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 .
Election
Applicant's election without traverse of the following species in the reply filed on 08/05/2026 is acknowledged: An anti-human transferrin receptor (TfR) antibody comprising HCDR1-3 and LCDR1-3 comprising SEQ ID NOs: 26, 28, 7, 29, 10, and 11, respectively, corresponding VH and VL sequences are SEQ ID NOs: 21 and 25, respectively, and the disclosed amino acid sequences of said antibody include SEQ ID NOs: 30-34.
In an effort to expedite compact prosecution, all species encompassed in the instant claims have been rejoined.
Status of Claims
Claims 35, 38, 39, 41, 42, 44, 45, 47-53 and 55-60 are currently pending.
Claims 35, 38, 44 and 45 are amended.
Claims 55-60 are new.
Claims 35, 38, 39, 41, 42, 44, 45, 47-53 and 55-60 are currently under examination on the merits.
Information Disclosure Statement
The information disclosure statement is being considered by the examiner.
Claim Objections
Claim 35 is objected to because of the following informalities:
Claim 35 recites the abbreviation “(TfR)” after the term or phrase “anti-human transferrin receptor”. To be consistent with claim 58, it is suggested that the recitation of “(TfR)” in claim 35 be amended to “(hTfR)”.
Appropriate correction is required.
Claim 41 is objected to as being dependent on a rejected base claim (claim 35).
Claim Rejections - 35 USC § 112(b)
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 38 is rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AlA), 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-AlA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 38 recites the phrase “…..and H435R and Y436F mutations that facilitate purification (Eu numbering)”. It is unclear if the limitation in parentheses is part of the claimed invention, is exemplary or is a further limitation. Further, it is unclear whether the limitation in parenthesis is only applied to H435R and Y436F mutations. Therefore, the metes-and-bounds of the claim are unclear. In an effort to expedite prosecution, the following amendment to claim 38 is suggested to obviate this rejection: “…..and H435R and Y436F mutations that facilitate purification, wherein the numbering is according to Eu numbering
Claim Rejections 35 U.S.C.112(a) (First)
The following is a quotation of the first paragraph of 35 U.S.C. 112(a):
(a) IN GENERAL.—The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor or joint inventor of carrying out the invention.
The following is a quotation of the first paragraph of pre-AIA 35 U.S.C. 112:
The specification shall contain a written description of the invention, and of the manner and process of making and using it, in such full, clear, concise, and exact terms as to enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the same, and shall set forth the best mode contemplated by the inventor of carrying out his invention.
Claims 35, 38, 39, 42, 44, 47-53, 55 and 58-60 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, as failing to comply with the written description requirement. The claim(s) contains subject matter which was not described in the specification in such a way as to reasonably convey to one skilled in the relevant art that the inventor or a joint inventor, or for pre-AIA the inventor(s), at the time the application was filed, had possession of the claimed invention.
In the instant case, claims 35, 38, 39, 42, 44, 47-53 and 55, as recited in part a) of claim 35, are inclusive of a genus of anti-human transferrin receptor (hTfR) antibodies or antigen-binding fragments thereof, wherein the antibody or antigen-binding fragment comprises:
a heavy chain CDR (HCDR) 1 comprising GYTFTRYY (SEQ ID NO: 26), or GYTFTRYW (SEQ ID NO: 27), or DYTFTRYW (SEQ ID NO: 5),
an HCDR2 comprising IDPSVSET (SEQ ID NO: 28) or IDPSVSEC (SEQ ID NO: 6),
an HCDR3 comprising SQIRLPYYYAMDS (SEQ ID NO: 7),
a light chain CDR (LCDR) 1 comprising QDISSF (SEQ ID NO: 29) or QDINSF (SEQ ID NO: 9), and
an LCDR2 comprising YTS (SEQ ID NO: 10),
without any LCDR3 for the full set of six CDRs that are responsible for the function of hTfR antigen binding, which means LCDR3 can be any amino acid sequence which is equivalent to any number of possible mutations for LCDR3. All dependent claims of claim 35 except claim 41 are included in this rejection. Claim 41 is not included in this rejection because the anti-hTfR antibody or antigen-binding fragment comprising: a) a heavy chain comprising SEQ ID NO: 32 and a light chain comprising SEQ ID NO: 31; b) a heavy chain comprising SEQ ID NO: 30 and a light chain comprising SEQ ID NO: 31; or c) a heavy chain comprising SEQ ID NO: 33, a light chain comprising SEQ ID NO:31, and an Fc polypeptide comprising SEQ ID NO: 34, comprise a full set of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 that are fully defined by their amino acid sequence.
