of a test compound, wherein a difference in the adenosine deaminase activity, purine nucleoside phosphorylase activity and/or methylthioadenosine phosphorylase activity of the FAMIN protein in the presence relative to the absence of test compound is indicative that the test compound modulates the activity of the FAMIN protein inhibitor.

3\. (Currently Amended) A method according to claim 2 wherein a decrease in the adenosine deaminase activity, purine nucleoside phosphorylase activity and/or methylthioadenosine phosphorylase activity of the FAMIN protein in the presence relative to the absence of test compound is indicative that the test compound is a FAMIN inhibitor.

4\. (Original) A method according to claim 2 wherein an increase in the adenosine deaminase activity, purine nucleoside phosphorylase activity and/or methylthioadenosine phosphorylase activity of the FAMIN protein in the presence relative to the absence of test compound is indicative that the test compound is a FAMIN potentiator.

5\. (Currently Amended) A method according to claim 1 wherein the purine nucleoside phosphorylase activity is an adenosine phosphorylase activity.

6\. (Currently Amended) A method according to claim 1 wherein the adenosine deaminase activity of the FAMIN protein is determined by measuring the conversion of an adenosine molecule into an inosine molecule in the presence of the FAMIN protein.

7\. (Original) A method according to claim 6 wherein the method comprises contacting the isolated FAMIN protein with adenosine nucleoside in a reaction solution; and determining the amount of adenosine nucleoside or inosine nucleoside in the reaction solution following said contacting.

8\. (Currently Amended) A method according to claim 6 wherein a decrease in the concentration of adenosine nucleoside or an increase in the concentration of inosine nucleoside in the reaction solution is indicative of adenosine deaminase activity.

9\. (Currently Amended) A method according to claim 6 wherein;
(i) the adenosine molecule is adenosine and the inosine molecule is inosine; (ii) the adenosine molecule is deoxyadenosine and the inosine molecule is deoxyinosine (iii) the adenosine molecule is 2'-deoxyadenosine and the inosine molecule is 2'deoxyinosine; or (iv) the adenosine molecule is 5'-deoxyadenosine and the inosine molecule is 5'deoxyinosine.

10\. (Cancelled)
11\. (Cancelled)

12\. (Cancelled)

13\. (Currently Amended) A method according to claim 1 wherein the purine nucleoside phosphorylase activity of the FAMIN protein is determined by measuring the conversion of a purine nucleoside into a nucleobase and a ribose-1-phosphate molecule in the presence of the FAMIN protein.

14\. (Original) A method according to claim 13 wherein the method comprises contacting the isolated FAMIN protein with a purine nucleoside in a reaction solution; and determining the amount of purine nucleoside; or purine nucleobase and/or ribose-1-phosphate molecule in the reaction solution following said contacting.

15\. (Original) A method according to claim 14 wherein the reaction solution comprises inorganic phosphate.

16\. (Currently Amended) A method according to claim 13 \[\[to 15\]\] wherein a decrease in the concentration of purine nucleoside or an increase in the concentration of purine nucleobase and/or ribose-1-phosphate molecule in the reaction solution is indicative of purine nucleoside phosphorylase activity.

17\. (Currently Amended) A method according to claim 1 \[\[to 12\]\] wherein the purine nucleoside phosphorylase activity of the FAMIN protein is determined by measuring the conversion of a nucleobase and a ribose-1-phosphate molecule into a purine nucleoside in the presence of the FAMIN protein.

18\. (Original) A method according to claim 17 wherein the method comprises contacting the isolated FAMIN protein with a nucleobase and a ribose-1-phosphate molecule in a reaction solution; and determining the amount of purine nucleoside; or purine nucleobase and/or ribose-1- phosphate molecule in the reaction solution following said contacting.

19\. (Currently Amended) A method according to claim 17 \[\[or 18\]\] wherein a decrease in the concentration of nucleobase and a ribose-1-phospate molecule or an increase in the concentration of purine nucleoside in the reaction solution is indicative of purine nucleoside phosphorylase activity.

