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 .
Status of the application
Receipt of applicant’s remarks and claim amendments filed on 09/08/2026 are acknowledged.
In light of claim amendments, previous 112(b) and 102 rejections are withdrawn.
However, applicants’ arguments for the previous 103 rejection are found not persuasive. Accordingly, the rejection is maintained and modified to address claim amendments. Please see the examiners response to applicants arguments below.
Response to Arguments
(i) Applicants’ argue that nowhere does Hodges teach or suggest combining citrate and phosphate together for use as a buffer system, hence the alleged pH combination is not taught or suggested as well, and would not have been achieved by one skilled in the art.
Rejection already acknowledged that Hodges is silent on claimed buffer system. However, Hodges suggested buffers, such as citrate and phosphate. It is common practice in the art that buffer with a desired pH can be achieved by combination of buffers. For example, citrate buffer pH range from 3 to 6.2, whereas phosphate range from 5.8 to 8. The combination can range from 3 to 8, preferably 4 to 7 etc. So, skilled person in the art would determine suitable pH range for the peptides through a routine experimentation.
(ii) Applicants argue that the mass concentration range of antimicrobial peptide disclosed by Hodges encompasses a substantially broader range, spanning 500,000-fold compared with the 100-fold span of 0.1% to 10% as recited in amended claim 1. Thus the Examiner's characterization that the range is very broad in both cases is inaccurate. The broad range of Hodges does not teach or suggest the much narrower range recited.
Hodges provided enough guidance on the concentrations of their antimicrobial peptides. It is obvious to choose suitable concentration range from the established broad range, since the peptides show antimicrobial activity at wide concentration range.
(iii) Applicants argue that the examiner has not identified any teaching from Rowe regarding an antimicrobial peptide liquid composition wherein the buffer system is a disodium hydrogen phosphate-citric acid buffer system as recited in amended independent claim 1 and new independent claim 27. The Examiner merely points to pages 424-428 of Rowe without providing any reasoning as to how the claimed invention is obvious over Hodges and Rowe.
The purpose of Rowe is to show mannitol and its property as a stabilizer and an excipient.
(iv) Applicants argue that the present application shows surprising results further supporting the nonobviousness of the claimed invention.
Both examples 2 and 4 show stabilization of peptides and their properties using the disodium hydrogen phosphate-citric acid buffer system, but fails to compare with any other buffer systems, to show or prove the advantage of claimed buffer system.
Claim Rejections - 35 USC § 103
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 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 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 of this title, 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 set forth in Graham v. John Deere Co., 383 U.S. 1, 148 USPQ 459 (1966), that are applied 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.
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.
Claims 1-2, 4-7, 11, 13, 15-27 are rejected under 35 U.S.C. 103 as being unpatentable over Hodges (US2009/0005300A1) in view of Rowe (Handbook of Pharmaceutical Excipients, 2009, Edited by Rowe, pages 424-428).
For claims 1-2:
Hodges teaches antibacterial peptides [see Table 1] and specifically sequences represented by SEQ ID NO: 4 and 25, which reads applicants antibacterial peptides represented by the recited general formula.
Hodges discloses that their antimicrobial peptides can comprise from 0.0001% to 50% by weight of such compositions [see 0029].
Hodges further teaches that the concentration of peptides are generally in the range of about 0.001 mg/kg to about 100 mg/kg and preferably from about 0.001 mg/kg to about 1 mg/kg final concentration are administered per day to an adult in any pharmaceutically acceptable carrier [see 0040] and in the Fig. 9, it ranges from 8 mg/mL to 500 mg/mL.
Hodges further teaches that the peptides are to be used as antimicrobial agents, they can be formulated, for example, in buffered aqueous media containing a variety of salts and buffers. Examples of the salts include, but are not limited to, halides, phosphates and sulfates, e.g., sodium chloride, potassium chloride or sodium sulfate. Various buffers may be used, such as citrate, phosphate, HEPES, Tris or the like to the extent that such buffers are physiologically acceptable to the host that is being treated [see 0036 and 0134].
Differences between Hodges and instant claims are as follows:
(i) Hodges is silent on representing the concentrations of peptides in percentages in the composition.