Further, claims 58-60 are inclusive of a genus of anti-human transferrin receptor (TfR) antibodies or antigen-binding fragments thereof, wherein the antibody or antigen-binding fragment thereof comprises a paratope comprising a) heavy chain variable (VH) amino acid residues as recited in the claims; and b) light chain variable region (VL) amino acid residues as recited in the claims, which fails to define any of the six CDRs of the antibodies or antigen binding fragments thereof that function to bind hTfR.
However, the written description in this case only sets forth seven species of anti-human transferrin receptor (hTfR) antibodies or antigen-binding fragments thereof as disclosed in Table 2 (Pg 47-48) and paragraphs [01033], [0142] and [0198] of the instant specification and as summarized in the table below.
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Therefore, only seven specific combinations of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 that are recited in claim 35 were shown to bind hTfR as disclosed in the instant specification. The specification does not disclose, and the art does not teach, the genus of anti-hTfR antibodies or antigen-binding fragments thereof as broadly encompassed in the claims.
As is well-known in the antibody art at the time of filing, the specificity of an antibody is dependent upon the six CDR regions and different combinations of CDR sequences greatly alter antigen binding. It is well established that the formation of an intact antigen-binding site generally requires the association of the complete heavy and light chain variable regions of a given antibody, each of which consists of three CDRs which provide the majority of the contact residues for the binding of the antibody to its target epitope (reviewed in Sela-Culang et al. Frontiers in immunology 4 (2013): 302). The amino acid sequences and conformations of each of the heavy and light chain CDRs are critical in maintaining the antigen binding specificity and affinity which is characteristic of the parent immunoglobulin. Even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proceedings of the National Academy of Sciences, 1982, 79:1979-1983). Rudikoff et al. teaches that the alteration of a single amino acid in the CDR of a phosphocholine-binding myeloma protein resulted in the loss of antigen-binding function. Therefore, there is insufficient evidence or nexus that would lead the skilled artisan to predict the ability of a scFv to bind to CD28 or a Fab to bind to PD-L1 comprising mutations in any of the six CDR regions, or comprising mixing and matching a known set of three CDRs with an undefined set of three CDRs, which is also a form of introducing mutations into the CDR regions.
A description of a genus may be achieved by means of a recitation of a representative number of species falling within the scope of the genus or by describing structural features common to that genus that “constitute a substantial portion of the genus.” See University of California v. Eli Lilly and Co., 119 F.3d 1559, 1568, 43 USPQ2d 1398, 1406 (Fed. Cir. 1997): “A description of a genus of cDNAs may be achieved by means of a recitation of a representative number of cDNA, defined by nucleotide sequence, falling within the scope of the genus or of a recitation of structural features common to the members of the genus, which features constitute a substantial portion of the genus.”
The inventions at issue in Lilly were DNA constructs per se, the holdings of that case is also applicable to claims such as those at issue here.
Regarding claims to a product defined by function, without a correlation between structure and function, the claim does little more than define the claimed invention by function. That is not sufficient to satisfy the written description requirement. See Eli Lilly, 119 at1568 USPQ2d at 1406 (“definition by function…does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is”).
