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 .
Applicant’s response and amendments received December 19, 2025 are acknowledged.
Claims 10, 13, 17, 18, 21, 23-25, 27, and 30-33 have been canceled.
Claims 1-9, 11, 12, 14-16, 19, 20, 22, 26, 28, and 29 are pending in the instant application.
Claim 1 is independent.
Applicant’s election of the invention of group I, drawn to polypeptides that bind alpha 1 antitrypsin, and the polypeptide species of SEQ ID NO:1 (AAHFHK) in the reply filed on December 19, 2025 is acknowledged. Because applicant did not distinctly and specifically point out the supposed errors in the restriction requirement, the election has been treated as an election without traverse (MPEP § 818.01(a)).
Claims 11, 12, and 29 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species or inventions, there being no allowable generic or linking claim. Election was made without traverse in the reply filed on December 19, 2025 as discussed above.
Claims 1-9, 14-16, 19, 20, 22, 26, and 28 are under examination in this office action as they read on the species of AAHFHK/SEQ ID NO:1.
Information Disclosure Statement
The IDS form received 3/7/2023 is acknowledged and the references cited therein have been considered.
Specification
The specification is objected to because Figure 2 discloses biological sequences longer than 4 residues which are not accompanies by SEQ ID number in either the figure itself or in its brief description (i.e. paragraph [023]). It should be noted that the sequences present in Figure 2 appear to be disclosed elsewhere in the specification accompanied by SEQ ID numbers and thus editing the description of Figure 2 to include appropriate SEQ ID numbers is the simplest solution to obviate this problem although other remedies are possible.
Additionally, the legends for Figures 3, 7, 10 discuss colors including red, blue, etc. yet the figures are all in black and white or greyscale, and no petition to accept colored drawings appears to be present in the instant application. Inspection of the figures in question does not reveal an immediate need for the conveyed information to be set forth in color. Thus, removal of refences to colors which are not present in the drawings is very strongly suggested. Alternatively, applicant may submit colored versions of the figures in question along with a petition to accept colored drawings and persuasive arguments as to why the presence of color is critically necessary.
Claim Objections
Claims 7 and 8 are objected to for the following reasons:
In claim 7, applicant recites that the claimed peptide has “at least 90% sequence identity” to any one of SEQ ID numbers 1-23, with claim 8 simply limiting the sequences to any one of SEQ ID NOs:1-7. The smallest possible peptide that can be ≥ 90% identical to a reference sequence without being 100% identical is 10 amino acid residues (i.e. 9 matches and one mismatch/mutation, 9/10 = 90%). As evidenced by Table 3 in paragraph [097] of the instant specification, all of SEQ ID NOs:1-23 are either 6 or 8 amino acid residues in length. Thus, none of these sequences can be mutated while meeting the ≥ 90% identical limitation required by the claims. As such there is no reason why these claim recite percent identity limitations as no mutations to the sequences represented by the SEQ ID numbers are possible. Appropriate correction is required.
Claim Rejections - 35 USC § 112
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 9 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.
In claim 8, applicant recites that the claimed peptide has “at least 90% sequence identity” to any one of SEQ ID numbers 1-7. However, all of SEQ ID NOs:1-7 are either 6 or 8 residues in length. As such, no mutations to the recited SEQ ID numbers are possible if the resulting sequence must be ≥ 90% identical to the reference sequence. Thus claim 8 properly should read “The peptide ligand of claim 1, wherein the peptide ligand comprises at least 6 amino acids and comprises the amino acid sequence of any one of SEQ ID NOs: 1-7.” Claim 9 depends from claim 8 and recites that the claimed peptide comprises either (i) one of SEQ ID NOs:1-5 or (ii) one of SEQ ID NO:6 or 7. Given that the percent identity “limitations” of claim 8 permit no mutations, there is no actual change to the claimed product (i.e. claimed polypeptide sequence) when comparing claim 8 and its dependent claim 9. Since claim 9 adds no additional limitations, it is not properly dependent.
Applicant may cancel the claim, amend the claim to place the claim in proper dependent form, rewrite the claim in independent form, or present a sufficient showing that the dependent claim complies with the statutory requirements.
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 1-6, 14-16, 19, 20, 22, 26, and 28 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.
Applicant has broadly claimed polypeptides which are minimally 6 amino acid residues in length which comprise the functional property of binding to alpha 1 antitrypsin (AAT). Independent claim 1 indicates a handful of residue types which must be present, such as histidine or lysine, but places no constrains on how such residues are arranged. Notably, as presently constructed claim 1 requires the 6mer peptide to have one residue from each of (i)-(iii) in any order, specifically (i) H or K, (ii) N or S, and (iii) F or W with the other three residues being potentially anything. Dependent claims recite additional functional properties such as the characteristics of the binding epitopes within AAT (claim 4), how much AAT can be bound by the polypeptide (claims 5 and 6) or intended uses for such polypeptides such as purifying AAT from various liquid feedstocks (claims 19, 20, 22, and 26). Additionally, other dependent claims specify sequences of at least 6 amino acids by SEQ ID number that must be present in the claimed polypeptides (claims 7-9). To support such claims, applicant discloses working examples wherein peptides 23 peptides which are 6 or 8 residues in length were tested for binding to AAT, including when coupled to beads via a G or GSG linker sequence (see particularly Tables 3-6).