20\. (Currently Amended) A method according to claim 13 wherein (i) the purine nucleoside is guanosine, the purine nucleobase is guanine and the ribose-1- phosphate molecule is a-D-ribose-1-phosphatei (ii) the purine nucleoside is adenosine, the purine nucleobase is adenine and the ribose-1- phosphate molecule is a\-D-ribose-1\-phosphate;
(iii) the purine nucleoside is 2'-deoxyadenosine, the purine nucleobase is adenine and the ribose- 1-phosphate molecule is 2' deoxy a\-D-ribose-1\-phosphate; or
(iv) the purine nucleoside is 5'-deoxyadenosine, the purine nucleobase is adenine and the ribose- 1-phosphate molecule is 5' deoxy a\-D-ribose-1\-phosphate.

21\. (Cancelled)

22\. (Cancelled)

23\. (Cancelled)

24\. (Currently Amended) A method according to claim 13 wherein the purine nucleoside is an inosine molecule.

25\. (Currently Amended) A method according to claim 24 wherein (i) the inosine molecule is inosine, the purine nucleobase is hypoxanthine and the ribose-1- phosphate molecule is a-D-ribose-1-phosphate; or
(ii) the inosine molecule is deoxvinosine; the purine nucleobase is hypoxanthine and the ribose- 1-phosphate molecule is 2'deoxy-a\-D-ribose-1\-phosphate.
26\. (Cancelled)

27\. (Currently Amended) A method according to claim 1 wherein the methylthioadenosine phosphorylase activity of the FAMIN protein is determined by measuring the conversion of methylthioadenosine into adenine and a methylthioribose- 1-phosphate molecule in the presence of the FAMIN protein.

28\. (Original) A method according to claim 27 wherein the method comprises contacting the isolated FAMIN protein with a methylthioadenosine nucleoside in a reaction solution; and
determining the amount of methylthioadenosine nucleoside; or adenine nucleobase and/or methylthioribose-1-phosphate molecule in the reaction solution following said contacting.

29\. (Original) A method according to claim 28 wherein the reaction solution comprises inorganic phosphate.

30\. (Currently Amended) A method according to claim 28 \[\[or 29\]\] wherein a decrease in the concentration of methylthioadenosine nucleoside or an increase in the concentration of adenine nucleobase and/or methylthioribose-1-phosphate molecule in the reaction solution is indicative of methylthioadenosine phosphorylase activity.

31\. (Currently Amended) A method according to claim 1 wherein the methylthioadenosine phosphorylase activity of the FAMIN protein is determined by measuring the conversion of adenine nucleobase and a methylthioribose-1-phosphate molecule into methylthioadenosine nucleoside in the presence of the FAMIN protein.

32\. (Original) A method according to claim 31 wherein the method comprises contacting the isolated FAMIN protein with adenine nucleobase and a methylthioribose-1-phosphate molecule in a reaction solution; and determining the amount of methylthioadenosine nucleoside; or
adenine nucleobase and/or methylthioribose-1-phosphate molecule in the reaction solution following said contacting.

33\. (Currently Amended) A method according to claim 31 \[\[or 32\]\] wherein a decrease in the concentration of adenine nucleobase and/or methylthioribose-1-phosphate molecule or an increase in the concentration of methylthioadenosine nucleoside in the reaction solution is indicative of methylthioadenosine phosphorylase activity.

34\. (Currently Amended) A method according to claim 27 wherein the methylthioadenosine nucleoside is 5-methylthioadenosine and the methylthioribose-1- phosphate molecule is S-methyl-5-thio-a-D-ribose-1-phosphate.

35 (Currently Amended) A method according to claim 1 comprising determining the adenosine deaminase activity and purine nucleoside phosphorylase activity of the FAMIN molecule.

36\. (Original) A method according to claim 35 wherein the method comprising contacting the FAMIN protein with adenosine nucleoside in a reaction solution; and determining the amount of adenosine nucleoside or hypoxanthine and/or ribose-1-phosphate molecule in the reaction solution following said contacting.

37\. (Original) A method according to claim 36 wherein the reaction solution comprises inorganic phosphate.

38\. (Currently Amended) A method according to claim 36 \[\[or 37\]\] wherein a decrease in the concentration of adenosine nucleoside or an increase in the concentration of hypoxanthine and/or ribose-1-phosphate molecule in the reaction solution is indicative of adenosine deaminase and purine nucleoside phosphorylase activity.