The instant specification fails to provide sufficient descriptive information, such as definitive structural features that are common to the genus. That is, the specification provides neither a representative number of anti-hTfR antibodies or antigen-binding fragments thereof that encompass the genus nor does it provide a description of structural features that are common to the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus. “[A] sufficient description of a genus . . . requires the disclosure of either a representative number of species falling within the scope of the genus or structural features common to the members of the genus so that one of skill in the art can ‘visualize or recognize’ the members of the genus.” Ariad, 598 F.3d at 1350 (quoting Eli Lilly, 119 F.3d at 1568-69). A “representative number of species” means that those species that are adequately described are representative of the entire genus. AbbVie Deutschland GMBH v. Janssen Biotech, 111 USPQ2d 1780, 1790 (Fed. Cir. 2014) (“The ’128 and ’485 patents, however, only describe species of structurally similar antibodies that were derived from Joe-9. Although the number of the described species appears high quantitatively, the described species are all of the similar type and do not qualitatively represent other types of antibodies encompassed by the genus.”). Thus, when there is substantial variation within the genus, one must describe a sufficient variety of species to reflect the variation within the genus to provide a "representative number” of species.
The functional requirements of the claimed antibodies are the sort of wish list of properties which fails to satisfy the written description requirement because “antibodies with those properties have not been adequately described.” Centocor, 636 F.3d at 1352. The “claims merely recite a description of the problem to be solved while claiming all solutions to it and . . . cover any compound later actually invented and determined to fall within the claim’s functional boundaries— leaving it to the pharmaceutical industry to complete an unfinished invention.” Ariad Pharmaceuticals, Inc. v. Eli Lilly and Co.,598 F.3d 1336, 1353 (Fed. Cir. 2010).
Since the disclosure fails to describe common attributes or characteristics that adequately identify members of the genus, and because the genus is highly variant, the disclosure of SEVEN SPECIES found in the specification is insufficient to describe the genus. Thus, one of skill in the art would reasonably conclude that the disclosure fails to provide a representative number of species to describe the genus as broadly claimed.
Vas-Cath Inc. v. Mahurkar, 19USPQ2d 1111, clearly states “applicant must convey with reasonable clarity to those skilled in the art that, as of the filing date sought, he or she was in possession of the invention. The invention is, for purposes of the ‘written description’ inquiry, whatever is now claimed.” (See page 1117.) The specification does not “clearly allow persons of ordinary skill in the art to recognize that [he or she] invented what is claimed.” (See Vas-Cath at page 1116). As discussed above, even though Applicant may propose methods of screening for possible members of the genus, the skilled artisan cannot envision the detailed chemical structure of the encompassed genus, and therefore conception is not achieved until reduction to practice has occurred, regardless of the complexity or simplicity of the method of isolation. Adequate written description requires more than a mere statement that it is part of the invention and reference to a potential method of isolation. The compound itself is required. See Fiers v. Revel, 25 USPQ2d 1601 at 1606 (CAFC 1993) and Amgen Inc. v. Chugai Pharmaceutical Co. Ltd., 18 USPQ2d 1016. See Ariad, 94 USPQ2d at 1161; Centocor at 1876 (“The fact that a fully-human antibody could be made does not suffice to show that the inventors of the '775 patent possessed such an antibody.”)
One cannot describe what one has not conceived. See Fiddes v. Baird, 30 USPQ2d 1481 at 1483. In Fiddes, claims directed to mammalian FGF’s were found to be unpatentable due to lack of written description for that broad class. The specification provided only the bovine sequence. Applicant is reminded that Vas-Cath makes clear that the written description provision of 35 U.S.C. §112 is severable from its enablement provision (see page 1115).
