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 .
Continued Examination Under 37 CFR 1.114
A request for continued examination under 37 CFR 1.114, including the fee set forth in 37 CFR 1.17(e), was filed in this application after final rejection. Since this application is eligible for continued examination under 37 CFR 1.114, and the fee set forth in 37 CFR 1.17(e) has been timely paid, the finality of the previous Office action has been withdrawn pursuant to 37 CFR 1.114. Applicant's submission filed on December 8, 2025 has been entered.
Claim Status
Claims 10, 14-21 and 24-26 are withdrawn from further consideration pursuant to 37 CFR 1.142(b) as being drawn to a nonelected species, there being no allowable generic or linking claim.
Claims 1-2, 4-5, 8, and 13 are under consideration in this office action.
Withdrawn Rejections
The rejection of claims 1-2, 4-5, 8, and 13 under 35 U.S.C. 112(b) as being indefinite are withdrawn in view of applicant’s amendment.
New Objections/Rejections
Claim 1 objected to because of the following informalities: the abbreviation CCL3, as used in line 6, is not defined. Including CCL3 in line 5 after “ligand 3” would be sufficient to overcome this objection.
Claim Rejections - 35 USC § 112(d)
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 8 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. Claim 8 includes the limitation wherein the CCL3 is modified to reduce aggregation. Claim 1, from which claim 8 is dependent, includes the limitation wherein the CCL3 comprises an Asp26<Ala substitution. This substitution is known in the art to reduce aggregation in CCL3 (Hunter et al, pg 4407, column 2, paragraph 3, see IDS from 7/7/2021, NPL 13). Thus, the limitation of claim 8 broadens the scope of claim 1 to include any modification of CCL3 that decreases aggregation.
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.
Maintained Rejections
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.
Claims 1, 8, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over US 6,399,078 (“DeVico”) in view of Hunter et al, published December 15, 1995.
DeVico teaches compositions and methods for treating bacterial infection, including Staphylococcus aureus, by administering the immunomodulator MIP-1a/CCL3 (column 9, ln 1-5; column 10, ln 2), as required by claim 1. The compound can be administered systemically or topically (column 28, ln 41-45). While Devico does not explicitly identify MIP-1a by its alternative name CCL3, it is known in the art that the MIP-1a protein was renamed CCL3 in 2000, as evidenced by Menten et al (see IDS from 9/8/2022) (pg 457, “Nomenclature of MIP-1”).
With regards to Methicillin-resistant Staphylococcus aureus (MRSA), as in claim 1, it is the Office’s position that this species within the Staphylococcus genus can be at once envisaged from the prior art because the species within this genus (e.g. MRSA and non-MRSA strains of S. aureus) are sufficiently limited and well delineated (i.e. two options); see MPEP 2131.02(III) and In re Petering (wherein the courts determined that a reference describing a generic formula encompassing about 20 compounds was found to anticipate each of the 20 species without specifically naming them).
DeVico does not teach an Asp>26Ala substitution of CCL3 to reduce aggregation, as required by claim 1.
Hunter et al teaches a variant of human MIP-1alpha (i.e. CCL3) that carries a single amino acid substitution of Asp26>Ala (pg 4400, column 2, ln 11-12), as in instant claim 1. This variant has a reduced tendency to form large polymers at physiologic pH and ionic strength, which greatly increases solubility, thereby facilitating production and clinical formulation (pg 4400, column 2,ln 12-15). This modification is associated with decreased aggregation (pg 4407, column 2, paragraph 3), as in instant claim 8.
As Hunter et al teaches a formulation of CCL3 with decreased aggregation, it would have been obvious to one of ordinary skill in the art to apply the amino acid substitution taught by Hunter in the method of DeVico and have a reasonable expectation of success. The motivation comes from the Hunter reference, which teaches that the genetically engineered variant of MIP-1a has “dramatically improved pharmaceutical properties” without affecting in vitro assessed biologic function (pg 4407, column 2, paragraph 4). One would have been motivated to combine these references because of the art recognized need to generate stable pharmaceutical formulations for the treatment of microbial infection related to cytokine receptor interactions. Further, the artisan has good reason to pursue the known options within their technical grasp to obtain predictable results. Such would amount to the combining of prior art elements according to known methods to achieve predictable outcomes.
Claims 1-2, 4-5, 8, and 13 are rejected under 35 U.S.C. 103 as being unpatentable over DeVico in view of Hunter et al as applied to claims 1, 8, and 13 above, and further in view of US 2016/0346354, published December 1, 2016 (“Heslet”; see IDS from 7/7/2021.
The teachings of Devico in view of Hunter et al are discussed above. These references do not teach a method of treating an infection at a surgical site or in a subject that is a diabetic with an immunomodulator nor do they teach a method further comprising administration of an antibiotic.