39\. (Currently Amended) A method according to claim 36 wherein (i) the adenosine nucleoside is adenosine and the ribose-1-phosphate molecule is a-D-ribose-1- phosphate.

(ii) the adenosine nucleoside is 2'-deoxyadenosine and the ribose-1\-phosphate is 2'deoxy-a\-D- ribose-1\-phosphate; or (iii) the adenosine nucleoside is 5'-deoxyadenosine and the ribose-1\-phosphate is 5' deoxy-a\-D- ribose- 1\-phosphate.

40\. (Cancelled)

41\. (Cancelled)

42\. (Currently Amended) A method according to claim 1 comprising determining the adenosine deaminase activity, purine nucleoside phosphorylase activity and methylthioadenosine phosphorylase activity of the FAMIN protein.

43\. (Currently Amended) A method according to claim 1 comprising determining the adenosine deaminase activity and the methylthioadenosine phosphorylase activity of the FAMIN protein.

44\. (Currently Amended) A method according to claim 1 comprising determining the purine nucleoside phosphorylase activity and the methylthioadenosine phosphorylase activity of the FAMIN protein.

45\. (Currently Amended) A method according to claim 1 wherein the FAMIN protein is human FAMIN.

46\. (Original) A method according to claim 45 wherein the FAMIN protein comprises an amino acid sequence having at least 80% identity to the sequence of amino acids 176-430 of NP\_001121775.1.

47\. (Currently Amended) A method according to claim 45 wherein the FAMIN protein comprises an Ile residue or a Val residue at a position corresponding to position 254 of the amino acid sequence of NP\_001121775.1 (SEQ ID NO: 1).
48\. (Cancelled)

49\. (Currently Amended) A method according to claim 1 comprising identifying a test compound that inhibits FAMIN activity and optionally isolating and/or purifying the identified test compound.
\-2- -3- -4- -5- -6- -7- -8- -9- 3487631.v1

OFFICE ACTION:
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 .
Response to Amendment
The amendment received on 12/13/2021 is acknowledged.  Claims 2-3, 5-6, 8-9, 13, 16-17, 19-20, 2427, 30-31, 33-35, 38-39, 42-45 and 49 have been amended.  Claims 10-12, 21-23, 26, 40-41, and 48 have been cancelled.   Claims 1-9, 13-20, 24-25, 27-39, 42-47, and 49 are currently pending and have been treated on the merits.
Claim Objections
Claims 46 and 47 are objected to because of the following informalities:
Claims 46 and 47 recite the limitation “NP_001121775.1”, this term appears to be an accession number, amendment to refer to the disclosed SEQ ID NO:1, outside of parentheses, would be appropriate as this sequence is disclosed and provides the full description self contained within the instant application rather than referring to an outside source.
Appropriate correction is required.
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 2-4, 28-30, 32, 36-39, 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.
Regarding claim 2 and claims 3-4 dependent thereon, Claim 2 recites the limitation the FAMIN protein inhibitor in the last line.  There is insufficient antecedent basis for this limitation in the claim.  IT is unclear what applicant is claiming as no inhibitor has been claimed.  It appears that inhibitor might be an extra word, in which case deleting it would provide clarity.  Alternatively, if an inhibitor is present, adding limitations to give antecedent basis and make it apparent where the inhibitor is in the method would provide clarity.
Regarding Claims 28 and 32, and claims 29-30 dependent thereon, Claims 28 and 32 recite the limitation “… determining the amount of methylthioadenosine nucleoside; or adenine nucleobase and/or methylthioribose-1-phosphate molecule in the reaction solution following said contacting.”  As currently written and punctuated it is unclear exactly what is being claimed.  The use of semicolons are used to separate steps, and the use of multiple “or” as well as an “and” make it unclear what is being claimed as it is unclear if methylthioadenosine nucleoside must be determined, or what substrate or product must be detected.  Amendment to read “… determining the amount of methylthioadenosine nucleoside,[[; or]] adenine nucleobase and/or methylthioribose-1-phosphate molecule in the reaction solution following said contacting” would provide clarity.
Regarding claim 36 and claims dependent thereon and the limitation “and determining the amount of adenosine nucleoside, or hypoxanthine, and/or ribose-1-phosphate molecule in the reaction solution following said contacting.”  As currently worded it is unclear what is being claimed as it is unclear if either adenosine nucleotide is detected or hypoxanthine and/or ribose-1-phopshate, or if adenosine nucleotide may be detected along with hyopxanthine, ribose-1-phosphate or all three.  Amendment to “and determining the amount of adenosine nucleoside, [[or]] hypoxanthine, and/or ribose-1-phosphate molecule in the reaction solution following said contacting.” would provide clarity if the intent is any one of the components may be detected as well as all three.  Alternatively a Markush group may be used.
Allowable Subject Matter
Claims 1, 5-9, 13-20, 24-25, 27, 31, 33-35, 42-45 and 49 are allowed.
The following is an examiner’s statement of reasons for allowance:
The closest prior art is represented by Cader (“C13orf31 (FAMIN) is a central regulator of immunometabolic function”, Nature Immunology, Vol. 17, No. 9, 2016/IDS submitted).
At the time of invention FAMIN was an orphan protein of unknown activity.  Applicants have discovered its enzymatic activities.  Applicant’s invention is thus found novel and non-obvious, as the claimed assays for a previously unknown activity are not taught or made obvious by the prior art.
Any comments considered necessary by applicant must be submitted no later than the payment of the issue fee and, to avoid processing delays, should preferably accompany the issue fee.  Such submissions should be clearly labeled “Comments on Statement of Reasons for Allowance.”
Conclusion
Claims 1, 5-9, 13-20, 24-25, 27, 31, 33-35, 42-45 and 49 are allowed.
Claims 2-4, 28-30, 32, 36-39 are rejected.
Claims 46-47 are objected to.