Claim Rejections 35 U.S.C.112(a) (Second)
Claims 35, 38, 39, 42, 44, 47-53 and 55 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for anti-human transferrin receptor (hTfR) antibodies or antigen-binding fragments thereof comprising a full set of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, does not reasonably provide enablement for antibodies or antigen-binding fragments thereof comprising only HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 without a LCDR3, as recited in claim 35 part a), which amounts to mutations in the CDR region. Further, claims 35, 38, 39, 42, 44, 47-53 and 55 are rejected under 35 U.S.C. 112(a) or 35 U.S.C. 112 (pre-AIA ), first paragraph, because the specification, while being enabling for anti-human transferrin receptor (hTfR) antibodies or antigen-binding fragments thereof comprising a full set of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, wherein the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 comprises the following combinations of SEQ ID NOs: 1) 5, 6, 7, 9, 10 and 11; 2) 26, 28, 7, 29, 10 and 11; 3) 27, 28, 7, 29, 10 and 11; 4) 5, 28, 7, 29, 10 and 11; 5) 26, 28, 7, 9, 10 and 11; 6) 27, 28, 7, 9, 10 and 11; and 7) 5, 28, 7, 9, 10 and 11, does not reasonably provide enablement for antibodies or antigen-binding fragments thereof comprising the combinations of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 of SEQ ID NOs: 8) 26, 6, 7, 29, 10 and 11; 9) 27, 6, 7, 29, 10 and 11; 10) 5, 6, 7, 29, 10 and 11; 11) 26, 6, 7, 9, 10 and 11; and 12) 27, 6, 7, 9, 10 as recited in claim 35 part b). The specification does not enable any person skilled in the art to which it pertains, or with which it is most nearly connected, to make and use the invention commensurate in scope with these claims.
Enablement is considered in view of the Wands factors (MPEP 2164.01 (a)). The court in Wands states: "Enablement is not precluded by the necessity for some experimentation such as routine screening. However, experimentation needed to practice the invention must not be undue experimentation. The key word is 'undue,' not 'experimentation."' (Wands, 8 USPQ2d 1404). Clearly, enablement of a claimed invention cannot be predicated on the basis of quantity of experimentation required to make or use the invention. "Whether undue experimentation is needed is not a single, simple factual determination, but rather is a conclusion reached by weighing many factual considerations." (Wands, 8 USPQ2d 1404). The factors to be considered in determining whether undue experimentation is required include: (A) The nature of the invention; (B) The breadth of the claims; (C) The amount of direction provided by the inventor; (D) The existence of working examples; (E) The state of the prior art; (F) The level of predictability in the art; (G) The quantity of experimentation needed to make or use the invention based on the content of the disclosure; and (H) The level of one of ordinary skill. While all of these factors are considered, a sufficient amount for a prima facie case are discussed below.
The nature of the invention
Claims 35, 38, 39, 42, 44, 47-53 and 55, as recited in claim 35 part a), are inclusive of a genus of anti-human transferrin receptor (hTfR) antibodies or an antigen-binding fragments thereof, wherein the antibody or antigen-binding fragment comprises:
a heavy chain CDR (HCDR) 1 comprising GYTFTRYY (SEQ ID NO: 26), or GYTFTRYW (SEQ ID NO: 27), or DYTFTRYW (SEQ ID NO: 5),
an HCDR2 comprising IDPSVSET (SEQ ID NO: 28) or IDPSVSEC (SEQ ID NO: 6),
an HCDR3 comprising SQIRLPYYYAMDS (SEQ ID NO: 7),
a light chain CDR (LCDR) 1 comprising QDISSF (SEQ ID NO: 29) or QDINSF (SEQ ID NO: 9), and
an LCDR2 comprising YTS (SEQ ID NO: 10),
without any LCDR3 for the full set of six CDRs that are responsible for the function of hTfR antigen binding, which means LCDR3 can be any amino acid sequence which is equivalent to any number of possible mutations for LCDR3. In addition, claims 35, 38, 39, 42, 44, 47-53 and 55, as recited in claim 35 part b), are inclusive of a genus of anti-human transferrin receptor (hTfR) antibodies or an antigen-binding fragments thereof, wherein the antibody or antigen-binding fragment comprises:
a heavy chain CDR (HCDR) 1 comprising GYTFTRYY (SEQ ID NO: 26), or GYTFTRYW (SEQ ID NO: 27), or DYTFTRYW (SEQ ID NO: 5),
an HCDR2 comprising IDPSVSET (SEQ ID NO: 28) or IDPSVSEC (SEQ ID NO: 6),
an HCDR3 comprising SQIRLPYYYAMDS (SEQ ID NO: 7),
a light chain CDR (LCDR) 1 comprising QDISSF (SEQ ID NO: 29) or QDINSF (SEQ ID NO: 9),
an LCDR2 comprising YTS (SEQ ID NO: 10), and
and LCDR3 comprising QQGNTLPRT (SEQ ID NO: 11),
which gives rise to twelve possible combinations for a full set of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 that are responsible for the function of hTfR antigen binding
The breadth of the claims
The claims are broad in that it encompasses mutants in the LCDR3 region of anti-human transferrin receptor (hTfR) antibodies or antigen-binding fragments thereof to any extent and every possible mutation because it is undefined in characteristics of length and amino acid sequence, that would retain the function of binding hTfR.