(ii) Hodges is also silent on disodium hydrogen phosphate-citric acid buffer system.
With regard to (i) of above, it appears that applicants claimed concentration ranges overlap with the concentration ranges of Hodges, since range is very broad in both cases. Applicants are requested to incorporate or provide the actual amount range in the claims or amount in mg/mL or mg/kg for the recited percentage amounts, which helps in understand the claimed invention.
Even if, range does not overlap, still claims are obvious in light of established case law, see below:
Generally, differences in concentrations of components of a formulation will not support the patentability of subject matter encompassed by the prior art. Such formulations are results-effective variables which can be optimized. In in re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Aller, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
With regard to (ii) of above, though Hodges silent on claimed buffer system, but Hodges suggested buffers, such as citrate and phosphate. Desired pH can be achieved by combination of buffers. For example, citrate buffer pH range from 3 to 6.2, whereas phosphate range from 5.8 to 8. The combination can range from 3 to 8, preferably 4 to 7 etc. So, skilled person in the art would determine suitable pH range for the peptides through a routine experimentation.
Therefore, claims are obvious over the teachings of Hodges.
For claim 4:
Hodges teaches antibacterial peptides represented by SEQ ID NO: 4 and 25, which are identical to applicants claimed SEQ ID NOs: 3 and 4 [see Table 1].
For claim 5:
Hodges teaches that various excipients or other additives may be used, where the peptides are formulated as lyophilized powders, for subsequent use in solution. The excipients may include various polyols, inert powders or other extenders [see 0037].
For claim 6:
Hodges teaches pH of 7, but silent on claimed pH range from 3.5 to 5.5. However, Hodges suggested buffers, such as citrate and phosphate. Citrate buffer pH range from 3 to 6.2, whereas phosphate range from 5.8 to 8. So, the combination reads applicants claimed range. Also, a skilled person in the art would determine suitable pH range for the peptides through a routine optimization, since it is one of the critical step to stabilize a peptide in a composition in addition to other excipients.
For claim 7:
Hodges teaches solution form for their peptide composition [see 0037, 0043 and claim 28].
For claim 11:
Hodges teaches pharmaceutical composition in solution form for their peptides [see Abstract, 0028, 0029, 0037, 0043 and claim 28].
For claim 13:
Hodges further teaches a method of treating a patient in need of therapy comprising administering to the patient a peptide compound of the invention. The invention provides a method of treating a microbial infection. In a particular embodiment, the microbial infection involves one or more of a bacterium, a virus, a fungus, or a protozoan. [See 0013].
For claim 15:
Hodges teaches formulation comprising antimicrobial peptides in buffer solutions and can comprise from 0.0001% to 50% by weight of such compositions, and composition further comprises detergent, which enhance antibacterial characteristics of peptides [see 0029].
The above interpreted as a method of preparation of antimicrobial composition.
For claims 16-17:
Hodges teaches that their antimicrobial peptides can comprise from 0.0001% to 50% by weight of such compositions [see 0029].
For claims 18-20:
Ion concentration is interpreted as ionic strength of composition. Hodges teaches phosphate buffer containing 100 mM KCl [see 0018], which is nothing but ionic strength of buffer. If it is concentration of buffer, then Hodges teaches 50 mM of phosphate buffer [see 0045], which reads claim 18. Hodges silent on 0.02 and 0.015 M ion concentration of buffer.
However, concentration of a given component in a composition is result effective variable, because a skilled person in the art would determine suitable concentration ranges through a routine experimentation, which is common practice in the art. Also, generally, differences in concentrations of components of a formulation will not support the patentability of subject matter encompassed by the prior art. Such formulations are results-effective variables which can be optimized. In in re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Aller, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
For claims 21-23:
Hodges teaches that various excipients or other additives may be used, where the peptides are formulated as lyophilized powders, for subsequent use in solution. The excipients may include various polyols, inert powders or other extenders [see 0037]. Claimed mannitol is a species for polyol. So, polyol from the teachings of Hodges embraces mannitol.