APPLICANT REBUTTAL: REMARKS
Amendments to the Claims
Claims 2, 28, 32, 36 and 46-47 have been amended. Claim 2 has been amended to delete
"inhibitor." Support for the amendments is found, for example, in originally-filed claims 1 and 2.
Claims 28, 32 and 36 have been amended to delete "or." Support for the amendments is found,
for example, in originally-filed claims 28, 32 and 36, respectively. Claims 46-47 have been amended to remove the NP number. Support for the amendments is found, for example, in
originally-filed claim 47.
The amendments are made to expedite prosecution of this application. Applicant is not
conceding that the claims prior to amendment are not patentable. No inference should be made
that Applicant is disclaiming any subject matter of the present application, and Applicant
reserves the right to pursue the unamended claims or any other broader or narrower claims
supported by the disclosure at a later date, including in one or more continuing applications.
Cancellation of any claim herein is without prejudice to reinstatement in this or continuing
application.
No new matter has been added. Entry of the amendment to the claims is respectfully
requested.
Obj
ections
In the action, the limitation "NP 001121775.1" in claims 46 and 47 was deemed
allegedly objectionable. Solely to expedite prosecution, the claims have been amended to replace
the limitation with "SEQ ID NO: 1" in claims 46 and 47. Withdrawal of the objection is
respectfully requested.
Rej
ection Under 35 U.S.C.
&
In the action, previous claims 2-4, 28-30, 32 and 36-39 were alleged to be indefinite.
Solely to expedite prosecution, claim 2 has been amended to delete the term "inhibitor."
Claims 3-4 depend from claim 2 and contain the elements of the claim from which they depend.
Solely to expedite prosecution, claims 28, 32 and 36 have been amended to delete the
superfluous term "or." Claims 29-30 depend from claim 28, and claims 37-39 depend from claim
39, and contain the elements of the claim from which they depend.
Withdrawal of the rejections is respectfully requested.
Information Disclosure Statement
An Information Disclosure Statement (IDS) is being filed concurrently herewith. Entry
of the IDS is respectfully requested.
Payment of Fees
Authorization is hereby granted to charge the fees due with this submission, including
any extension of time fee, to Deposit Account No. 08-0380.
CONCLUSION

NEXT OFFICE ACTION: 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 .
Response to Amendment
The amendment received on 07/02/2024 is acknowledged.  Claims 2, 28, 32, 36 and 46-47 have been amended.
In light of the amendment to the claims the rejections under 35 U.S.C. 112(b) have been withdrawn, and the objection to claims 46-47 have been obviated.
Conclusion
Claims 1-9,13-20,24-25,27-39,42-47 and 49 are allowed.