The claims are also inclusive of one of three possible sequences for HCDR1, one of two possible sequences for HCDR2, only one sequence for HCDR3, one of two possible sequences for LCDR1, only one sequence for LCDR2 and only one sequence for LCDR3, giving rise to twelve possible combinations of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 comprising the following SEQ ID NOs: (i) 26, 28, 7, 29, 10 and 11; (ii) 27, 28, 7, 29, 10 and 11; (iii) 5, 28, 7, 29, 10 and 11; (iv) 26, 6, 7, 29, 10 and 11; (v) 27, 6, 7, 29, 10 and 11; (vi) 5, 6, 7, 29, 10 and 11; (vii) 26, 28, 7, 9, 10 and 11; (viii) 26, 27, 7, 9, 10 and 11; (ix) 5, 28, 7, 9, 10 and 11; (x) 26, 6, 7, 9, 10 and 11; (xi) 27, 6, 7, 9, 10 and 11; and (xii) 5, 6, 7, 9, 10 and 11, that would retain the function of binding hTfR.
The amount of direction provided by the inventor/the existence of working examples
The specification at most discloses only seven species of anti-human transferrin receptor (hTfR) antibodies or antigen-binding fragments thereof as disclosed in Table 2 (Pg 47-48) and paragraphs [01033], [0142] and [0198] of the instant specification and as summarized in the table below.
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The disclosure does not discuss, or demonstrate through working examples, any novel derivatives, mutants, and/or variants of the LCDR3 for the anti-hTfR antibodies or antigen-binding fragments thereof that retain the instant claimed functionality of binding hTfR. In fact, only one LCDR3 of instant SEQ ID NO: 11 has been disclosed. The disclosure also does not demonstrate that combinations of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 comprising the following SEQ ID NOs (iv) 26, 6, 7, 29, 10 and 11; (v) 27, 6, 7, 29, 10 and 11; (vi) 5, 6, 7, 29, 10 and 11; (x) 26, 6, 7, 9, 10 and 11; and (xi) 27, 6, 7, 9, 10 and 11 have the function of binding hTfR. These combinations would amount to mutations in the CDRs when compared to those that have been disclosed in the specification as having the ability to bind to hTfR.
The state of the art/the level of predictability in the art
The state of the art teaches that with regards to changes in the amino acid residues on binding domains, it is especially important to disclose which residues are permissive to mutation. As discussed in the Non-Final Office Action, even minor changes in the amino acid sequences of the heavy and light variable regions, particularly in the CDRs, may dramatically affect antigen-binding function as evidenced by Rudikoff et al. (Proceedings of the National Academy of Sciences USA, Vol., 79, Pg. 1979-1983, 1982, see Abstract). Note that an enabling disclosure for the preparation and use of only a few analogs of a product does not enable all possible analogs where the characteristics of the analogs are unpredictable. See Amgen Inc. v. Chugai Pharmaceutical Co. Ltd. (18 USPQ 2d 1027 (CAFC 1991)).
Not knowing and absent further experimentation, which modifications can retain antigen binding function and which cannot, even a single change of an encoded amino acid can unpredictably affect structure and function, leads to one having no predictability or expectation of success for the function of any given antibody modification. Such random experimentation to identify at a later time what structure or fragment or modification is or is not functional and is embraced by Applicant’s claims is undue experimentation.
The quantity of experimentation needed to make or use the invention based on the content of the disclosure
Based on the instant disclosure and prior art, there is no known method through which one of ordinary skill in the art would have been able to reliably predict or otherwise envisage all possible mutations in the LCDR3, or mutations in any one of the HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3, that would retain the binding function to hTfR. Therefore, in order to practice the invention as claimed, one of ordinary skill in the art would have to perform undue experimentation to create and function test all possible anti-hTfR antibodies or antigen-binding fragments for retention of functional activity that binds hTfR.
