DETAILED ACTION
Notice of Pre-AIA or AIA Status
1. The present application, filed on or after March 16, 2013, is being examined under the first inventor to file provisions of the AIA .
2. The Preliminary Amendment filed on June 21, 2023 and October 13, 2025, have has been received and entered.
3. Applicant’s election with traverse of Group I (claims 1-7 with SEQ ID NO: 3) on November 28, 2025, is acknowledged. The traversal is on the grounds that claim 12 should be joined to group I instead of group II. Applicant state that claim 12 has all the limitations of claim 1 except that it merely adds an insoluble carrier to which the polypeptide. This argument is not persuasive. Claim 1 is a product claim directed to the polypeptide and claim 12 can be viewed as a device or apparatus (another product). The method of claim 13 uses said device/apparatus and thus claim 12 is grouped appropriately with the method. The device provides ease for the method but is not needed for the product which operates structurally and functionally separate from the device. Further under PCT Rules 13.1 applicant is entitled to the first product and method of making and using the same, and claim 12 can be construed as a second product. The two groups were deemed as lacking unity of invention based on art as well. Thus, the Lack of Unity of record is proper and is final.
Claim Disposition
4. Claims 8-11 are cancelled. Claims 1-7 and 12-14 are pending. Claims 1-7 are under examination. Claims 12-14 are withdrawn from consideration as directed to a non-elected invention.
Information Disclosure Statement
5. The Information Disclosure Statements filed on June 21, 2023 and December 12, 2024, have been received and entered. The references cited on the PTO-1449 Form have been considered by the examiner and a copy is attached to the instant Office action.
Drawing
6. The drawings filed on June 21, 2023, have been accepted by the examiner.
Abstract
7. The abstract is objected to for the following informalities:
Applicant is reminded of the proper content of an abstract of the disclosure.
A patent abstract is a concise statement of the technical disclosure of the patent and should include that which is new in the art to which the invention pertains. The abstract should not refer to purported merits or speculative applications of the invention and should not compare the invention with the prior art.
If the patent is of a basic nature, the entire technical disclosure may be new in the art, and the abstract should be directed to the entire disclosure. If the patent is in the nature of an improvement in an old apparatus, process, product, or composition, the abstract should include the technical disclosure of the improvement. The abstract should also mention by way of example any preferred modifications or alternatives.
Where applicable, the abstract should include the following: (1) if a machine or apparatus, its organization and operation; (2) if an article, its method of making; (3) if a chemical compound, its identity and use; (4) if a mixture, its ingredients; (5) if a process, the steps.
Extensive mechanical and design details of an apparatus should not be included in the abstract. The abstract should be in narrative form and generally limited to a single paragraph within the range of 50 to 150 words in length.
See MPEP § 608.01(b) for guidelines for the preparation of patent abstracts.
The following is suggested to be clear and concise:
“[[An object of the present invention is to provide a polypeptide having excellent
alkaline stability and also allowing an immunoglobulin or a fragment thereof that has been]] The present invention provides an alkaline stable polypeptide that allows an immunoglobulin or fragment thereof bound to be eluted in a [[weakly]] weak acidic range, by [[modifying an amino acid sequence of an immunoglobulin-binding domain of Protein A. By]] substitution of serine at position 41 with an amino acid with a hydrophobic side chain, tyrosine, or histidine in each immunoglobulin-binding domain of Protein A[[,]]. To obtain a polypeptide [[is obtained having]] with avidity for an immunoglobulin or a polypeptide containing an Fc region thereof, having [[excellent]] alkaline stability, and also allowing the immunoglobulin or the polypeptide containing an Fc region thereof that has been bound to be efficiently eluted under [[weakly]] weak acidic [[mild]] conditions.
Specification Objection
8. The specification is objected to for the following informalities:
The specification is objected to because the priority information is missing from page 1.
The title of the invention is not descriptive. A new title is required that is clearly indicative of the invention to which the claims are directed. The following is suggested: "Immunoglobulin- Binding Polypeptides and Methods of using the same".
The specification is objected to because trademarks are disclosed and they are not capitalized. The use of the trademark such as SP-Sepharose Fast Flow, has been noted in this application (see page 45, for example). It should be capitalized wherever it appears and be accompanied by the generic terminology. Although the use of trademarks is permissible in patent applications, the proprietary nature of the marks should be respected and every effort made to prevent their use in any manner, which might adversely affect their validity as trademarks.