CITED REFERENCE SUMMARIES: Ref US20220017900A1: Claims:
A method of treating cancer in an individual in need thereof comprising reducing FAMIN activity in the individual.
A method of stimulating a cell-mediated immune response in an individual in need thereof comprising reducing FAMIN activity in the individual.
A method according to claim 2 wherein the individual has cancer and the method is a method of cancer immunotherapy.
A method according to claim 2 wherein the individual has an infection and the method is a method of immunotherapy.
A method according to any one of the preceding claims wherein the method comprises administering an agent which reduces FAMIN activity to the individual.
A method according to claim 5 wherein the agent is a FAMIN antagonist.
A method according to claim 6 wherein the FAMIN antagonist is an organic compound having a molecular weight of 900 Da or less.
A method according to claim 7 wherein the FAMIN antagonist comprises 3â²-deoxy-N-(1-oxododecyl) adenosine, pentostatin, EHNA, 8-aminoguanosine, MT-ImmA or MT-DADMe-ImmA (MTDIA) or a pharmaceutically acceptable salt, solvate, or derivative of any one of these.
A method according to claim 5 wherein the agent is a suppressor nucleic acid that reduces expression of active FAMIN polypeptide.
A method according to claim 9 wherein the suppressor nucleic acid is a siRNA or shRNA.
A method according to claim 10 wherein the suppressor nucleic acid comprises a nucleotide sequence at least 95% identical to a contiguous sequence of 15 to 40 nucleotides of SEQ ID NO: 2.
A method according to claim 9 wherein the suppressor nucleic acid is an antisense oligonucleotide.
A method according to claim 5 wherein the agent is a targeted nuclease that reduces expression of active FAMIN polypeptide to the individual.
A method according to claim 13 wherein the targeted nuclease is a ZFN, TALEN or meganuclease that recognises a target sequence within the FAMIN gene.
A method according to claim 13 wherein the targeted nuclease is a CRISPR associated nuclease, said CRISPR associated nuclease being administered in combination with a guide RNA that recognises a target sequence within the FAMIN gene.
A method according to claim 14 or claim 15 wherein the targeted nuclease cleaves genomic DNA at the target sequence of the FAMIN gene, thereby causing a deletion or insertion which reduces expression of active FAMIN polypeptide.
A method according to any one of claims 5 to 16 wherein the agent is administered in combination with an additional therapeutic agent.
A method according to claim 17 wherein the additional therapeutic agent is an immune checkpoint inhibitor.
A method according to claim 18 wherein the additional therapeutic agent is an anti-cancer agent.
An agent which reduces FAMIN activity for use in a method according to any one of claims 5 to 19 .
Use of an agent which reduces FAMIN activity in the manufacture of a medicament for use in a method according to any one of claims 5 to 19 .
A pharmaceutical composition comprising an agent as defined in any one of claims 5 to 20 in combination with an additional therapeutic agent, and further comprising a pharmaceutically acceptable excipient.
A pharmaceutical composition according to claim 22 , wherein the additional therapeutic agent is an anti-cancer agent.
A method of stimulating cell-mediated immune responses comprising administering to an individual in need thereof; (a) a population of FAMIN deficient immune cells; or (b) a population of T cells activated in vitro by a population of FAMIN deficient immune cells.
(a) a population of FAMIN deficient immune cells; or
(b) a population of T cells activated in vitro by a population of FAMIN deficient immune cells.
A method according to claim 24 wherein the individual has cancer and the method is a method of cancer immunotherapy.
A method according to claim 24 wherein the individual has an infection and the method is a method of immunotherapy.
A population of FAMIN deficient immune cells; or a population of T cells activated in vitro by a population of FAMIN deficient immune cells for use in a method according to any one of claims 24 to 26 .
Use of a population of FAMIN deficient immune cells; or a population of T cells activated in vitro by a population of FAMIN deficient immune cells for use in in the manufacture of a medicament for use in a method according to any one of claims 24 to 26 .
An in vitro method of activating T cells comprising; providing a population of naÃ¯ve T cells, culturing the T cells with a population of FAMIN deficient immune cells, thereby producing an activated T cell population.
providing a population of naÃ¯ve T cells,
culturing the T cells with a population of FAMIN deficient immune cells,
thereby producing an activated T cell population.