The guidelines for the Examination of Patent Applications Under the 35 U.S.C. 112, § 1 "Written Description" Requirement make clear that if a claimed genus does not show actual reduction to practice for a representative number of species, then the Requirement may be alternatively met by reduction to drawings, or by disclosure of relevant, identifying characteristics, i.e., structure or other physical and or chemical properties, by functional characteristics coupled with a known or disclosed correlation between function and structure, or by a combination of such identifying characteristics, sufficient to show the applicant was in possession of the genus. See MPEP 2163. In The Regents of the University of California v. Eli Lilly (43 USPQ2d 1398-1412) 19 F. 3d 1559, the court held that disclosure of a single member of a genus (rat insulin) did not provide adequate written support for the claimed genus (all mammalian insulins). In this same case, the court also noted: “A definition by function, as we have previously indicated, does not suffice to define the genus because it is only an indication of what the gene does, rather than what it is. See Fiers, 984 F.2d at 1169-71, 25 USPQ2d at 1605-06 (discussing Amgen). It is only a definition of a useful result rather than a definition of what achieves that result. Many such genes may achieve that result. The description requirement of the patent statute 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."). Accordingly, naming a type of material generally known to exist, in the absence of knowledge as to what that material consists of, is not a description of that material.” The court has further stated that “Adequate written description requires a precise definition, such as by structure, formula, chemical name or physical properties, not a mere wish or plan for obtaining the claimed chemical invention.” Id. at 1566, 43 USPQ2d at 1404 (quoting Fiers, 984 F.2d at 1171, 25 USPQ2d at 1606). Also see Enzo-Biochem v. Gen-Probe 01-1230 (CAFC 2002). Recent court cases have emphasized the need for correlation between a well-defined structure and recited functional limitations. For example, the courts have indicated that recitation of an antibody which has specific functional properties in the absence of knowledge of the antibody sequences that give rise to said functional properties do not satisfy the requirements for written description. See for example AbbVie Deutschland GmbH v. Janssen Biotech. Inc. 759 F.3d 1285 (Fed. Cir. 2014) as well as Amgen v. Sanofi, (Fed Cir, 2017-1480. 10/5/2017). Applicant is reminded that the courts have long ruled that “Possession may not be shown by merely describing how to obtain possession of members of the claimed genus or how to identify their common structural features.” See University of Rochester, 358 F.3d at 927, 69 USPQ2d at 1895. As such, disclosure of a screening assay to test for functional properties of a polypeptide (such binding to AAT) does not provide evidence of possession of the polypeptide itself.
As discussed above, applicant made and tested 23 peptides for binding to AAT, either alone or via a G or GSG linker when conjugated to a solid support such as a resin bead. The claimed polypeptides are significantly broader in scope with most claims simply indicating that some particular amino acids amino acids should be present with no rhyme or reason as to how such residues are arranged within the longer claimed polypeptide structure. However, it is very well known that the sequence of a polypeptide (i.e. its structure) dictates its functional properties, and that even minor structural differences among structurally related compounds or compositions can result in substantially different biology, expression and activities. It is known in the art that many amino acid residues alter secondary structure, such as proline which often forms kinks in secondary structure, while residues like cysteine and methionine can be involved in disulfide bond formation (Stryer, see entire selection). Other residues can introduce either positive or negative charge to disrupt electrostatic interactions, or alter hydrophobicity or steric packing (ibid). Note that the minimum size of the claimed polypeptide is 6 residues, yet claim 1 indicates possible alternatives for only 3 of the positions and does not indicate where such residues occur within the larger peptide (for example claim 2 requires an alanine to be present, but it could be at position 1, 2, 3, 4, 5, 6, or somewhere else per the claim as six residues is the minimum size but no maximum size is recited). Further, Attwood (Science 2000; 290:471-473) teaches that “[i]t is presumptuous to make functional assignments merely on the basis of some degree of similarity between sequences (such as a given percent identity) while Skolnick et al. (Trends in Biotech., 18(1): 3439, 2000) teach that the skilled artisan is well aware that assigning functional activities for any particular protein or protein family based upon sequence homology is inaccurate, in part because of the multifunctional nature of proteins (e.g., "Abstract" and "Sequence based approaches to function prediction", page 34). Even in situations where there is some confidence of a similar overall structure between two proteins, only experimental research can confirm the artisan's best guess as to the function of the structurally related protein (see in particular "Abstract" and Box 2). Thus, in the absence of experimental data, artisans would not reasonably expect the vast genus of peptides encompassed by the independent claim and those dependent therefrom apart from claims 7-9 to have the functional property of binding AAT as there does not appear to be any conserved structure/sequence that when present in the peptide necessarily results in AAT binding activity that is set forth in the instant specification. It should also be pointed out that while claims 7 and 8 appear to recite percent identity mutations and thus allow for mutations, the length of the SEQ ID numbers is so short and the identity so high that no mutations are actually possible as discussed more thoroughly earlier in this office action.