The Examiner confirms that Applicant is enabled for anti-hTfR antibodies or antigen-binding fragments thereof that comprise the following combinations of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 SEQ ID NOs: (i) 26, 28, 7, 29, 10 and 11; (ii) 27, 28, 7, 29, 10 and 11; (iii) 5, 28, 7, 29, 10 and 11; (vii) 26, 28, 7, 9, 10 and 11; (viii) 26, 27, 7, 9, 10 and 11; (ix) 5, 28, 7, 9, 10 and 11; and (xii) 5, 6, 7, 9, 10 and 11.
Conclusion
In view of the Wands factors as discussed above, one of ordinary skill in the art would have to engage in undue experimentation to practice the full scope of the instant claimed invention. This is because the art teaches that it is unpredictable whether or not CDR variants of known antibodies or binding domains will function as such, and the specification does not provide direction on which constructs below 100% identity have function, or do not have function, as claimed in order to perform the method as claimed. In other words, the specification does nothing to ameliorate these concerns over the breadth of the claims rejected above with respect to functional variants, therefore, one would be burdened with undue experimentation to make or use the products of instant claims as broadly as they are currently claimed.
Enablement can be met by amending claim 35 to remove part a) which does not recite amino acid sequence for LCDR3; and reciting only the combinations of HCDR1, HCDR2, HCDR3, LCDR1, LCDR2 and LCDR3 comprising SEQ ID NOs: of: (i) 26, 28, 7, 29, 10 and 11; (ii) 27, 28, 7, 29, 10 and 11; (iii) 5, 28, 7, 29, 10 and 11; (vii) 26, 28, 7, 9, 10 and 11; (viii) 26, 27, 7, 9, 10 and 11; (ix) 5, 28, 7, 9, 10 and 11; and (xii) 5, 6, 7, 9, 10 and 11 that the specification discloses are capable of binding to hTfR.
Claim Rejections - 35 USC § 102
The following is a quotation of the appropriate paragraphs of 35 U.S.C. 102 that form the basis for the rejections under this section made in this Office action:
A person shall be entitled to a patent unless –
(a)(1) the claimed invention was patented, described in a printed publication, or in public use, on sale, or otherwise available to the public before the effective filing date of the claimed invention.
Claims 45, 56 and 57 are rejected under 35 U.S.C. 102(a)(1) as being clearly anticipated by Sonoda et al. (Molecular Therapy Volume 26, Issue 5, 2 May 2018, Pages 1366-1374).
Sonoda et al. teaches a fusion protein which is able to penetrate the blood-brain-barrier called JR-141, which consists of an anti-human transferrin receptor (hTfR) antibody and intact human iduronate-2-sulfatase (hIDS) (Abstract). They teach that IDF is an enzyme that catalyzes the degradation of glycosaminoglycans (GAGs), and that a deficiency of IDF leads to accumulation of GAGs in most cells in all tissues and organs, resulting in severe somatic and neurological disorders (Abstract). They also teach in Figure 1A, the schematic representation of JF-141, comprising of a heavy chain, a light chain, an Fc polypeptide and the human IDS enzyme (Figure 1A). They further teach a cDNA consisting of hIDS and humanized anti-human TfR antibody used to produce JR-141 (Pg 1370 and 1371 Section titled “Preparation of humanized anti-hTfR antibody-fused hIDS protein, JR-141”). Even further, they teach intravenous administration of JR-141 to mice or monkeys for treating animal models of Mucopolysaccharidosis II (MPS II), an X-linked recessive lysosomal storage disease caused by mutations in the iduronate-2-sulfatase (IDS) gene (Abstract).
Therefore, Sonoda et al. anticipates instant claims 45, 56 and 57.