A method according to claim 29 wherein the immune cells display a target antigen and the activated T cell population are specific for the displayed target antigen.
A method according to claim 29 or claim 30 wherein the activated T cell population may have increased cytolytic activity relative to T cells activated with control immune cells.
A method according to any one of claims 24 to 31 wherein the FAMIN deficient immune cells have reduced FAMIN activity.
A method according to any one of claims 24 to 31 wherein the FAMIN deficient immune cells have no FAMIN activity.
A method according to any one of claims 24 to 33 wherein the immune cells are macrophages or dendritic cells.
A method according to any one of claims 24 to 34 wherein expression of active FAMIN polypeptide is reduced in the FAMIN deficient cells relative to control immune cells.
A method according to any one of claims 24 to 35 wherein the FAMIN deficient cells display no expression of active FAMIN polypeptide.
A method according to any one of claims 24 to 36 wherein the FAMIN deficient cells express a suppressor nucleic acid which reduces the expression of active FAMIN polypeptide
A method according to any one of claims 24 to 36 wherein the FAMIN deficient cells comprise one or more mutations in the FAMIN gene which reduce the expression of active FAMIN polypeptide.
A method according to claim 38 wherein the one or more mutations are insertions or deletions.
A method according to claim 39 wherein the one or more mutations are introduced by targeted mutagenesis.
A method according to any one of claims 24 to 40 wherein the population of FAMIN deficient immune cells is produced by a method comprising; providing a population of immune cells obtained from a donor individual, reducing FAMIN activity in the immune cells to produce a population of FAMIN deficient immune cells, and culturing the FAMIN deficient immune cells.
providing a population of immune cells obtained from a donor individual,
reducing FAMIN activity in the immune cells to produce a population of FAMIN deficient immune cells, and
culturing the FAMIN deficient immune cells.
A method according to any one of claims 24 to 40 wherein the population of FAMIN deficient immune cells is produced by a method comprising; providing a population of immune progenitor cells from sample obtained from a donor individual, reducing FAMIN activity in the immune progenitor cells to produce a population of FAMIN deficient immune progenitor cells, and differentiating the FAMIN deficient immune progenitor cells to produce a population of FAMIN deficient immune cells.
providing a population of immune progenitor cells from sample obtained from a donor individual,
reducing FAMIN activity in the immune progenitor cells to produce a population of FAMIN deficient immune progenitor cells, and
differentiating the FAMIN deficient immune progenitor cells to produce a population of FAMIN deficient immune cells.
A method according to claim 41 or claim 42 wherein FAMIN activity is reduced by nucleic acid suppression.
A method according to claim 43 wherein FAMIN activity is reduced by expressing in the immune cells or immune progenitor cells a suppressor nucleic acid which reduces the expression of active FAMIN polypeptide
A method according to claim 41 or claim 42 wherein FAMIN activity is reduced by targeted mutagenesis.
A method according to claim 45 wherein FAMIN activity is reduced by expressing in the immune cells or immune progenitor cells a targeted nuclease which abolishes the expression of active FAMIN polypeptide
A method according to any one of claims 24 to 46 wherein the T cells are CD8+ cytotoxic T cells.
A method according to any one of claims 24 to 47 wherein the population of FAMIN deficient immune cells or T cells is administered in combination with a population of T cells to the individual.
A population of FAMIN deficient immune cells and/or population of T cells activated in vitro by a population FAMIN deficient immune cells for use in a method according to any one of claims 24 to 48 .
A pharmaceutical composition comprising a population of FAMIN deficient immune cells and/or a population of T cells activated by FAMIN deficient immune cells.
A method of screening for a compound useful in a method according to any one of claims 1 to 4 comprising; determining the activity of an isolated FAMIN protein in the presence and absence of a test compound, a decrease in the activity of a FAMIN protein in the presence relative to the absence of the test compound being indicative that the compound may be useful in said method.
determining the activity of an isolated FAMIN protein in the presence and absence of a test compound,
a decrease in the activity of a FAMIN protein in the presence relative to the absence of the test compound being indicative that the compound may be useful in said method.