Heslet teaches a method for the treatment of infection by administering a pharmaceutical composition comprising the immunomodulator GM-CSF and the antibiotic fosfomycin, as in claim 4. GM-CSF may be used for the treatment of wound caused by surgery [0144], as in the wound on instant claim 2; further, this composition may be used for the treatment of lesions caused by diabetes mellitus [0144], as in claim 5. The composition may be applied topically ([0119],[0121],[0133]), which reads on instant claim 13.
Given that Devico in view of Hunter et al teach a method of treating MRSA infection with CCL3 with Asp>26Ala amino acid substitution, and further given that Heslet teaches a method of treating an infection at a surgical site or a lesion related to diabetes mellitus with an immunomodulator and an antibiotic, it would have been obvious to one of ordinary skill in the art at the time of filing to substitute CCL3 of Devico for the immunomodulator of Heslet in the method of Heslet and arrive at the presently claimed invention. Since Devico teaches treatment of MRSA, an ordinary artisan would have been able to readily conceive a method of treating a MRSA infection at a surgical site of diabetes mellitus related wound. This is because the artisan has good reason to pursue the known options within their technical grasp to obtain predictable results. Such would amount to the substitution of one functionally equivalent element for another (i.e. CCL3 of Devico and the GM-CSF of Heslet) to obtain predictable results.
Response to Arguments
Applicant's arguments filed November 6, 2025 have been fully considered but they are not persuasive. Applicant traverses the rejection under 35 U.S.C. 103, asserting that DeVico disparages the use of BB-10010 and one of ordinary skill in the art would have avoided this treatment (remarks, pg 6). However, DeVico references phase I study of BB-10010 directed to the treatment of subjects infected in HIV and offers no teaching away for bacterial infections (column 6, ln 30-42). Applicant asserts that, based on the teachings DeVico, there is no reasonable expectation of successfully using CCL3 in the treatment of bacterial infection (remarks, pg 9). When considering a prima facie case of obviousness, the prior art is presumed enabled; when the reference relied on expressly makes obvious all the elements of the claimed invention, the reference is presumed to be operable (MPEP 2121.I). However, “applicant must look to the whole reference for what it teaches. Applicant cannot merely rely on the examples and argue that the reference did not teach others.” In re Courtright, 377 F.2d 647, 153 USPQ 735,739 (CCPA 1967).
The assertion that embodiments directed to ligand binding molecules, such as glycosaminoglycan, to form receptor ligand-containing antagonist complexes teach away from using a single therapeutic for the treatment of an infection (remarks, pg 6) does not negate a finding of obviousness under 35 USC 103, since a preferred embodiment, such as an example for glycosaminoglycan, is not controlling. Rather, all disclosures “including unpreferred embodiments” must be considered. In re Lamberti 192 USPQ 278, 280 (CCPA 1976) citing In re Mills 176 USPQ 196 (CCPA 1972). Therefore, it would have been obvious to one of ordinary skill in the art to administer intravenously CCL3 for the treatment of infection, given that Devico teaches that receptor ligands, like CCL3, can be used to treat diseases or conditions dependent upon an infectious agent, such as Staphylococcus aureus.
Arguments related to the nonobviousness of using the CCL3 having an Asp26>Ala substitution in a method of treating an infection are not persuasive, because applicant has not provided any working examples that CCL3 with an Asp26>Ala is efficacious in the treatment of wounds. Rather, applicant provides only evidence that unmodified CCL3 controls infection (see Figure 2). Given the lack of working examples in the disclosure regarding the efficacy of the modified CCL3 in wound healing, a 35 U.S.C. 112(a) scope of enablement rejection was considered. Since the state of the art suggests that unmodified and modified CCL3 would be efficacious, as taught by Devico, a 103 rejection was found to be more appropriate. In the absence of evidence demonstrating that the CCL3 with Asp26<Ala substitution has unexpected properties or its administration is associated with unexpected results, including unexpected efficacy, the 103 rejection is maintained. Applicant’s argument that the references do not teach the claimed method does not address the fact that the combination of references provided good reason to select the peptide species in the treatment of infection and wound healing. It is the examiner’s position that the evidence of obviousness outweigh the case for unpredictability.
Conclusion
No claim is allowed.
Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER BENAVIDES whose telephone number is (571)272-0545. The examiner can normally be reached M-F 9AM-5PM (EST).
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, Jeffrey Stucker can be reached at (571)272-0911. 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.
Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675 Any inquiry concerning this communication or earlier communications from the examiner should be directed to JENNIFER BENAVIDES whose telephone number is (571)272-0545. The examiner can normally be reached M-F 9AM-5PM (EST).
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, Jeffrey Stucker can be reached at (571)272-0911. 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.
Jennifer Benavides
Examiner
Art Unit 1675
/JENNIFER A BENAVIDES/Examiner, Art Unit 1675