Therefore, while artisans would reasonably accept that applicant was in possession of the polypeptides of SEQ ID NO:1-23 as well as extended versions of said polypeptides comprising G of GSG linker sequences, any or all of which may be present on a solid support such as a chromatography bead, artisans would not reasonably believe that applicant has in possession of the breath of incompletely defined polypeptide sequences which necessarily have the function of binding AAT. Logically, if applicant is not in possession of the full extent of the claimed polypeptides, applicant is also not in possession of products such as resins and other solid surfaces which comprise such polypeptides.
Claim Rejections - 35 USC § 102
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 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.
(a)(2) the claimed invention was described in a patent issued under section 151, or in an application for patent published or deemed published under section 122(b), in which the patent or application, as the case may be, names another inventor and was effectively filed before the effective filing date of the claimed invention.
Claims 1-3, 14, 16, 19, 20, 22, 26, and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Grebe (WO 2012/038820).
Grebe teaches multiple antibodies that bind human alpha 1 antitrypsin and their coupling to solid supports for use in immunochromatography devices (see entire document, particularly the abstract, background, Figure 3, example 1, and the claims). It should be noted that antibodies are longer than 6 amino acid residues and comprise all 20 standard amino acids, including lysine, serine, phenylalanine, and alanine. Further, while paragraph [037] of the instant specification states that generally the difference between “peptide” and “polypeptide" is based upon size, and exemplifies the cutoff by teaching that “The term "peptide" typically refers to short amino acid polymers (e.g., chains having fewer than 25 amino acids), whereas the term "polypeptide" typically refers to longer amino acid polymers (e.g., chains having more than 25 amino acids).” Note that “typically” does not define or require peptides to always be 25 residues or smaller, and thus such exemplification is not limiting. As such the recitation of “peptide” does not disqualify antibodies as there is no explicit upper bound for polypeptide size recited in any of the instant claims and as discussed supra a limiting definition of “peptide” is not disclosed in the instant specification. It should be noted that the antibodies of Grebe are taught as being used in lateral flow chromatography strips, and thus they clearly bind to AAT when present in a fluid, such as human blood and plasma as in his working examples. However, recitations as to they type of fluid that can be contacted to the composition, such as CHO tissue culture supernatant or yeast hydrolysate, in no way alters the structure of that which is claimed, which is specifically a polypeptide longer than 6 residues that binds AAT and is bound to a solid support. Thus such recitations are best interpreted as “intended use” limitations, and therefore do not provide patentable distinctiveness unless they necessarily alter the structure of what is presently claimed to be different from that of the prior art . See also MPEP 211.02. Therefore, the prior art anticipates that which is presently claimed.
Claims 1-9, 14-16, 19, 20, 22, 26, and 28 are rejected under 35 U.S.C. 102(a)(1) as being anticipated by Chu et al. (J Chromatogr A, available online 22 July 2022).
Chu et al. disclose conjugating peptides to Toyopearl beads for use in affinity purifying alpha 1 antitrypsin for CHO tissue culture media (see entire document, particularly the abstract and conclusions). Such affinity ligand peptides include AAHFHK-GSG which is more than 6 amino acids in total length and comprises the elected species of SEQ ID NO:1 (see most particularly the left column of page 4 as well as Tables 3 and S2 of Chu et al). Notably the affinity ligand peptides of Chu et al. were initially identified using a binding site analysis which included a GRAVY index (see most particularly section 3.1, Tailoring a peptide library focused to the discovery of AAT-binding peptides) followed by in silico and web lab binding studies to confirm high binding activity of Aat from CHO supernatants (see particularly sections 3.3-3.5). It is noted that while Chu et al. disclose recovery of recombinant Aat from CHO cells they do not teach purification from yeast cells as recited in instant claim 26. However, all claims under examination are for products, specifically polypeptides that bind AAT either free in solution or attached to a solid support such as resin beads. Thus, reciting that such a composition is to be used to purify material from yeast cells is a statement of intended use, and such a limitation does not provide patentable distinctiveness unless it physically alters the claimed product to be something different from that previously disclosed in the art. See also MPEP 2111.02. In the instant case recitation of recombinant feedstock sources do not alter the physical structure of the claimed composition in any way. As such the prior art teaches that which is presently claimed.
No claims are allowable.
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Michael Szperka
Primary Examiner
Art Unit 1641
/MICHAEL SZPERKA/Primary Examiner, Art Unit 1641