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 .
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.
Status of Claims
Claims 1-12 are pending. Claims 5-12 are withdrawn. Claims 1-4 are pending and under examination.
Election/Restrictions
Applicant’s election without traverse of Group I (claims 1-4) in the reply filed on 09/21/2026 is acknowledged.
Claims 5-12 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to nonelected inventions, there being no allowable generic or linking claim. Election was made without traverse.
Claim Objections
Claims 1 and 4 are objected to because of the following informalities:
Claim 1, because the abbreviation of TSHR is used without the claim, after thyroid-stimulating hormone receptor, the claim should incorporate – (TSHR) –.
Claim 4 recites “the N-terminus thereof” should be – the N-terminus of the extracellular segment of TSHR protein –. This way it is consistent with the structure of the amended claim 1. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 1-4 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 applications subject to pre-AIA 35 U.S.C. 112, the inventor(s), at the time the application was filed, had possession of the claimed invention. This is a new matter rejection.
Applicant has amended the claims filed 09/21/2026 to recite “A recombinant thyroid-stimulating hormone receptor protein consisting of” (emphasis added) is new matter. Applicants have not provided passages or sequences of the instant specification to support the amendment. In particular, the examiner is not able to find support, for example, SEQ ID NO:12 is directly connected to the N-terminus of SEQ ID NO: 13 (see claim 2). Even though SEQ ID NO: 11 encompasses SEQ ID NOs: 12-13, it does not consist only SEQ ID NOs: 12-13.
For the reasons stated above, the specification fails to provide direction or blaze marks to limitations the recombinant thyroid-stimulating hormone receptor protein consisting of an extracellular segment of TSHR protein and an intracellular segment of TSHR protein, wherein the C-terminus of the extracellular segment of TSHR protein is connected to the N-terminus of the intracellular segment of TSHR protein.
Claims 1-4 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.
The MPEP lists factors that can be used to determine if sufficient evidence of possession has been furnished in the disclosure of an application. These include “level of skill and knowledge in the art, partial structure, physical and/or chemical properties, functional characteristics alone or coupled with a known or disclosed correlation between structure and function, and the method of making the claimed invention. Disclosure of any combination of such identifying characteristics that distinguish the claimed invention from other materials and would lead one of skill in the art to the conclusion that the applicant was in possession of the claimed species is sufficient.” MPEP § 2163. While all of the factors have been considered, a sufficient amount for a prima facie case are discussed below.
Further, to provide evidence of possession of a claimed genus, the specification must provide sufficient distinguishing identifying characteristics of the genus. The factors to be considered include: a) the scope of the invention; b) actual reduction to practice; c) disclosure of drawings or structural chemical formulas; d) relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation; e) method of making the claimed compounds; f) level of skill and knowledge in the art; and g) predictability in the art.
Scope of the invention
The claims are drawn to a recombinant thyroid-stimulating hormone receptor protein, consisting of an extracellular segment of TSHR protein and an intracellular segment of TSHR protein, wherein the C-terminus of the extracellular segment of TSHR protein is connected to the N-terminus of the intracellular segment of TSHR protein.
The claims as a whole cover a genus of segments of TSHR proteins as a thyroid stimulating hormone receptor protein. Explicit in the claims is that such combination of segments (i.e., peptides) would possess certain functional characteristics; namely, the ability to conjugate to TSH as a receptor protein.
Disclosure of drawings or structural chemical formulas/ Actual Reduction to Practice
The specification only discloses SEQ ID NO: 11 to represent the recombinant thyroid-stimulating hormone receptor protein. Meanwhile, the specification does not provide evidence that SEQ ID NO: 12 is directly connected to the N-terminus of SEQ ID NO: 13 to form a recombinant thyroid-stimulating hormone receptor protein as claimed.
Relevant identifying characteristics including complete structure, partial structure, physical and/or chemical properties, and structure/function correlation
A skilled artisan cannot, as one can do with a fully described genus, visualize or recognize the identity of the members of the genus that would exhibit this functional property. The structural features common to the members of the genus are unknown in a wide range of sequences.
A single disclosed species would not put one skilled in the art in possession of a protein that consists of extracellular segment of TSHR protein and an intracellular segment of TSHR protein, wherein the C-terminus of the extracellular segment of TSHR protein is connected to the N-terminus of the intracellular segment of TSHR protein to have claimed functional characteristics (i.e., receptor protein for thyroid-stimulating hormone).
As evidence, see Lloyd et al. ("Modelling the human immune response: performance of a 10e11 human antibody repertoire against a broad panel of therapeutically relevant antigens", Protein Engineering, Design and Selection, Volume 22, Issue 3, 1 March 2009, Pages 159–168), which shows how a repertoire of 1x1011 human antibody variable regions can generate large numbers of unique, biologically active scFvs against a variety of polypeptide targets (see e.g., at page 161-62 bridging paragraph, in Table 1 and Figs. 1-2).
As further illustration of the unpredictability in the art, Brown et al. (“Tolerance of single, but not multiple, amino acid replacements in antibody VH CDR 2: a means of minimizing B cell wastage from somatic hypermutation?”, J Immunol. 1996 May;156(9):3285-91), describes how a one amino acid change in the VHCDR2 of a particular antibody was tolerated whereas, the antibody lost binding upon introduction of two amino changes in the same region (at 3290 and Tables 1 and 2).
In view of the above, one cannot visualize or recognize the identities of the members of the genus based from the disclosure of SEQ ID NO: 11. Although Applicants disclose reduction to practice to a full-length sequence, given the unpredictability of making changes to protein structures while preserving binding function as above, one cannot envision the structures of those proteins falling within the claimed genuses.