Appropriate correction is required.
Claim objection
9. Claims 1-7 are objected to for the following informalities:
For clarity and precision of claim language it is suggested that claim 1 (A) is amended to recite “…. having a [[modification meeting the following conditions (i) to (iv) introduced into an amino acid sequence as set forth in any of SEQ ID NOS: 1 to 15:]]
serine at position 41 that is substituted…..or histidine in any of the amino acid sequence of SEQ ID NOs: 1 to 15….”. See (ii) to (iv) of (A) and (B) to (C) with similar language. The dependent claims hereto are also included.
For clarity claim 1 (B) should be amended to delete “few amino acids”, because it is hard to ascertain the amount.
For clarity it is suggested that claims 2-7 are amended to delete “according to” and instead recite “of” (i.e., The polypeptide of claim 1…).
For clarity claim 5 should be amended to recite “SEQ ID NOs…”.
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.
10. Claims 1-7 are rejected under 35 U.S.C. 112(b) or 35 U.S.C. 112 (pre-AIA ), second paragraph, as being indefinite for failing to particularly point out and distinctly claim the subject matter which the inventor or a joint inventor (or for applications subject to pre-AIA 35 U.S.C. 112, the applicant), regards as the invention.
Claim 1 and the dependent claims hereto are indefinite for the recitation of “a few amino acids” because it is unclear how to quantify that, especially with 15 different sequences and the amount of variation (substitution, insertion etc.). Is a few 2, 19, or 30?
Claims 6 and 7 lack clarity because of the recitation of a specific amino acid position being modified and the language of ‘in the amino acid sequence’, because it is unclear which of the 1 to 15 amino acid sequence is referred to.
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.
11. Claim(s) 1-2 and 6 is/are rejected under 35 U.S.C. 102 (a)(1) as being anticipated by Pastor et al. (2007, of record in the application).
Pastor et al. discloses that the hydrophobic core of the B domain of Protein A was redesigned and mutants with high thermal stability were obtained by screening based on binding affinity with IgG; and that mutants were obtained by replacing the amino acid at position 44 (corresponding to position 41 in SEQ ID NO:1 to 15 of the present application) with phenylalanine or threonine (see in particular abstract; page 14924, left column, paragraph 2 to page 14930, right column; paragraph 2; Tables 1 and 2; figure 10). Moreover, the reference describes the amino acid sequence of a peptide named H1-H2-H3p2 as one of the above mentioned mutants (Table 2). Therefore, the amino acid sequence becomes a sequence wherein, the amino acid sequence represented by SEQ ID NO:7 of the present application, three amino acid residues are added at the N-terminal side, the amino acid residue at position 41 is replaced by Phe, and the amino acid residue at position 44 is replaced by Val. In this case, as also described in reference (see in particular, page 14929, right column, paragraph 2), because the replacement of the amino acid residue at position 47 (corresponding to position 44 in SEQ ID NO: 1 to 15 of the present application) in the mutant of the present reference is conserved, it is extremely likely that the substitution and addition of the amino acids to the terminus did not cause a decrease in stability or a decrease in IgG elution capability. Moreover, as set forth in the description of the present application (paragraph [0106]), the replacement of the serine residue at position 44 in the mutant of the present reference (corresponding to position 41 in SEQ ID NO: 41 in SQ ID NO:1 to 15 of the present application) with a hydrophobic residue leads to an increase in residual activity following an alkaline treatment and an increase in the elution rate under weakly acidic conditions. Therefore, the limitations of the claims are met by the reference.
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.
12. This application currently names joint inventors. In considering patentability of the claims the examiner presumes that the subject matter of the various claims was commonly owned as of the effective filing date of the claimed invention(s) absent any evidence to the contrary. Applicant is advised of the obligation under 37 CFR 1.56 to point out the inventor and effective filing dates of each claim that was not commonly owned as of the effective filing date of the later invention in order for the examiner to consider the applicability of 35 U.S.C. 102(b)(2)(C) for any potential 35 U.S.C. 102(a)(2) prior art against the later invention.