In addition, mannitol is well kwon and common as excipient in formulations because of its advantages [see review article by in Handbook of Pharmaceutical Excipients, 2009, Edited by Rowe, pages 424-428], and therefore, one would be motivated to include mannitol as an excipient in the formulations. With regard to concentrations, concentration of a given component in a composition is result effective variable, because a skilled person in the art would determine suitable concentration ranges through a routine experimentation, which is common practice in the art. Also, generally, differences in concentrations of components of a formulation will not support the patentability of subject matter encompassed by the prior art. Such formulations are results-effective variables which can be optimized. In in re Boesch, 617 F.2d 272,276, 205 USPQ 215, 219 (CCPA 1980), it was held that "discovery of an optimum value of a result effective variable in a known process is ordinarily within the skill of the art." Further, in In re Aller, 220 F. 2d454, 456, 105 USPQ 233,235 (CCPA 1955) the courts maintained that: "Where the general condition of a claim are disclosed in the prior art, it is not inventive to discover the optimum or workable ranges by routine experimentation." As formulating optimal compositions for medicaments is routine in the art of pharmacology, the claims are considered to be prima facie obvious.
For claim 24:
Hodges teaches antibacterial activity against various bacteria with their antibacterial peptides [see Tables 7-12], wherein some are methicillin-resistant strains.
For claim 25:
See For claim 23 above.
For claim 26:
See For claim 1, For claim 4, For claim 6, For claims 18-20 and For claim 23 above.
For claim 27:
See For claims 1-2 above.
Based on the above established facts from the cited prior art, it appears that all the claimed elements, i.e, applicants individual components in the composition and their use in treating post-surgical pain, were known in the prior art, and one skilled person in the art could have combined the elements as claimed by known relationships, with no change in their respective functions, and the combination would have yielded predictable results to one of ordinary skill in the art.
The motivation to modify and combine the art can arise from the expectation that the prior art elements will perform their expected functions to achieve their expected results when combined for their common known purpose. See MPEP 2144.07. Therefore, it would have been obvious to one of ordinary skill in the art before the effective filing date of the claimed invention by taking the advantage of the teaching of the above cited reference and to make the instantly claimed antimicrobial peptide liquid composition with a reasonable expectation of success.
Conclusion
THIS ACTION IS MADE FINAL. Applicant is reminded of the extension of time policy as set forth in 37 CFR 1.136(a).
A shortened statutory period for reply to this final action is set to expire THREE MONTHS from the mailing date of this action. In the event a first reply is filed within TWO MONTHS of the mailing date of this final action and the advisory action is not mailed until after the end of the THREE-MONTH shortened statutory period, then the shortened statutory period will expire on the date the advisory action is mailed, and any nonprovisional extension fee (37 CFR 1.17(a)) pursuant to 37 CFR 1.136(a) will be calculated from the mailing date of the advisory action. In no event, however, will the statutory period for reply expire later than SIX MONTHS from the mailing date of this final action.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to SUDHAKAR KATAKAM whose telephone number is (571)272-9929. The examiner can normally be reached 8:30 am to 5 pm.
Examiner interviews are available via telephone, in-person, and video conferencing using a USPTO supplied web-based collaboration tool. To schedule an interview, applicant is encouraged to use the USPTO Automated Interview Request (AIR) at http://www.uspto.gov/interviewpractice.
If attempts to reach the examiner by telephone are unsuccessful, the examiner’s supervisor, Melissa Fisher can be reached at 571-270-7430. The fax phone number for the organization where this application or proceeding is assigned is 571-273-8300.
Information regarding the status of published or unpublished applications may be obtained from Patent Center. Unpublished application information in Patent Center is available to registered users. To file and manage patent submissions in Patent Center, visit: https://patentcenter.uspto.gov. Visit https://www.uspto.gov/patents/apply/patent-center for more information about Patent Center and https://www.uspto.gov/patents/docx for information about filing in DOCX format. For additional questions, contact the Electronic Business Center (EBC) at 866-217-9197 (toll-free). If you would like assistance from a USPTO Customer Service Representative, call 800-786-9199 (IN USA OR CANADA) or 571-272-1000.
SUDHAKAR KATAKAM
Primary Examiner
Art Unit 1658
/SUDHAKAR KATAKAM/Primary Examiner, Art Unit 1658
Prosecution Insights