A claimed invention may not be adequately described where an invention is described solely in terms of function and there is no described or art recognized correlation or relationship between the structure of the invention and its function. A biomolecule defined solely by its ability to perform a function, such as recognizing a construct, without a known or disclosed correlation between that function and the structure of the sequence, normally is not a sufficient identifying characteristic for written description purposes.
In this case, the disclosure of merely a single sequence for the claimed functional properties. For example, Applicant does not even provide evidence that a receptor protein of only SEQ ID NO:12 connected to SEQ ID NO: 13 would produce the claimed functional characteristics. The common structural features that give rise to the desired functional properties are unknown in other sequences.
The description requirement of the patent statue requires a description of an invention, not an indication of a result that one might achieve if one made that invention. See In re Wilder, 736, F.2d 1516, 1521, 222 USPQ 369, 372-73 (Fed. Cir. 1984) (affirming rejection because the specification does “little more than outlin[e] goals appellants hope the claimed invention achieves and the problems the invention will hopefully ameliorate.”).
In summary, the specification fails to provide adequate written description for the genus of any claimed segments of TSHR protein. In particular, the specification discloses a specific sequence that as the thyroid-stimulating hormone receptor protein. Therefore, the specification does not reasonably convey to one skilled in the relevant art that the inventor(s), at the time the application was filed, had possession of the claimed invention.
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.
Claims 3-4 are ejected 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.
With respect to claim 3, because claim 1 recites “a recombinant thyroid-stimulating hormone receptor protein, consisting of ” an extracellular segment and an intracellular segment, the recitation of “the N-terminus thereof is connected to an exogeneous secretion signal peptide” does not further limit the claimed TSHR protein. The addition of another molecule at the N-terminal does not limit the structure that consists of just the extracellular segment and the intracellular segment.
With respect to claim 4, because claim 1 recites “a recombinant thyroid-stimulating hormone receptor protein, consisting of ” an extracellular segment and an intracellular segment, the recitation of “the C-terminus of the intracellular segment of TSHR protein is further connected to a purification tag sequence” does not further limit the claimed TSHR protein. The addition of another molecule at the C-terminal does not limit the structure that consists of just the extracellular segment and the intracellular segment.
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 § 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 1 and 3-4 are rejected under 35 U.S.C. 102(1) as being anticipated by Sanders et al. (US8097699B2, published 01/17/2012, Application No. 11/896,073).
Sanders teaches composition comprising a TSHR polypeptide (abstract). Sanders teaches a crystallizable composition a TSHR polypeptide that is to say a polypeptide comprising contiguous amino acids from the primary sequence of a thyroid stimulating hormone receptor (at col. 3, lines 12-17). Sanders further teaches a complex is advantageous in that the TSHR-binding entity may stabilize the TSHR polypeptide and producing crystallizable complexes comprising a TSHR polypeptide and a TSHR-binding entity in which the TSHR-binding entity has a relatively high affinity for the TSHR polypeptide (at col. 3, lines 22-30). Sanders teaches SEQ ID NO: 20, which encompasses SEQ ID NO: 12 and SEQ ID NO: 13 (i.e., SEQ ID NO: 11 of instant disclosure). The sequence alignment (below) shows that Sander’s SEQ ID NO: 20 has 100% query match to the claimed SEQ ID NO: 12 and SEQ ID NO: 13.
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With respect to claims 3-4, because claim 1 recites a recombinant thyroid-stimulating hormone receptor protein consisting of, the limitations of wherein the N-terminus thereof is connected to an exogenous secretion signal peptide (claim 3) and wherein the C-terminus of the intracellular segment of TSHR protein is further connected to a purification tag sequence (claim 4) are directed to intended use. Because Sanders teach the claimed recombinant thyroid-stimulating hormone receptor protein, the structure of Sander would be capable of performing the intended use.
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 1-4 are rejected under 35 U.S.C. 103 as being unpatentable over Sanders et al. (US8097699B2, published 01/17/2012, Application No. 11/896,073).
Sanders has been discussed in the above rejection. Although Sanders’ SEQ ID NO: 20 has the claimed SEQ ID NO:12 and SEQ ID NO:13, the reference does not exclusively teach the amino acid sequence of the extracellular segment of TSHR protein is set forth in SEQ ID NO: 12, and the amino acid sequence of the intracellular segment of TSHR protein is set forth in SEQ ID NO:13 and the C-terminus of SEQ ID NO: 12 is connected to the N-terminus of SEQ ID NO: 13.
However, it would have been obvious to have identified specific regions of SEQ ID NO: 20 as taught by Sanders, which encompasses the instant claimed SEQ ID NOs: 12-13, because Sanders teaches producing crystallizable complexes comprising a TSHR polypeptide and a TSHR-binding entity in which the TSHR-binding entity has a relatively high affinity for the TSHR polypeptide. Thus, it would have been obvious to have identified and extrapolated specific amino acid regions associated with SEQ ID NO: 20 for specific binding affinity.
With respect to claims 3-4, because claim 1 recites a recombinant thyroid-stimulating hormone receptor protein consisting of, the limitations of wherein the N-terminus thereof is connected to an exogenous secretion signal peptide (claim 3) and wherein the C-terminus of the intracellular segment of TSHR protein is further connected to a purification tag sequence (claim 4) are directed to intended use. Because Sanders teach the claimed recombinant thyroid-stimulating hormone receptor protein, the structure of Sander would be capable of performing the intended use.
Conclusion
No claim is allowed.
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/N.P.N/Examiner, Art Unit 1678
/SHAFIQUL HAQ/Primary Examiner, Art Unit 1678