13. Claim(s) 1-7 is/are rejected under 35 U.S.C. 103 as being unpatentable over Pastor et al. (2007, of record in the application) in view of JP2016-523959 (record in the application), JP2013-256479 (of record in the application), WO2012/165544 (of record in the application) and JP2010-156687(of record in the application).
The teaching of the primary reference pertaining to claims 1-2 and 6 is above.
The primary reference does not per se teach a replacement of glutamine residue, however, the secondary reference teaches replacing the glutamine residue at position 9 of the B or C domain of Protein A with an amino acid residue such as alanine; and that the invention provides both a polypeptide multimer and a separation matrix (see in particular abstract; and claims). Further the tertiary reference teaches that the elution properties are excellent under weakly acidic conditions in mutants wherein the glutamic acid residue at position 15 of Protein A was replaced by a histidine residue; and that one to three units of the sequence of the Protein A mutant were joined together (see in particular, abstract, claims and paragraph [0107]). Moreover, the fourth reference discloses mutants of Protein A with decreased affinity in the acidic region and an antibody capture agent. The fourth reference also states that substitutions of the amino acid residues at positions 9, 15, 24, etc., were performed; that a preferred targeted position for mutation can be selected not only in the B domain but also in the D, A, C and Z domains; and that a tandem-type amino acid sequence increases the effectiveness of antibody binding affinity (see in particular abstract, paragraphs [0031-0032], [0042-0043]; examples). Additionally, the fifth reference describes mutants wherein substitutions were performed at position 24 of the E, D, A, B, C and Z domains of Protein A, and an alkaline stable ligand comprising two or more domains (see in particular, claims and Table 1).
The primary reference does not describe a mutant in a domain other than the B domain of Protein A, but as described in the secondary and fourth/fifth references, for example, it was common technical knowledge before the effective date of the present application that a mutation site in a certain domain of Protein A can be selected as a mutation site in an different domain, and therefore a person skilled in the art could have easily prepared the same kind of mutant in a domain other than the B domain based on common technical knowledge available before the effective date of the present application, claim 1 is deemed obvious. Regarding claim 2 it does not create any new difference and claim 3 increases binding affinity (as also seen in the second to fifth references) to an antibody by joining multiple domains of Protein A together was widely known before the effective date of the present application, a person skilled in the art could have easily obtain a multiple-domain peptide in the invention described in primary reference based on the technique that was widely known before the priority date of the present application. Further claim 4, 5 and 7 are obvious although the primary reference does not describe performing the amino acid substitutions stipulated in these claims. It is clear, however, that applying the Protein A mutants described in the primary reference, which were obtained as mutants with excellent thermal stability, to antibody purification, which is a widespread use of Protein A, and then inserting additional mutations to suit the desired properties during antibody purification is an obvious problems for persons skilled in the art. Furthermore, as properties and the mutation sites that impart said properties, it would not have been particularly difficult for a person skilled in the art to choose properties such as the alkaline stability and the dissolution properties under acidic conditions described in the second to fifth references as well as the mutation sites that impart these properties. Regarding claim 6 it does not create any new difference.
Therefore, it would have been obvious for one of ordinary skill in the art before the effective filing date of the claimed invention to arrive at the claimed invention as a whole because the combined teaching of the references renders the claims as obvious. The references are considered to be analogous art, thus motivation to combine exists.
Moreover, the Supreme Court pointed out in KSR, “a patent composed of several elements is not proved obvious merely by demonstrating that each of its elements was, independently, known in the prior art.” KSR, 127 S. Ct. at 1741. The Court thus reasoned that the analysis under 35 U.S.C. 103 "need not seek out precise teachings directed to the specific subject matter of the challenged claim, for a court can take account of the “inferences and creative steps that a person of ordinary skill in the art would employ.” Id. at 1741. The Court further advised that “[a] person of ordinary skill is…a person of ordinary creativity, not an automation.” Id. at 1742. Therefore, the claimed invention was obvious to make and use at the time the invention was made and was prima facie obvious.
Conclusion
14. No claims are presently allowable.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to HOPE A ROBINSON whose telephone number is (571) 272-0957. The examiner can normally be reached 9-5pm on Monday to Friday.
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/HOPE A ROBINSON/Primary Examiner, Art Unit 1652