Allowable Subject Matter
The anti-human transferrin receptor (hTfR) antibody or an antigen- binding fragment thereof, wherein the antibody or antigen-binding fragment comprises:
a HCDR1 comprising GYTFTRYY (SEQ ID NO: 26), an HCDR2 comprising IDPSVSET (SEQ ID NO: 28), an HCDR3 comprising SQIRLPYYYAMDS (SEQ ID NO: 7), a LCDR1 comprising QDISSF (SEQ ID NO: 29), an LCDR2 comprising YTS (SEQ ID NO: 10) and an LCDR3 comprising QQGNTLPRT (SEQ ID NO: 11);
a HCDR1 comprising GYTFTRYW (SEQ ID NO: 27), an HCDR2 comprising IDPSVSET (SEQ ID NO: 28), an HCDR3 comprising SQIRLPYYYAMDS (SEQ ID NO: 7), a LCDR1 comprising QDISSF (SEQ ID NO: 29), an LCDR2 comprising YTS (SEQ ID NO: 10) and an LCDR3 comprising QQGNTLPRT (SEQ ID NO: 11);
a HCDR1 comprising DYTFTRYW (SEQ ID NO: 5), an HCDR2 comprising IDPSVSET (SEQ ID NO: 28), an HCDR3 comprising SQIRLPYYYAMDS (SEQ ID NO: 7), a LCDR1 comprising QDISSF (SEQ ID NO: 29), an LCDR2 comprising YTS (SEQ ID NO: 10) and an LCDR3 comprising QQGNTLPRT (SEQ ID NO: 11);
a HCDR1 comprising GYTFTRYY (SEQ ID NO: 26), an HCDR2 comprising IDPSVSET (SEQ ID NO: 28), an HCDR3 comprising SQIRLPYYYAMDS (SEQ ID NO: 7), a LCDR1 comprising QDINSF (SEQ ID NO: 9), an LCDR2 comprising YTS (SEQ ID NO: 10) and an LCDR3 comprising QQGNTLPRT (SEQ ID NO: 11);
a HCDR1 comprising GYTFTRYW (SEQ ID NO: 27), an HCDR2 comprising IDPSVSET (SEQ ID NO: 28), an HCDR3 comprising SQIRLPYYYAMDS (SEQ ID NO: 7), a LCDR1 comprising QDINSF (SEQ ID NO: 9), an LCDR2 comprising YTS (SEQ ID NO: 10) and an LCDR3 comprising QQGNTLPRT (SEQ ID NO: 11);
a HCDR1 comprising DYTFTRYW (SEQ ID NO: 5), an HCDR2 comprising IDPSVSET (SEQ ID NO: 28), an HCDR3 comprising SQIRLPYYYAMDS (SEQ ID NO: 7), a LCDR1 comprising QDINSF (SEQ ID NO: 9), an LCDR2 comprising YTS (SEQ ID NO: 10) and an LCDR3 comprising QQGNTLPRT (SEQ ID NO: 11); and
a HCDR1 comprising DYTFTRYW (SEQ ID NO: 5), an HCDR2 comprising IDPSVSEC (SEQ ID NO: 6), an HCDR3 comprising SQIRLPYYYAMDS (SEQ ID NO: 7), a LCDR1 comprising QDINSF (SEQ ID NO: 9), an LCDR2 comprising YTS (SEQ ID NO: 10) and an LCDR3 comprising QQGNTLPRT (SEQ ID NO: 11), are free of prior art.
The anti-human transferrin receptor (hTfR) antibody or an antigen-binding fragment thereof comprising a) a heavy chain comprising SEQ ID NO: 32 and a light chain comprising SEQ ID NO: 31; b) a heavy chain comprising SEQ ID NO: 30 and a light chain comprising SEQ ID NO: 31; and c) a heavy chain comprising SEQ ID NO: 33, a light chain comprising SEQ ID NO:31, and an Fc polypeptide comprising SEQ ID NO: 34, are free of prior art.
Conclusion
No claims are allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to Yie-Chia Lee (Tonya) whose telephone number is (571)272-0123. The examiner can normally be reached Monday - Friday 7.30a - 3.30p Eastern Time Zone.
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/YIE-CHIA LEE (TONYA)/Examiner, Art Unit 1642
/SEAN E AEDER/Primary Examiner, Art Unit 1642
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